The Effects of Two Analgesic Balm Applications on Pain and Psychosocial Factors
Related to Injury
A thesis presented to
the faculty of
the College of Health Sciences and Professions of Ohio University
In partial fulfillment
of the requirements for the degree
Master of Science
Leigh T. Spring
August 2013
© 2013 Leigh T. Spring. All Rights Reserved
2
This thesis titled
The Effects of Two Analgesic Balm Applications on Pain and Psychosocial Factors
Related to Injury
by
LEIGH T. SPRING
has been approved for
the School of Applied Health Sciences and Wellness
and the College of Health Sciences and Professions by
Brian G. Ragan
Assistant Professor of Athletic Training
Randy Leite
Dean, College of Health Sciences and Professions
3
Abstract
SPRING, LEIGH T., M.S., August 2013, Athletic Training
The Effects of Two Analgesic Balm Applications on Pain and Psychosocial Factors
Related to Injury
Director of Thesis: Brian G. Ragan
Problem: Current clinical trials regarding the effectiveness of analgesic balms, in
reducing pain, are inconclusive. Several studies using animal models have supported the
effectiveness of analgesic balms. One issue with some of the current human studies is the
application method of applying the analgesic balm directly over the painful area. This
method only utilizes part of the available skin to cause an effect potentially not allowing
for optimal pain relief. Methods: Single-blinded randomized clinical trial. Women (N=
19; ages 18-40) were recruited from southeastern Ohio and placed into a placebo group,
dermatomal application group, and a painful area application group by covariate adaptive
randomization. Baseline and 2 week testing was done using PROMIS computer adaptive
testing for anger, anxiety, depression, pain interference, and pain behavior. Conclusions:
There was a significant interaction (P < .05) between baseline and 2 weeks for
depression. This was found in the placebo group where depression scores increased.
There was no significant interaction between baseline and 2 weeks for anger, anxiety,
pain interference, and pain behavior. This suggests that analgesic balms do play a role in
decreasing psychosocial factors related to injury.
4
Dedication
This thesis is dedicated to my wonderful parents, Brian and Kim, who have helped me
throughout this entire process, as well as many other family and friends.
.
5
Acknowledgments
I would like to thank Ari-Med Pharmaceuticals for partially funding this research
by donating analgesic balm. I would also like to thank the College of Health Sciences and
Professions for the student research grant.
I would also like to thank my advisor Dr. Brian Ragan for his help throughout the
past two years, and my research partner, Ben Rockwell. Thank you to my committee
members Drs. Jeff Russell and Chad Starkey.
Lastly, thank you to my wonderful parents, Brian and Kim, family, and friends.
You have been a huge help throughout the past two years and have always been there to
support me.
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Table of Contents
Page
Abstract…………………..………………………………………………………………..3
Dedication……………….…..……………………………………………………………..4
Acknowledgements…….…..………………………………………………………………5
List of Tables……….…….………………………………………………………………...9
List of Figures………….………………………………………………………………….10
Chapter 1: Introduction…………………………………………………………………...11
Statement of the Problem………………………………………………………....12
Purpose…………………………………………………………………………....13
Significance of the Study…………………………………………………..……..13
Research Questions…………………………………………………………….....14
Null Hypothesis…………………………………………………………………...15
Dependent Variables……………………………………………………………....16
Independent Variables……………………………………………………………..16
Delimitations…………………………………………………………………..…..17
Limitations…………………………………………………………………..……..17
Definition of Terms……………………………………………………………..…18
Chapter 2: Literature Review…………………………………………………………...….20
Pain…………………………………………………………………………………20
Nociception…………………………………………………………………...……20
Pain Modulation……………………………………………………………………24
Dermatomes……..…………………………………………………………………25
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Psychosocial Factors…………………………………………….……………….26
Analgesic Balms…………………………………….……………………………28
Anterior Knee Pain……………………………………………………………….31
Chapter 3: Methods………………………………………………………………………34
Design and Setting……………………………………………………………….34
Participants………………………………………………………………………34
Instruments………………………………………………………………………38
Procedure………………………………………………………………………...41
Data Analysis…………………………………………………………………….43
Chapter 4: Results………………………………………………………………………..44
Chapter 5: Discussion……………………………………………………………………46
Depression……………………………………………………………………….46
Other Psychosocial Factors……………………………………………………...47
Pain……………………………………………………………………………….48
One Application Versus Multiple Applications…………………………………49
Timing of Application…………………………………………………………...50
Limitations……………………………………………………………………….51
Conclusion……………………………………………………………………….52
References………………………………………………………………………………..54
Appendix A: Recruitment Flyer………………………………………………………….61
Appendix B: Informed Consent Form……………………………………….…………...62
Appendix C: Screening Questionnaire……………………………………..…………….66
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Appendix D: PROMIS Anxiety Long Form…………………………………………….72
Appendix E: PROMIS Anger Long Form……………………………………………….75
Appendix F: PROMIS Depression Long Form………………………………………….78
Appendix E: PROMIS Pain Interference Long Form……………………………………81
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List of Tables
Page
Table 1: Participant Demographics ............................................................................. 35
Table 2: Distribution of Groups by Covariates ............................................................ 44
Table 3: Descriptive Statistics ..................................................................................... 45
10
List of Figures
Page
Figure 1: Flow chart of methods ................................................................................. 37
Figure 2: Home exercise log ....................................................................................... 40
Figure 3: Daily application log.................................................................................... 41
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Chapter 1: Introduction
Pain is caused by actual or potential tissue damage and involves sensory and
emotional components.1 Nociceptors sense painful stimuli and generate impulses. These
impulses are carried by Aδ and C fibers to the dorsal horn where they synapse with
second order neurons. These neurons transmit the impulse up the anterolateral system to
third order neurons in the thalamus. From the thalamus the impulse is sent to fourth order
neurons in sensory cortex where the body interprets the impulse as pain and reacts. It is
also in the sensory cortex that emotions are associated with pain.
Since pain contains an emotional component, there are psychological responses
that occur with injury. Some emotional responses that typically occur with injury are
anger, anxiety, boredom, frustration, fatigue, tension, and depression.2 Previous research
has shown that “emotions such as depression, anger, fear, tension, disgust, anxiety, and
panic . . . can exacerbate the pain of the injury.”3( p354) This thesis focused on depression,
anger, and anxiety.
Anger, anxiety, and depression can all be reduced with physical activity.4,5-12 Pain
from an injury can cause an individual to become less active. Once pain is decreased then
physical activity can resume allowing for the feelings of anger, anxiety, and depression to
subside. One possible way to decrease the pain would be from the application of an
analgesic balm.
Analgesic balms, also called topical analgesics, are creams, gels, ointments, or
patches that are applied to the skin (topical) and provide pain relief (analgesic). Analgesic
12
balms are inexpensive, easy to apply, and non-time consuming, allowing the person to
return to activity or exercise sooner.
Typically analgesic balms are applied following manufacturer’s instructions,
which is over the painful area; however, this does not allow for maximum afferent input.
By applying the analgesic balm over an entire dermatome, more skin would be covered,
thereby activating more sensory neurons. This could potentially allow for greater pain
relief. Applying the analgesic balm using the dermatomal application method activates
both aspects of pain modulation: ascending and descending.
Anterior knee pain (AKP) is a common complaint; 25% of patients reporting to
sports medicine clinics with symptoms consistent with AKP.13,14,15 The majority of these
patients are women.16,17 There are many underlying factors that can lead to AKP that are
typically treated with rehabilitation to correct the issues. Rehabilitation can sometimes be
expensive and is often time consuming. A possible alternative to attending rehabilitation
sessions would be the analgesic balm application used in conjunction with an at-home
rehabilitation program. Grant, Mohtadi, Maitland, and Zernicke18 found that a
“minimally supervised at-home rehabilitation program was more effective in achieving
acceptable knee range of motion 3 months post-op than a standard physical therapy
program.
Statement of the Problem
Current clinical trials regarding the effectiveness of analgesic balms in reducing
pain are inconclusive. Several studies using animal models have supported the
effectiveness of analgesic balms. One issue with some of the current human studies is the
13
application method of applying the analgesic balm directly over the painful area. This
method only utilizes part of the available skin to cause an effect, potentially not allowing
for optimal pain relief.
Purpose
The purpose of this thesis was to evaluate how two analgesic balm application
methods affect pain and psychosocial factors related to injury such as anxiety, anger, and
depression. While this thesis was not looking at the neurophysiological aspects, it was a
patient-centered randomized clinical trial. Thus, the specific aims were:
1. To determine whether the application of menthol, over a period of time, will
decrease anger, anxiety, and depression associated with anterior AKP.
2. To determine whether the application of menthol, over a period of time, will
decrease pain associated with AKP.
3. To determine whether a dermatomal application method, over a period of
time, will decrease anger, anxiety, and depression better than applying the
analgesic balm over the painful area.
4. To determine whether a dermatomal application method, over a period of
time, will decrease pain better than applying the analgesic balm over the
painful area.
Significance of the Study
This thesis intended to provide support that analgesic balms truly work to provide
pain relief, thus decreasing psychosocial factors that accompany injuries. With support
that pain reduction occurs with analgesic balm application, athletic trainers (ATs) have
14
another method to provide pain relief to athletes. Analgesic balms can be applied outside
of the care of the athletic trainer, allowing for pain reduction at all times. This thesis also
intended to determine that a dermatomal application method will provide greater pain
relief than by following manufacturer’s instructions. Maximizing afferent input could
allow for a more significant reduction in pain and could potentially lead to an overall
change with how analgesic balms are to be applied.
Research Questions
The research questions guiding this study were:
1. Will participants applying an analgesic balm experience a greater decrease in
pain compared to those who apply a placebo?
2. Will participants applying an analgesic balm experience a greater decrease in
anxiety, as it relates to injury, compared to those who apply a placebo?
3. Will participants applying an analgesic balm experience a greater decrease in
anger, as it relates to injury, compared to those who apply a placebo?
4. Will participants applying an analgesic balm experience a greater decrease in
depression, as it relates to injury, compared to those who apply a placebo?
5. Will participants using a dermatomal application method experience a greater
decrease in pain compared to those who follow the manufacturer’s
instructions?
6. Will participants using a dermatomal application method experience a greater
decrease in anxiety, as it relates to injury, compared to those who follow the
manufacturer’s instructions?
15
7. Will participants using a dermatomal application method experience a greater
decrease in anger, as it relates to injury, compared to those who follow the
manufacturer’s instructions?
8. Will participants using a dermatomal application method experience a greater
decrease in depression, as it relates to injury, compared to those who follow
the manufacturer’s instructions?
Null Hypothesis
H01 There is no difference in pain between the analgesic balm groups and the
placebo group.
H02
There is no difference in anxiety between the analgesic balm groups and
the placebo group.
H03
There is no difference in anger between the analgesic balm groups and the
placebo group.
H04
There is no difference in depression between the analgesic balm groups and
the placebo group.
H05
There is no difference in pain between the dermatomal application method
and the manufacturer’s instruction application method.
H06
There is no difference in anxiety between the dermatomal application
method and the manufacturer’s instruction application method.
H07
There is no difference in anger between the dermatomal application
method and the manufacturer’s instruction application method.
16
H08
There is no difference in depression between the dermatomal application
method and the manufacturer’s instruction application method.
Dependent Variables
1. The anxiety of each participant was measured before beginning the study and 2
weeks later.
2. The anger of each participant was measured before beginning the study and 2
weeks later.
3. The depression of each participant was measured before beginning the study and
2 weeks later.
4. Pain interference of each participant was measured before beginning the study
and 2 weeks later.
5. Pain behavior of each participant was measured before beginning the study and 2
weeks later.
Independent Variables
1. The participants underwent a treatment of a menthol-based analgesic balm or a
placebo
a. The participants were assigned to a group where they applied a menthol-based
analgesic balm.
b. The participants were assigned to a group where they applied a placebo.
2. The participants were assigned to a dermatomal application group or a
manufacturer’s instruction group.
17
a. The participants were assigned to a group where they applied a menthol-based
analgesic balm using the dermatomal application method.
b. The participants were assigned to a group where they applied a placebo using
the dermatomal application method.
c. The participants were assigned to a group where they applied a menthol-based
cream following manufacturer’s instructions.
3. The participants completed testing prior to beginning the study and after 2 weeks.
a. The participants underwent baseline testing prior to beginning the study.
b. The participants underwent testing after 2 weeks.
Delimitations
Delimitations of this study included:
1. Participants in this study are women ages 18-40.
2. Participants were free of knee injury or knee surgery for the past 12 months.
3. Participants in this study have patellofemoral pain syndrome (PFPS),
osteoarthritis (OA), or both.
Limitations
Limitations of this study included:
1. Participants must remember to apply the analgesic balm at least once every day.
2. Participants must be compliant when applying the analgesic balm, completing the
application log, and completing the home exercise program.
3. The percentage of menthol used for this study was 16%.
4. Participants must remember to complete the online surveys.
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Definition of Terms
Analgesic balm (topical analgesic). A cream, gel or ointment applied to the skin
(topical) that provides relief from pain (analgesic) without causing a loss in sensation
(anesthetic).
Afferent. Signals sent from the body to the brain.
Counterirritant. Counterirritants are applied to the skin and cause an “irritating”
effect to provide relief from pain.
Dermatomal application. Analgesic balm application method covering a large
area of the skin, not just the painful area.
Dermatome. Area of the skin innervated by cutaneous nerves that come from
specific nerve roots.
Gate control theory. Ascending and descending pain modulation theories
developed by Melzack and Wall in 1965.
Nociception. Neural process of encoding noxious stimuli from actual or potential
tissue damage.
Nociceptors. Sense painful stimuli. Also called “free nerve endings.”
Osteoarthritis (OA). Degeneration of articular cartilage of a joint causing diffuse
anterior knee pain.
Patellofemoral pain syndrome (PFPS). Anterior knee pain not linked to a
specific mechanism or pathology.
Pain. Unpleasant sensory and emotional experience associated with actual or
potential tissue damage.
19
Placebo. A substance, in this case a cream that has no medicine or active
ingredient used with the intent to make the patient believe they are better.
Sensory receptors. Specialized structures that respond to changes in the external
world or stimuli.
20
Chapter 2: Literature Review
This chapter will discuss literature on pain, nociception, and pain modulation as
well as all components that fit into those topics. Dermatomes and the use of a dermatomal
application method will also be discussed. Finally, AKP will be discussed followed by
the psychosocial factors that accompany injuries, especially those associated with chronic
pain.
Pain
Pain is defined as an “unpleasant sensory and emotional experience associated
with actual or potential tissue damage.”1 Since pain consists of an emotional component,
psychosocial factors such as anxiety, anger, and depression manifest with injury. These
psychosocial factors tend to be worse with chronic pain because it affects aspects of daily
life and is often difficult to find relief. The goals of chronic pain management are
reduction of pain and improvement of physical and psychosocial function. 19
Nociception
Nociception is often described as the neural process of encoding noxious stimuli
from actual or potential tissue damage. 1 Pain and nociception are often used
synonymously with one another but are not the same thing. Nociception is the process
that leads to the sensation of pain.
Sensory receptors. Sensory receptors are specialized structures that respond to
changes in the external world or stimuli.20 Sensory receptors can be classified in a few
ways: by the location of the receptor (location of the actual receptor or the activating
stimulus); by the complexity of the structure of the receptor; or, by the type of stimulus
21
activating the receptor. Exteroceptors, interoceptors, and proprioceptors are specific
sensory receptors located in these areas. Exteroceptors are located near or at the surface
of the body. These receptors are sensitive to stimuli outside of the body. Interoceptors are
located inside of the body especially in the viscera and blood vessels. These receptors are
activated by a variety of things that take place within the body. Lastly, proprioceptors,
like interoceptors, respond to stimuli located inside of the body; however, they are
located in skeletal muscles, tendons, ligaments, joints, and other types of connective
tissue.
Sensory receptors can either be classified as simple or complex receptors. 21
Simple receptors are found throughout the body and are in charge of monitoring most of
the general sensory information. Complex receptors are not as plentiful as simple
receptors. They are actually sense organs and make up the special senses such as vision,
hearing, smell, and taste.
These receptors can be activated by many different types of stimuli such as
pressure, chemicals, temperature, light, and pain. These types of sensory receptors are
mechanoreceptors, chemoreceptors, thermoreceptors, photoreceptors, and nociceptors.
Although there are several types of receptors, nociceptors are the focus of this thesis.
Nociceptors, also called free nerve endings, respond to harmful stimuli that cause pain.
These receptors also have subclasses of receptors that respond to pressure, chemicals, and
extreme temperatures eliciting pain.
22
Lamina. The gray matter of the spinal cord can be subdivided in laminae or
“rexed lamina.” There are 10 laminae in the gray matter, extending the entire length of
the spinal cord. Lamina I is located in the dorsal horn and is the most dorsal (posterior)
lamina. Lamina IX is the most ventral (anterior) part of the ventral horn and lamina X
completely surrounds the central canal.21
The lamina most important for this project are laminae I through VI, because
they are all located in the dorsal horn and contain cells that are responsible for receiving
and transmitting signals from sensory afferent fibers. Lamina II is particularly important,
because it contains cells that correspond to the substantia gelatinosa (SG). This particular
group of cells receives information from Aδ and C fibers.21
Sensory Neuron Levels. There are many different types of afferent first order
neurons. Some are small in diameter while others have a large diameter. These fibers may
also be myelinated or unmyelinated. The myelinated fibers transmit their afferent signals
much faster than unmyelinated fibers. Many of these fibers rely on different types of
stimuli for activation. Some are activated by pain, others by touch, and others by changes
in temperature or changes in the muscle itself, such as length and velocity.
Afferent Aδ and C fibers play a large role in this thesis. Both of these fibers are
small in diameter, first order neurons and are responsible for two pain sensations, fast
pain and slow pain. Fast pain results from the activation of myelinated Aδ fibers, sending
sharp, pricking sensations to a localized area. 22 Slow pain is a burning pain which results
from the activation of unmyelinated C fibers. Slow pain often has a slower onset, a longer
duration, and is more generalized than fast pain.22 Aδ and C fibers also transmit
23
sensations of warmth and cold in the skin allowing pain and temperature sensation to
travel along the same pathways. Since menthol binds to cold receptors, the cold signal
will travel along the same pathway as pain. Two signals cannot be transmitted along the
same fibers at the same time, so the cold sensation might cause a decrease in pain as well.
Aβ fibers are also important to this thesis. These first order neurons are large in
diameter and are activated by touch, usually a rubbing sensation. It is thought that as a
larger area is being rubbed, more signals will be transmitted to the “gate” more
frequently, allowing for attenuation of pain. In this case, Aβ fibers will be activated by
rubbing on the analgesic balm or placebo. Even though the placebo contains no actual
active ingredient for pain relief, the rubbing sensation may be enough to elicit a decrease
in pain. The counterirritant of menthol may also activate Aβ. The skin irritation that
occurs after the analgesic balm application causes an activation of the Aβ fibers just like
rubbing the area. These fibers carry this impulse to the “gate” closing it to the impulses
carried by the Aδ and C fibers.
Second order neurons transmit the sensory information from the dorsal horn to the
brain by the anterolateral system. Second order neurons can be classified as wide
dynamic range neurons or nociceptive specific. Wide dynamic range neurons receive
information from the Aβ, Aδ, and C fibers whereas the nociceptive-specific neurons only
respond to noxious stimuli, receiving information from Aδ and C fibers only.
Third order afferents are located in the brain. Once they receive signals from
second order neurons, third order neurons carry information to specific parts of the brain,
typically the thalamus. From the thalamus, the signal is transmitted to fourth order
24
neurons in the sensory cortex. At this time, the body reacts to the stimulus and removes
the body from the noxious stimulus, if possible. This is the time when the psychosocial
factors become noticeable and help explain the role of emotions in the interpretation of
pain.
Pain Modulation
Gate control theory. The gate control theory of pain modulation encompasses
several different mechanisms to aid in the reduction of pain. These mechanisms include
ascending pain modulation and descending pain modulation.
Ascending pain modulation. Aδ and C fibers carry the pain signal to the
substantia gelatinosa (SG). The SG acts as the “gate.” The “gate” is opened and the signal
is transmitted on to the transmission cell (T cell) located in the dorsal horn. From the T
cell, the impulse is then transmitted to higher centers in the brain where the signal is
actually interpreted as pain. Pain is usually felt until some other sensation takes its place
or until the stimulus causing pain is removed.23
In most cases, touch causes the feeling of pain to be diminished. For example, you
hit your elbow on a wall and instantly feel pain. The first thing that usually happens is
you begin to rub the area where the pain is felt and the pain begins to lessen. Touch
sensation is carried along the Aβ fibers which are large diameter afferents. The touch
signal is also transmitted to the SG. When this signal reaches the SG, the “gate” swings
closed, blocking the pain signal and allowing the touch sensation to be sent to the brain.
Since the pain signal can no longer reach the brain, pain decreases.
25
Descending pain modulation. The menthol stimulates thermoreceptors, small
diameter afferent fibers (Aδ and C fibers) that transmit the signal to the spinal cord where
it synapses with second order neurons then to higher level neurons in the brain such as
cerebral cortex. There are several different mechanisms for pain reduction in descending
pain modulation. One mechanism begins with the portion of the cerebral cortex
stimulating the periaqueductal gray (PAG). The PAG activates neurons in the raphe
nucleus, a portion of the medulla.24 The raphe nucleus then relays the signal back down
the body via the dorsolateral tract to the dorsal horn where encephalin interneurons are
activated, closing the “gate.” Afferent traffic is reduced and pain is decreased. 24 Another
mechanism is when fibers located in the raphe nucleus release serotonin which directly
inhibits tract cells and activates enkaphalin interneurons and closing the “gate.”19 Another
mechanism of descending pain modulation is when fibers from the locus ceruleus trigger
the release of norepinephrine. Norepinephrine blocks the transmission of the pain signal,
leading to a decrease in pain.24
Dermatomes
A dermatome is “the area of the skin innervated by the cutaneous branches of a
single spinal nerve.”20(p516) Dermatome regions overlap, not allowing complete numbness
of an area if the spinal nerve is injured. These areas may differ from person-to-person and
from the dermatome maps typically seen. The dermatomes that cross the knee come from
both cervical and lumbar plexuses, the L3-L5 nerve roots. However, the dermatomes of
interest in this study are L3 and a portion of L4, making sure to cover the entire knee.
26
Hilton’s Law states that “any nerve serving a muscle that produces movement at that
specific joint also innervates the joint and the skin over the joint.”20(p516)
Dermatomal Application. When using analgesic balms many people apply it by
following the manufacturer’s instructions, which is directly over the painful area, but this
is not where the pain comes from. Initially, nociceptors are activated by a noxious
stimulus. This impulse is then transmitted to the spinal cord where it synapses with other
neurons and sends the impulse to the brain. The brain is where the impulse is interpreted
by the body as pain. The painful area usually consists of one dermatome and the area of
skin covered is minimal. When the analgesic balm is applied over the painful area,
afferent input will not be maximized and pain will be slightly decreased but not to the
amount it could be.
Ascending and descending pain modulation are ways to decrease pain, as
mentioned in a previous section. Both mechanisms provide pain relief with minimal
afferent traffic inhibition. With the dermatomal application method the amount of skin
covered will be maximized, thereby maximizing afferent input. Both the ascending and
descending mechanisms of pain modulation will provide greater pain relief.
Psychosocial Responses to Injury
Psychosocial responses to injury are normal and can be subdivided into cognitive,
behavioral, and emotional responses. People with injuries usually experience more
psychological distress than people without injuries.25 This thesis focuses on the emotional
responses to injury. Emotions are described as “complex psychophysiological states that
have a quick onset, shot duration, and common cognitive antecedents.”26(p172) According
27
to Wiese-Bjornstal,2 the emotional responses typically seen after an injury are anger,
anxiety, depression, boredom, frustration, fatigue, and tension. Previous research has
shown that “emotions such as depression, anger, fear, tension, disgust, anxiety, and panic
have been shown to create psychophysiological reactions that contribute to and
exacerbate the pain of the injury.”3(p354) Anxiety, anger, and depression are the emotional
responses focused on in this thesis.
Anger can also be linked to injury. Frequently, people are angry after injury
because they become removed from their normal activities such as physical activity or
exercise. Once the ability to exercise reaches preinjury levels, anger may decrease.
Hassmen, Kolvula, and Uutela4 found that people who exercised 2 to 3 days a week or
daily experienced lower anger levels than those people who lived a more sedentary
lifestyle. They also found that women who exercised less regularly had more anger than
males who exercised the same amount. 4 Therefore, decreasing pain and increasing
physical activity could ultimately reduce anger.
Physical inactivity has been linked to the development of anxiety and
depression.5-12 Physical inactivity goes hand in hand with injury. After an injury, pain
occurs and activity decreases. Depression and pain share common neurotransmitters and
a vicious cycle is often created between the two.27 Depression is thought to be 3 to 4
times more likely in people with chronic pain.28 Because activity has decreased, anxiety
and depression are more likely to develop. Once pain has been decreased or eliminated,
activity can resume, thus decreasing anxiety and depression.
28
It is often believed that a disruption of normal levels of norepinephrine, serotonin,
dopamine, growth hormone, and thyroxin can lead to the development of depression. 29
Many of these neurotransmitters are released during the descending portion of pain
modulation. The activation of the descending pain mechanism could potentially reduce
depression without the need for an increase in physical activity.
Overall, pain is the largest contributing factor for causing limited activity. The
pain then leads to the development of psychosocial factors such as anger, anxiety, and
depression. As pain subsides, and normal physical activity is restored, the psychosocial
factors related to the injury will also decrease.
Analgesic Balms
Analgesic balms also called topical analgesics are creams, gels, ointments, or
patches applied to the skin (topical) and provide relief from pain (analgesic) without
causing a loss in sensation (anesthetic). Analgesic balms are relatively safe because there
is little to no risk of long-term complications from prolonged or continued use like their
over-the-counter oral counterparts.30
Many randomized clinical trials have been done, all showing varying results about
the efficacy of analgesic balms in humans. Myrer, Freland, and Fellingham31 conducted a
double-blinded randomized clinical trial on men and women with osteoarthritis. One
group applied an analgesic balm and the other group applied a placebo. No differences in
pain were found between the groups.31
In 1970, White and Sage32 treated delayed onset muscle soreness with an
analgesic balm and a placebo. The results showed that the analgesic balm group
29
experienced greater pain relief than the placebo group. 32 White and Sage33 completed
another study in 1971 using an analgesic balm group and a placebo group. This study was
conducted on participants with osteoarthritis and rheumatoid arthritis. This study also
concluded that the analgesic balm group experienced more pain relief. 33
Studies conducted on cats have shown promise for the effectiveness of analgesic
balms.34,35,36 There are two main classes of analgesic balms: salicylates and
counterirritants. Frequently analgesic balms contain a combination of a salicylate and a
counterirritant.
Salicylates. Salicylates reduce the metabolism of prostaglandins in the periphery,
sensitizing nerve endings at the injury site by the use of cycloxygenase pathways.
Cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2) are the two major pathways in
which salicylates work. COX-1 is found in the blood vessels and COX-2 is triggered by
the need for prostaglandin release or injury and plays a vital role in the inflammatory
process. Nonsteroidal anti-inflammatories (NSAIDs) work to inhibit the actions of these
pathways therefore decreasing signs of inflammation and pain.37
Counterirritants. Counterirritants are applied to the skin and cause an
“irritating” effect to provide relief from pain; however, the exact mechanisms of pain
reduction are not entirely known.38 They are thought to decrease pain in many different
ways. One potential mechanism for pain control is engaging the “gate control” theory.
The a-delta fibers are activated by the rubbing sensation, thereby blocking the pain signal
from reaching the brain. It is also thought that counterirritants actually have no effect at
30
all and are strictly just placebos. In this case people believe the analgesic balm works
because they are told they will experience a reduction in pain.
Capsaicin. Capsaicin is found naturally in red chili peppers and is extracted to be
used as an additive in an analgesic balm. The vanilloid receptor subtype 1 (VR1) resides
on the membrane of a cation channel that contains thermoreceptors and nociceptors,
making it the target of capsaicin.39 Capsaicin mimics the burning sensation of external
heat and the nerves become overwhelmed by the increase in temperature. 40 Prolonged
activation of these neurons depletes one of the body’s many neurotransmitters for pain
and heat, not allowing the body to report pain.
Methyl Salicylate. Methyl salicylate is a combination of a salicylate and a
counterirritant. It is often found as an inactive ingredient in many analgesic balms and is
used in conjunction with active ingredients such as capsaicin or menthol. It is an organic
ester produced by many wintergreen plants. Methyl salicylate is used as a defense
mechanism by these plants to ward off herbivores and certain viruses. Frequently this
product is created commercially and not extracted directly from plants. If created
commercially it is produced by combining menthol and salicylic acid.
Menthol. Menthol is another active ingredient in many analgesic balms and is the
focus of this study. Menthol is found in the oil of many types of mint plants (peppermint),
giving it a distinctive smell. It is commonly used in oral hygiene products,
pharmaceuticals, pesticides, cosmetics, and as a flavoring in many foods. Initially, after
menthol application, a cooling sensation is felt. After a short time, the cooling sensation
will switch to a warm, burning type sensation.
31
Applying menthol stimulates the TRPM8 ion channel leading to an increase in
intracellular Ca2+.41,42 This causes depolarization resulting in the generation of an action
potential.43,44 TRPM8 has been found in small diameter afferent nerves involved in
sensing pain. Menthol is also thought to desensitize C fibers, allowing for a long-term
decrease in nociceptive function and pain.
Overall, menthol does not produce a toxic effect and the risks with its use are
minimal. The risk of experiencing an adverse reaction to the menthol is less likely the
lower the concentration of menthol. The most common adverse effects are skin
irritations, erythema, and burns; however, this is commonly seen in menthol
concentrations of 40% or higher.
Anterior Knee Pain
AKP is a common complaint in orthopedic care with 25% of patients reporting to
sports medicine clinics with symptoms consistent with AKP.13,14,15 There are a couple
groups of people who are at a higher risk of developing AKP: younger and older females.
Younger females are at an increased risk of developing AKP because of increased use. 16
They are involved in more sports and may not take breaks between seasons to allow the
body to rest. Older females are also at a higher risk for developing AKP because of lack
of conditioning, degenerative changes, and previous injuries. 16 Females are more at risk
for developing AKP for many reasons. Some of these reasons include muscle imbalances
or weaknesses, neuromuscular control, trochlear groove width, lower limb alignment or
biomechanics, and Q-angle.
32
People dealing with AKP regularly experience pain when performing many daily
activities. These activities include: squatting, standing after sitting for extended periods
of time, and ascending or descending stairs. Two conditions or syndromes where a
common complaint is AKP are patellofemoral pain syndrome (PFPS) and osteoarthritis
(OA). These two conditions are used as models for this study because of a high incidence
rate among females, allowing for an increased number of potential participants.
Patellofemoral pain syndrome. PFPS is a chronic condition characterized by
pain in the anterior knee that is not linked to a specific mechanism or pathology,
accounting for pain, dysfunction, and time lost from athletic activities, activities of daily
living (ADLs), and instrumental activities of daily living (IADLs). Women have a higher
prevalence of PFPS than men.45
Osteoarthritis. OA is the most common form of arthritis and women are believed
to have a 1.8 times greater risk of developing OA than men.46 OA is characterized by
anterior knee pain, pain with many daily activities, morning stiffness, and the feeling of
the knee “giving way”.47 All structures within the joint are usually affected with OA.
When it comes to the actual knee joint, articular cartilage is lost, remodeling of the bone
occurs, and the joint capsule can become stretched. Many of the muscles surrounding the
knee, especially the quadriceps, can become weak.
There are two main types of OA that affect the knee, patellofemoral and
tibiofemoral. Patellofemoral OA is a common cause of anterior knee pain and disability,
with about half of people with arthritis of the knee joint having patellofemoral OA.48
Tibiofemoral OA is what most people call “osteoarthritis of the knee.” Many people are
33
diagnosed with tibiofemoral OA because its risk factors are more easily understood.
Tibiofemoral is thought to develop from long periods of weight bearing and loading of
the tibiofemoral joint.
34
Chapter 3: Methods
This study will examine the efficacy of two techniques of analgesic balm
applications on pain and psychosocial factors, such as anxiety, anger, and depression, as
they relate to injury. This study will involve two phases of data collection; baseline and
after 2 weeks. This chapter will describe the design of the study, participants involved,
instrumentation, procedures, and data analysis.
Design and setting
This study was a single-blinded randomized clinical trial conducted at Ohio
University and registered on clinicaltrials.gov. Participants were screened, in person, and
signed informed consent forms at the university with the remainder of the testing taking
place at the participants’ residences. All surveys used for data collection were completed
online through the PROMIS assessment center. See Figure 4 for a flow chart of the
study’s methods.
Participants
Recruitment. According to the power analysis, a total of 18 to 21 participants
were used in this study. The participants were separated into three groups: manufacturer’s
instructions for application (n = 7), dermatomal application (n = 6); and, placebo
(control) group (n = 6). Women ages 18 to 40 were recruited from the university and
surrounding area to volunteer for this study by the use of a recruitment flyer and speaking
to classes at the university (see Appendix A). Table 3 contains the demographics for the
participants. Women were chosen as participants for the study because women have a
higher risk for developing AKP.
35
Table 1. Participant Demographics
Demographic
Placebo
Dermatomal Area
Painful Area
Height*
65.50 ± 2.59
64.67 ± 2.16
64.33 ± 3.20
Weight*
159.50 ± 30.29
146.50 ± 55.99
138.17 ± 14.91
*Approximations by participants.
Inclusion and exclusion criteria. Participants were selected for participation in
the study based upon the following criteria: (1) women, (2) between the ages of 18 to 40,
(3) insidious onset of AKP at least 4 weeks in duration, (4) pain of at least a 3 on a 10point scale at the time of enrollment, and (5) report of anterior knee pain during at least
three of the following: during or after activity, prolonged sitting, stair ascent or descent,
or during squatting.
Participants were excluded from the study based upon the following criteria: (1) a
previous traumatic knee injury, within the past 12 months, (2) a previous knee surgery,
within the past 12 months, (3) any dermatologic conditions such as general skin dryness
or redness, eczema, atopic dermatitis, or psoriasis especially over the application area, (4)
open wounds over the area of application, (5) pregnancy, and/or (6) any allergies to any
of the ingredients in the analgesic balm such as menthol, allatonin, aloe barbadensis leaf
juice, carbomer, diisopropyl adipate, eucalyptus globulus leaf oil, glycerin, mentha
piperita (peppermint) oil, methyl salicylate, SD alcohol 40, steareth-2, steareth-21,
thymus vulgaris (thyme) oil, tocopheryl acetate, or triethanolamine. Women who had
been previously diagnosed with OA within the past 12 months were not excluded from
participation.
36
Participants currently taking NSAIDs were not excluded from the study. Instead,
this was used in the randomization process as a covariate. Other covariates used in the
randomization process were age and physical activity. These covariates will be discussed
further in chapter 3 of this thesis.
Prior to beginning to apply the analgesic balm or placebo, participants agreed not
to introduce any new body care products (body lotions, cosmetics, hair care, skin care,
and personal hygiene products).30 All participants signed an informed consent form
approved by Ohio University’s Institutional Review Board (see Appendix B).
Power analysis. Because of a lack of literature, the power analysis is based on a
Cohen scale for small effect size. The effect size was 0.3 to 0.4 with the alpha level at
0.05 and the power at 0.80. According to the power analysis calculation, the total sample
size should be 18 to 21 participants with a minimum of 6 to 7 people in each of the 3
groups. Ideally each group should contain 10 participants because we predicted a 50%
attrition rate due to the longitudinal nature of the study. A repeated measures ANOVA
within-between interaction was used.
37
Register Randomized Clinical Trial
Participant Recruitment
Pre-screening
Inclusion/exclusion criteria
Excluded
Included
Screening
Physical examination/inspection by
the athletic trainer
Excluded
Included
Orientation
(N = 19)
Baseline Testing
PROMIS surveys
Covariate Adaptive
Randomization
Manufacturer’s
Recommendations
Application Group
(N = 7)
Placebo (control)
Group
(N = 6)
2 Weeks
PROMIS surveys
Figure 1. Flow chart of methods.
Dermatomal Application
Group
(N = 6)
38
Instruments
This study used multiple data collection instruments. Prior to beginning the study
participants were screened over the phone to determine inclusion or exclusion from the
study. Participants who passed the initial screening were physically tested and examined
to make sure they had no open wounds or dermatologic conditions over the application
area. The PROMIS anxiety survey, anger survey, depression survey, pain interference
survey, and pain behavior surveys were administered. Participants were also given the
home exercise program log and application log to take with them and complete at home.
Over-the-phone screening and medical questionnaire. This questionnaire was
created as a health history questionnaire. It also served as a way to include or exclude
participants from participation in the study. The participants were asked the questions on
this survey over the phone prior to being included in the study, and again in person to
verify the answers (see Appendix C).
PROMIS anxiety survey. This was a 29-question scale that determined how
anxious a person felt over the past 7 days. It measured sleep disturbances, as well as
physical and emotional effects of anxiety (see Appendix D). The alpha reliability of the
anxiety survey was 0.97. This survey was administered as a computer-adaptive survey.
PROMIS anger survey. This was a 30-question scale that determined an
individual’s anger over the past 7 days. It measured how angry an individual is at others
as well as themselves and their own life. The alpha reliability of the anger survey was
0.96 (see Appendix E). This survey was administered as a computer-adaptive survey.
39
PROMIS depression survey. This was a 28-question scale that determined how
depressed or sad someone felt within the past week (see Appendix F). The anger survey
had an alpha reliability of 0.98.This survey was administered as a computer-adaptive
survey.
PROMIS pain interference survey. This was a 41-question scale that measured
how much pain interfered with activities of daily living over the past 7 days (see
Appendix G). The pain interference survey had an alpha reliability of 0.99. This survey
was administered as a computer-adaptive survey.
PROMIS pain behavior survey. This was a 39-question scale that measured
how one’s behavior changed due to pain over the past 7 days. It measured facial
expressions when the person was in pain as well what the individual did to help relieve
that pain (see Appendix H). The alpha reliability for the pain behavior survey was 0.98.
This survey was administered as a computer-adaptive survey.
Home exercise program log. The home exercise program log (see Figure 5 and
Appendix I) was used by participants to track the strengthening and stretching exercises
they completed.
40
Figure 2. Example of the home exercise log.
Daily application log. The daily application log (see Figure 6 and Appendix J)
was used by participants to record the times they applied the analgesic balm. The log
included the date, four application time slots, time of application, and the pain level at the
time of application. Participants were asked to complete the application log each time
they applied the analgesic balm. The data obtained from the daily application log was
used to determine if the participant experienced pain relief as reflected by fewer numbers
of applications and lower pain levels at the time of application.
41
Figure 3. Example of the daily application log.
Procedure
To participate in the study, participants contacted the researchers to set up a time
for over-the-phone screening to see if they qualified for the study. If participants were
eligible to take part in the study they met with researchers in person, finished the
screening process, and signed an informed consent form. After consent was given,
participants underwent an inspection of the application area to determine that there were
no open wounds or dermatologic conditions, and participants were educated on the
product and placement of the analgesic balm. Participants were educated on both
application methods used in the study and received an email telling them which method
to use. This was done in order to keep researchers blinded on application methods.
42
Baseline testing then took place. Baseline testing consisted of completing computerbased surveys on anger, anxiety, depression, and pain.
Participants were also given 2 weeks worth of cream and folders containing the
daily application log and home exercise program. Participants received daily reminders
through email or text message instructing them to apply the analgesic balm, complete the
application log, and complete the home exercise program.
Prior to baseline testing, participants were assigned a code number for
confidentiality. At this time participants were randomly placed into a group and given a
color (red, blue, or green) that corresponded with the code number. The color linked
participants to the application method they were using. Researchers did not know which
color was linked to which application method until data collection was completed.
After a 14-day period, participants returned the application log and home exercise
program log to researchers. Several days prior to the 2-week time limit, participants
received an email with a link to the surveys. At this time, participants completed
computer-based surveys. They were given 4 days to complete the surveys. If participants
did not have access to a computer or the internet, they could call researchers to set up a
time to come in to use a computer or participants could be asked the questions over the
phone.
Participants received more cream, if needed, and enough forms to last another 2
weeks. After a 28-day period, participants once again returned the application log and
home exercise program log to researchers and surveys were completed. After all
participants had completed the surveys, data was then collected and analyzed. If at any
43
time a participant had a bad reaction to the cream, they were instructed to inform the
investigators and seek medical attention.
Data analysis
The independent variables for this study were treatment, application method, and
time. The dependent variables for this study were anxiety, anger, depression, pain
interference, and pain behavior. Data was compiled and put into SPSS 18.0. The data was
then analyzed using a repeated measures ANOVA. Each of the PROMIS surveys were
analyzed to determine which method of analgesic balm application rendered the best
results after a 2-week period.
Covariate adaptive randomization. Covariate adaptive randomization is the
process of placing participants into groups by certain variables or covariates.
Randomization was done in order to remove bias from the groups and allowed
participants, with the same covariates to be dispersed into different groups. There is one
issue with covariate adaptive randomization in that the group assignments can become
predictable.49
The participants were randomly assigned to a group by the use of three covariates:
age, physical activity, and usage of pain medications. Each covariate has subcategories.
Age has three subcategories: 18-25, 26-34, and 34-40. Physical activity has two
subcategories: meets ACSM physical activity guidelines and does not meet ACSM
guidelines. The last covariate is the usage of pain medications. This covariate also has
two subcategories: currently taking pain medications, or not currently taking pain
medications.
44
Chapter 4: Results
This chapter will present the results from the randomized clinical trial. Participant
data at baseline and 2 weeks will be presented as well as the statistics.
Covariate adaptive randomization was done to provide equality to the 3 groups.
Table 4 presents the breakdown of groups by covariates. No statistical tests were
performed to ensure similarity because of the small sample size (cell n < 5). The
descriptive statistics for the 5 dependent variables at baseline and 2 weeks, for each of the
3 groups are presented in Table 5. There was a significant interaction (F(1,16) = 4.99, P
< .05) for depression. The significant difference was with the placebo group over time.
There were no significant interactions (P > .05) for anger, anxiety, depression, pain
interference, and pain behavior.
Table 2. Distribution of Groups by Covariates
Age (yrs)
ACSM Guidelines*
Pain Medications
Placebo
Dermatomal
Area
Painful Area
18-25
5
6
5
26-33
0
0
1
34-40
1
0
1
Met
5
5
6
Did not meet
1
1
1
Currently Taking
3
3
5
Not Taking
3
3
2
*American College of Sports Medicine guidelines: 30-60 minutes of moderate-intensity exercise
(5 days per week) or 20-60 minutes of vigorous-intensity exercise (3 days per week).
45
Table 3. Descriptive Statistics
Painful Area
Placebo
Dermatomal Area
Baseline
2 Weeks
Baseline
2 Weeks
Baseline
2 Weeks
Anger
53.57 ± 6.87
52.57 ± 8.40
53.33 ± 9.27
50.83 ± 4.49
55.83 ± 7.86
51.17 ± 3.37
Anxiety
58.43 ± 6.58
59.14 ± 7.15
52.83 ± 6.71
51.33 ± 4.37
57.33 ± 7.12
54.50 ± 2.66
Depression*
49.29 ± 3.04
50.14 ± 3.88
48.17 ± 4.58
53.50 ± 3.83
52.17 ± 6.01
48.83 ± 1.60
Pain
Interference
52.43 ± 3.46
53.86 ± 4.06
53.67 ± 2.88
52.17 ± 8.79
57.30 ± 3.03
51.17 ± 6.31
Pain Behavior
54.29 ± 2.87
53.00 ± 4.14
55.83 ± 2.99
54.50 ± 6.53
56.00 ± 2.19
54.17 ± 1.17
*The depression score showed a significant difference between baseline and 2-week follow-up (P < .05), ie, the depression
score increased (worsened) in the placebo condition in contrast to the two analgesic balm treatment groups where depression
neither improved nor worsened. All variables were PROMIS surveys and were T-score calculated with the mean of 50.
46
Chapter 5: Discussion
This chapter provides an interpretation of the results of the study. It discusses the
results of the study followed by sections on depression, other psychosocial factors, pain,
application episodes, and timing. This will be followed by identification of the limitations
that were encountered during the study. Lastly, the conclusion will discuss the clinical
relevance of the study and opportunities for future research.
Depression
Depression was the only variable that demonstrated a significant change,
increasing in the placebo group over the 2 weeks. The fact that participants in the 2
treatment groups, both of which used analgesic balm, did not experience increased
depression suggests that the treatments had some beneficial effect (ie, depression neither
improved nor worsened). A possible explanation is that nociception and depression share
common neurotransmitters such as norepinephrine, serotonin, and dopamine.27 When
pain is high, depression is likely to be high. Depression is thought to be 3 to 4 times more
prevalent in people with chronic pain. 28 Analgesic balms are purported to reduce pain,
and pain is linked to depression; therefore, it is likely that these participants did not
experience pain relief.
Another possible explanation for an increase in depression is a disruption in
neurotransmitter levels. Evidence suggests that a disruption in the levels of
norepinephrine, serotonin, and dopamine can also cause depression. 29 Several
antidepressant medications increase brain levels of norepinephrine, serotonin, and
dopamine.50 If medications increase these neurotransmitters, then finding another method
47
of increasing the neurotransmitters may decrease depression. Norepinephrine, serotonin,
and dopamine are released during descending pain modulation. If descending pain
modulation can be activated, it may be possible to decrease depression scores. It stands to
reason that the placebo may not have activated the descending pain modulation
mechanism, thus explaining the increase in depression.
The exact mechanisms of counterirritant-related pain reduction are not entirely
known; however, it has been suggested that analgesic balms function primarily via
placebo effect.40 People believe the analgesic balm works because they are told they will
experience a reduction in pain and experience a superficial sensation. Our study used a
placebo group in order to determine if a placebo effect could decrease pain and
psychosocial factors. In this case there was no placebo effect, because the placebo group
experienced an increase in depression scores over time.
Other Psychosocial Variables
The results revealed that there were no statistically significant changes for anger
and anxiety. The results were surprising when compared to previous research. Anger and
anxiety are common emotional responses seen after injury. 2 People may experience these
emotional responses at different times and for varying durations of time; but, overall
emotions are “complex psychophysiological states that have a quick onset, short duration,
and common cognitive antecedents.”26(p172) If anger and anxiety have a quick onset, then
decreases in those psychosocial factors would be expected after analgesic balm
application and pain reduction. That was not the case for our study because no decreases
were found over a 2-week period. Data only being collected at 2 points rather than in
48
serial collection could also provide an explanation for these results leading to the timing
of the application. This will be discussed in a later section. The type of condition, chronic
(mild or severe) or acute, could also provide an explanation of the results.
PFPS is a mild chronic condition where most people are still able to participate in
athletics and normal physical activities. The majority of participants in this study reported
their pain to be a 3 or 4 on a 10-point scale and were not diagnosed with OA. It is
possible that since PFPS pain is not severe, the anger and anxiety experienced would not
be as great as with OA or an acute injury. If anger and anxiety were not severe then
differences between baseline and 2-week levels might not show a change.
Pain
Pain is subjective and often difficult to measure. Each person interprets and
handles pain differently. For example, 2 people may have the same injury with one
person able to continue on with normal activities while the other is completely withdrawn
from daily life. An explanation of this requires an understanding of pain threshold and
pain tolerance. Pain threshold is the level of painful stimuli required to alert the person to
potential tissue damage.24 Pain threshold is the point at which pain is experienced. Pain
tolerance is the maximum amount of pain that a person can withstand. 24 Factors that
determine pain perception include age, gender, personality, past experiences, and
sociocultural factors.24 Pain tolerance increases with age in both males and females;
however, males have a higher pain tolerance than females. 51 Females are said to have a
lower pain tolerance, which conflicted with our study.
49
People dealing with chronic pain, such as AKP, often find pain relief elusive. The
participants live with pain daily and have learned to deal with it; thus, they have a higher
pain tolerance. The PROMIS surveys do not measure the severity of pain, but instead
considers how pain affects daily activities and behaviors. Since participants have a higher
pain tolerance, the results from the pain interference and pain behavior surveys might not
be accurate.
The results did not agree with prior research. White and Sage32 treated delayed
onset muscle soreness with an analgesic balm and a placebo resulting in the analgesic
balm group experiencing greater pain relief than the placebo group.32 White and Sage33
completed more research in 1971 using the same methods as the previous study except
using different conditions, osteoarthritis and rheumatoid arthritis. That study also
concluded that the analgesic balm group experienced more pain relief than the placebo
group.33 Both of these studies found a decrease in pain in both groups with the analgesic
balm group experiencing greater pain relief. Our study did not replicate these results
because a reduction in pain was not seen with any of the groups.
One Application Versus Multiple Applications
The frequency of application may provide some insight into why effects were not
seen in pain and most of the psychosocial factors. Participants were required to apply the
analgesic balm at least once a day but no more than 4 times a day per manufacturer’s
instructions. Some of the participants only applied the analgesic balm once, out of
convenience for them, while others applied the analgesic balm multiple times a day. The
analgesic balm studies performed on cats showed physiologic effects (HR and MAP),
50
related to pain, decreased 20 minutes after a single application. 34,35,36 These effects wore
off and returned to baseline levels 40 minutes to 2 hours after application. If our
participants only applied the analgesic balm once a day it is possible that the effects were
not long term and relief from pain or psychosocial factors was not experienced. The more
frequently the analgesic balm was applied, the more likely long-term effects would be
seen. The participants who applied the analgesic balm 4 times a day could have
experienced long-term effects. If the analgesic balm was applied 4 times a day then
effects may be more long term. This could be similar to taking an oral pain reliever every
4 to 6 hours to make sure it stays in the system and its effects last longer.52 The frequency
of analgesic balm application could also be a factor in the timing of analgesic balm
application.
Timing of Application
The timing of analgesic balm application could also play a large role in
experiencing relief from pain and psychosocial factors. There can be acute effects of
analgesic balms34,35,36; but their longer term effects are not as well documented. A
participant applied an analgesic balm and took the survey 2 hours later. The effects of the
analgesic balm could have worn off and the survey scores might not reflect the benefits
of the analgesic balm. This translates to the clinical aspect where an analgesic balm is
applied to an athlete to help reduce pain to allow game participation. The analgesic balm
is applied prior to warm-up and by the time the game begins, the effects may wear off. It
is very important to find the best time to apply the analgesic balm in order to produce and
maintain the effects.
51
This study only required participants to apply the analgesic balm for 2 weeks.
Extending the time beyond baseline and 2 weeks might provide better results. Nolano et
al. found that if an analgesic balm was applied for 3 weeks, then the nerves of the
application area would be desensitized, not allowing for pain to be felt.53 If the nerves
became desensitized and pain was no longer felt, it is possible that psychosocial factors
would decrease. Participants were given the option of how many times a day they could
apply the analgesic balm. They were asked to apply the cream at least once a day but no
more than 4 times a day. If participants were required to apply the analgesic balm 4 times
a day the effects might be greater and last longer.
Limitations
Previous clinical trials investigating the efficacy of analgesic balms were
inconclusive for many reasons and this study was no different. This study only used
women 18 to 40 years old. Psychosocial factors and pain are often different between men
and women, potentially affecting the results. Women tend to show more anger than men
when exercise is not done regularly. 3 Participants also had to have AKP either in the form
of PFPS or OA. This limited the participants that were available for the study. In
addition, PFPS is often difficult to diagnose because it is a nontraumatic injury with no
mechanism. It is also difficult to treat for the same reason. Analgesic balm application
will not correct the underlying cause of PFPS but could not provide pain relief to allow
exercise to return to normal. Since corrective exercises were not done to resolve the
underlying problem, it is likely pain would have increased again once analgesic balm
application was ceased.
52
The surveys used in this study to measure the psychosocial variables did not ask
questions specifically related to injuries. Instead the questions pertained more to how
these factors affected everyday life, which is another limitation. Surveys pertaining to
anger, anxiety, and depression as they relate to injuries need to be created and validated.
One of the biggest limitations of this study is that there was no way to ensure that the
participants were truthful in their responses on the surveys. The participants have
completed the surveys only because they had to fulfill the requirements for the study;
therefore, the survey results might not be entirely accurate.
Conclusion
The results of the study were not what were anticipated; however, the results did
demonstrate that analgesic balms appear to have an effect on psychosocial factors,
particularly depression. There was a significant interaction in depression scores from
baseline to 2 weeks. This difference was found amongst the placebo group. The analgesic
balm groups did appear to attenuate depression, showing promise for the effectiveness of
analgesic balms. There were no significant findings for anger, anxiety, pain interference,
and pain behavior. Based on the results of this study it appears that the dermatomal
method of applying an analgesic balm may not be better than applying the analgesic balm
over the painful area, but further research is warranted.
There are many opportunities to continue and expand this research in the future.
Research could incorporate men into the study and expand the age range of subjects.
Surveys could be developed and used that encompass more of the injury component to
the psychosocial factors. Extending the time frame could also be done with future
53
research. Adding another two weeks of application and a two week period after
application could provide further insight into analgesic balms. Different types of active
ingredient, other than menthol, could be used. Lastly, research could be done using
multiple active ingredients to determine if one ingredient works better than another.
Analgesic balms may still prove to be useful in many treatments once more research has
been done to examine the effectiveness and proper application method.
54
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40. Sawynok J. Topical and peripherally acting analgesics. Pharmacol Rev.
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increase the functional variability of TRPM channels. Naunyn Schmiedebergs
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joint. Ann Rheum Dis. 1992;51:844-849.
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randomization techniques for clinical trials. J Athl Train. 2008;43(2):215-221.
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[Column]. Primary Psychiatry. 2007;14(5):21-23. Primary Psychiatry Web site.
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pain sensation. Pain. 1999;81:135-145.
61
Appendix A: Recruitment Flyer
62
Appendix B: Informed Consent Form
Title of Research: The effects of two analgesic balm applications on physical
function, pain, and psycho-social factors related to injury.
Researchers: Leigh Spring AT, Ben Rockwell, AT, Brian Ragan PhD AT
You are being asked to participate in research. For you to be able to decide
whether you want to participate in this project, you should understand what the
project is about, as well as the possible risks and benefits in order to make an
informed decision. This process is known as informed consent. This form
describes the purpose, procedures, possible benefits, and risks. It also explains
how your personal information will be used and protected. Once you have read
this form and your questions about the study are answered, you will be asked to
sign it. This will allow your participation in this study. You should receive a
copy of this document to take with you.
Explanation of Study
You have been chosen to participate in this study because you have pain in
the front of your knee during activity. This study is being done to look at the
effects of two different ways to apply analgesic balm, a sports cream that
produces a warming sensation, on physical function, pain and feelings you may
experience related to injury such as pain, anxiety, anger, and depression.
Currently, there is little research done in this area.
If you agree to participate, you will be asked to apply the analgesic balm to
your leg multiple times over the area. This will be done as necessary but no
more than 4 times per day. You will be asked to fill out a daily application log
and complete a home exercise program at least 3 times per week. You will also
be asked to fill out online surveys every 2 weeks for a 6 week period. At the
conclusion of every 2 week period, you will be asked to return the application
diaries and containers of analgesic balm. At this time you will receive more
analgesic balm and logs for the next 2 week period.
You should not participate in this study if you have sustained a previous
injury to your knee in the past 12 months or have had a previous knee surgery
in the past 12 months. You should also not participate in this study if you have
an allergy to the active ingredient, menthol, or any of the inactive ingredients
such as allatonin, aloe barbadensis leaf juice, carbomer, diisopropyl adipate,
eucalyptus globulus leaf oil, glycerin, mentha piperita (peppermint) oil, methyl
salicylate, SD alcohol 40, steareth-2, steareth-21, thymus vulgaris (thyme) oil,
63
tocopheryl acetate, or triethanolamine. You should also not have an allergy to
any aspirin-containing products.
Your participation in the study will last for 6 weeks. Daily involvement will be
required for the application of the analgesic balm and logging of the
applications. This process should only take about 3 minutes each time the
analgesic balm is applied. The home exercise program should be completed at
least 3 times per week and will take approximately 30 minutes to complete. On
the days that the home exercise program is not completed participants will only
spend about 12minutes participating in the study, 3 minutes for each
application and a possibility of 4 applications per day. On days the home
exercise program is completed, participation will take about 42 minutes. At the
end of the week participants will expect to have spent approximately 3 hours
participating in the study. This may vary depending on how many applications
of the analgesic balm are needed. Every 2 weeks you will be asked to spend
approximately 20 minutes completing 9 different surveys. This time may vary
depending on the amount of questions you are asked to complete in each
survey.
Risks and Discomforts
Risks or discomforts that you might experience are a strong smell during
and after application of the analgesic balm. You may also experience skin
irritations in the form of a rash, discomfort from warming aspects of the
analgesic balm’s active ingredients, or decreased sensation over the application
site. You could experience pain, swelling, blistering, and burns. To minimize the
risk of those adverse effects, you should not bandage the area tightly or apply
local heat, such as a heating pad. If you should experience any of those
symptoms or have an allergic reaction to the analgesic balm, discontinue use of
the product immediately and seek medical attention.
Benefits
Individually, you may benefit by experiencing some pain relief and an
increase in function and quality of life. The findings from this study may help
improve treatment administration.
Confidentiality and Records
Your study information will be kept confidential by storing the master code
list with identifiable information will be stored in a locked filing cabinet in an
64
office with a locked door. The surveys will be located on a password-protected
computer.
Compensation
A drawing will be done involving participants within the study. For every 2
weeks you complete, your name will be entered into a raffle drawing for a
chance to win 1 of 10 $50 prizes. You can earn up to 3 chances for the $50
prize. The drawing will occur after all the data has been collected for the study.
You are unable to win the raffle drawing more than once.
Contact Information
If at any time you experience a “bad reaction” or an allergic reaction to the
analgesic balm, discontinue use immediately and seek medical attention. Make
sure you contact researchers and inform them of the signs and symptoms that
you experienced. If you are unsure if a reaction is normal, discontinue use and
contact researchers with any questions you might have regarding this issue.
If you have any questions regarding this study, please contact:
Leigh Spring (740) 704-7170 [email protected]
Ben Rockwell (715) 450-2420 [email protected]
Brian Ragan (740) 597-1876 [email protected]
OR
[email protected]
If you have any questions regarding your rights as a research participant, please
contact Jo Ellen Sherow, Director of Research Compliance, Ohio University,
(740)593-0664.
By signing below, you are agreeing that:
 you have read this consent form (or it has been read to you) and have
been given the opportunity to ask questions and have them answered
 you have been informed of potential risks and they have been
explained to your satisfaction.
 you understand Ohio University has no funds set aside for any injuries
you might receive as a result of participating in this study
 you are 18 years of age or older
 your participation in this research is completely voluntary
 you may leave the study at any time. If you decide to stop
participating in the study, there will be no penalty to you and you will
not lose any benefits to which you are otherwise entitled.
Signature
Date
65
Printed Name
[2/13/13]
Version Date:
66
Appendix C: Screening Questionnaire
Subject ID Number: _______________________
Date (Phone): ___________________
Date (In person): ___________________
Analgesic Balm Study
Over-the-phone Screening & Medical Questionnaire
Hello, my name is __________________________. Thank you for showing
an interest in my research project. I am going to read you a list of
questions to determine if you are eligible for this study. Please listen
carefully and answer to the best of your ability. If you do not understand
the question please ask. When we meet in person, I will review this
screening and then perform a physical evaluation of your knee(s) and legs.
Screening Criteria
Phone
In person
□Yes □No Are you between the ages of 18 and 40 years old? □Yes □No
How old are you? _________
□Yes □No Are you pregnant or do you have a reason to □Yes □No
believe that you may be pregnant?
□Yes □No Do you have a medical condition that may impair □Yes □No
your balance performance?
□Yes □No
Have you ever been diagnosed with osteoarthritis
(OA) in the knee?
□Yes□No
67
□Yes □No
□ Right □ Left □ Both
Have you had an injury to your muscles,
bones, or joints in the last 12 months that caused
you to be less active?
□Yes □No
If yes, what? __________________________
Exclusion Criteria
Phone
□Yes □No
In Person
□
Have you ever injured your knee, in the past
Yes
12 months, that required you to go to the
doctor?
If yes, what? _____________________________
□No
□ Right □ Left □ Both
□Yes □No
Have you ever had knee surgery?
□ Right □ Left □ Both
□Yes □No
□Yes □No Do you have any form of dermatologic condition? □Yes □No
If yes, what? ______________________________
Where? __________________________________
□Yes □No
□ □
Do you have any known allergies?
Yes
No
If yes, to what? _____________________________
_________________________________________
_________________________________________
68
Inclusion Criteria
□Yes □No
□Yes □No
Do you have pain in the front of your knee(s)?
□ Right □ Left □ Both
Has the pain in your knee(s) lasted at least
4 weeks?
Phone
□Yes □No
□Yes □No
□Yes □No
□Yes □No
In Person
Rate your pain on a scale of 0 to 10.
(0 = no pain, 10 = worst pain in your life)
Do you have pain with any of the
following activities? :
□Yes □No
□Yes □No
□ Yes □ No
Squatting
□ Yes □ No
During or after activity
□ Yes □ No
Ascending or descending stairs
□ Yes □ No
Standing after sitting for long
periods of time
Clinical Notes
What type of physical activities are you doing now? (Include mode, frequency,
duration, and average total hours per week of participation)
69
What type of physical activities were you doing prior to your knee becoming
painful? (Include mode, frequency, duration)
What is your occupation?
How long has your knee been painful? (months, years)
Did you seek any treatment for your previous knee pain? What type?
What medications are you currently taking?
Contact Information
What is the best way to get in contact with you?
Email:
Phone (cell or home):
What days and times are best?
Do you have access to a computer and the internet?
End of Phone Screening
-----------------------------------------------------------
70
Clinical Examination/Inspection
In Person
□Yes □No
Evidence or history of any meniscal or other
intra-articular pathology?
Evidence or history of any knee ligament
laxity or tenderness?
□Yes □No
Evidence or history of any patellar tendon,
iliotibal band, or pes anserine tenderness?
Evidence or history of a positive patellar
apprehension sign?
Evidence or history of Osgood-Schlatter or
Sinding-Larsen-Johanssen syndromes?
Evidence or history of effusion?
Evidence or history of hip or lumbar referred
pain?
Evidence or history of recurrent patellar
subluxation or dislocation?
Evidence or history of surgery to the knee
joint?
□Yes □No
□Yes □No
□Yes □No
□Yes □No
□Yes □No
□Yes □No
□Yes □No
71
Evidence or history of non-steroidal antiinflammatory drug or corticosteroid use
24 hours prior to testing?
□Yes □No
Clinical Examination/Inspection Cont.
Evidence or history of head injury or
vestibular disorder within the last 6
months?
Any visible dermatological conditions
over the area of application?
Any open wounds over the area of
application?
□Yes □No
□Yes □No
□Yes □No
72
Appendix D: PROMIS Anxiety Long Form
Emotional Distress - Anxiety – Calibrated Items
Please respond to each
item by marking one box
per row.
In the past 7 days...
EDANX01
EDANX02
EDANX03
EDANX05
EDANX07
EDANX08
EDANX12
EDANX13
EDANX16
I felt fearful
I felt
frightened
Never
Rarely
 
1
2
1
2
 
Sometimes
Often
Always






3
3
4
4
5
5
It scared me
when I felt
nervous
 



I felt anxious
 



 



I was
concerned
about my
mental health
 



I felt upset
 



 



I felt like I
needed help
for my
anxiety
I had a racing
or pounding
heart
I was anxious
if my normal
routine was
disturbed
1
1
1
1
2
2
2
2
1
2
1
2
 
1
2
3
3
3
3
3
3

3
4
4
4
4
4
4

4
5
5
5
5
5
5

5
73
Sometimes
Often
Always
 



I was easily
startled
 



I had trouble
paying
attention
 



I avoided
public places
or activities
 



I felt fidgety
 



 



In the past 7 days…
EDANX18
I had sudden
feelings of
panic
EDANX20
EDANX21
EDANX24
EDANX26
EDANX27
EDANX30
EDANX33
I felt
something
awful would
happen
I felt worried
Never
1
1
1
1
EDANX40
EDANX44
2
2
2
2
1
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
 



 



I worried
about other
people's
reactions to
me
 



I found it
hard to focus
on anything
other than my
anxiety
 
1
2



Never
Rarely
Sometimes
Often
Always
1
2
3
4
5
I felt terrified
In the past 7 days…
EDANX41
2
1
1
1
EDANX37
Rarely
My worries
overwhelmed
me
I had
1
2
2
2
 
 
3
3
3
3


4
4
4
4


5
5
5
5


74
EDANX46
EDANX47
EDANX48
EDANX49
EDANX51
EDANX53
EDANX54
EDANX55
twitching or
trembling
muscles
1
I felt nervous
I felt
indecisive
2
3
4
5
 



 



1
2
1
2
3
3
4
4
5
5
Many
situations
made me
worry
 



I had
difficulty
sleeping
 



I had trouble
relaxing
 



I felt uneasy
 



 



I felt tense
I had
difficulty
calming down
1
1
1
2
2
2
1
2
1
2
1
2
 
3
3
3
3
3

3
4
4
4
4
4

4
5
5
5
5
5

5
75
Appendix E: PROMIS Anger Long Form
Emotional Distress Anger – Calibrated Items
Please
respond to
each item by
marking one
box per row.
In the past 7
days...
EDANG01
EDANG03
EDANG04
EDANG05
EDANG06
EDANG07
EDANG09
EDANG10
Never
Rarely
Sometimes
Always
Often
When I was
frustrated, I
let it show
  
I was
irritated
more than
people knew
  

I felt envious
of others
  

I disagreed
with people
  

I made
myself angry
about
something
just by
thinking
about it
  

I tried to get
even when I
was angry
with
someone
  

I felt angry
  

  

When I was
mad at
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
1
2
3
1
2
3

4
4
4
4
4
4
5
5
5
5
5
5
4
5
4
5
76
someone, I
gave them
the silent
treatment
EDANG11
In the
past 7
days..
.
EDANG15
EDANG16
EDANG17
EDANG18
EDANG21
EDANG22
EDANG25
EDANG26
EDANG28



  
I felt like
breaking
things
1
2
Never
Rarely
I felt like I
was ready to
explode

When I was
angry, I
sulked
3
4
5

Often
Always
 



 


I felt resentful
when I didn't
get my way

 


I felt guilty
about my
anger

 


I felt bitter
about things

 


I felt that
people were
trying to
anger me

 


I stayed angry
for hours

 


I held grudges
towards
others

 


I felt angrier

 


1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
Sometimes



3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
77
than I thought
I should
EDANG30
I was grouchy

1
In the
past 7
days…
EDANG31
EDANG35
EDANG37
EDANG42
EDANG45
EDANG47
EDANG48
EDANG54
 
2
3

4

5
Never
Rarely
Sometimes
I was stubborn
with others



I felt annoyed



 



 
I had a bad
temper
1
1
1
2
2
2
3
3
3
Always
Often
 
4
5
4
5
4
5
I had trouble
controlling my
temper



 
I was angry
when I was
delayed



 
Even after I
expressed my
anger, I had
trouble
forgetting
about it



 
I felt like I
needed help
for my anger



 
I was angry
when
something
blocked my
plans



 
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
78
Appendix F: Depression Long Form
Emotional Distress - Depression – Calibrated Items
Please respond to each
item by marking one
box per row.
In the past 7 days...
EDDEP04
EDDEP05
EDDEP06
EDDEP07
EDDEP09
EDDEP14
EDDEP17
EDDEP19
EDDEP21
I felt
worthless
Never
Rarely
Sometimes
1
2
3
Often
Always
 
 
I felt that I
had nothing to
look forward
to
 
 
I felt helpless
 
 
 
 
I withdrew
from other
people
1
2
3
1
2
3
1
2
3
4
4
5
5
4
5
4
5
I felt that
nothing could
cheer me up
 
 
I felt that I
was not as
good as other
people
 
 
I felt sad
 
 
 
 
I felt that I
wanted to
give up on
everything
I felt that I
was to blame
for things
1
1
2
2
3
3
1
2
3
1
2
3
 
1
2
3
4
4
5
5
4
5
4
5
 
4
5
79
In the past 7 days…
EDDEP22
EDDEP23
EDDEP26
EDDEP27
EDDEP28
EDDEP29
EDDEP30
EDDEP31
EDDEP35
EDDEP36
EDDEP39
I felt like a
failure
Never
Rarely
Sometimes
Often
Always
1
2
3
4
5
 
 
I had trouble
feeling close
to people
 
 
I felt
disappointed
in myself
 
 
I felt that I
was not
needed
 
 
I felt lonely
 
 
 
 
I felt
depressed
1
1
1
2
2
2
3
3
3
1
2
3
1
2
3
4
4
4
5
5
5
4
5
4
5
I had trouble
making
decisions
 
 
I felt
discouraged
about the
future
 
 
I found that
things in my
life were
overwhelming
 
 
I felt unhappy
 
 
 
 
I felt I had no
reason for
living
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
80
In the
past 7
days…
EDDEP41
EDDEP42
EDDEP44
EDDEP45
EDDEP46
EDDEP48
EDDEP50
EDDEP54
Never
Rarely
Sometimes
Often
Always
4
5
I felt
hopeless
I felt
ignored by
people
  
  
 
I felt upset
for no
reason
  
 
I felt that
nothing
was
interesting
  
 
I felt
pessimistic
  
 
I felt that
my life was
empty
  
 
I felt guilty
  
 
  
 
I felt
emotionally
exhausted
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
1
2
3
1
2
3
 
4
4
4
4
4
5
5
5
5
5
4
5
4
5
81
Appendix G: Pain Interference Long Form
Pain Interference – Calibrated Items
Please
respond to
each item by
marking one
box per row.
In the past 7
days…
PAININ1
PAININ3
PAININ5
PAININ6
Not at all
A little
bit
How
difficult
was it for
you to take
in new
information
because of
pain?

 
 
How much
did pain
interfere
with your
enjoyment
of life?

 
 
How much
did pain
interfere
with your
ability to
participate
in leisure
activities?

 
 
How much
did pain
interfere
with your
close
personal
relationship

 
 
1
1
1
1
2
2
2
2
Somewhat
3
3
3
3
Quite a
bit
4
4
4
4
Very
much
5
5
5
5
82
s?
PAININ8
PAININ9
PAININ10
How much
did pain
interfere
with your
ability to
concentrate
?

 
 
How much
did pain
interfere
with your
day to day
activities?

 
 
How much
did pain
interfere
with your
enjoyment
of
recreational
activities?

 
2
3
 
Not at all
A little
bit
Somewhat
2
3
1
1
1
2
2
3
3
4
5
4
5
4
5
In the past
7 days…
PAININ11
PAININ12
PAININ13
How often did
you feel
emotionally tense
because of your
pain?

How much did
pain interfere
with the things
you usually do
for fun?
How much did
pain interfere
with your family
Quite a
bit
Very
much
 
 

 
 

 
 
1
1
1
2
2
3
3
4
4
4
5
5
5
83
life?
PAININ17
PAININ18
PAININ19
PAININ20
PAININ22
How much did
pain interfere
with your
relationships
with other
people?

 
 
How much did
pain interfere
with your ability
to work (include
work at home)?

 
 
How much did
pain make it
difficult to fall
asleep?

 
 
How much did
pain feel like a
burden to you?

 
 
How much did
pain interfere
with work around
the home?

 
2
3
 
4
5
Not at all
A little
bit
Somewhat
Quite a
bit
Very
much
2
3
4
5
In the past 7
days…
PAININ31
PAININ34
PAININ35
1
1
1
1
1
2
2
2
2
3
3
3
3
4
4
4
4
5
5
5
5
How much did
pain interfere
with your ability
to participate in
social activities?

How much did
pain interfere
with your
household
chores?

 
 
How much did
pain interfere
with your ability

 
 
1
1
1
 
2
2
3
3
 
4
4
5
5
84
to make trips
from home that
kept you gone for
more than 2
hours?
PAININ36
PAININ48
PAININ49
PAININ56
PAININ14
How much did
pain interfere
with your
enjoyment of
social activities?

 
 
How much did
pain interfere
with your ability
to do household
chores?

 
 
How much did
pain interfere
with your ability
to remember
things?

 
 
How irritable did
you feel because
of pain?

 
 
How much did
pain interfere
with doing your
tasks away from
home (e.g.,
getting groceries,
running errands)?

 
 
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
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