J Appl Physiol 106: 1112–1118, 2009.
First published February 5, 2009; doi:10.1152/japplphysiol.91508.2008.
The effect of microdialysis needle trauma on cutaneous vascular responses
in humans
Gary J. Hodges, Caroline Chiu, Wojciech A. Kosiba, Kun Zhao, and John M. Johnson
Department of Physiology The University of Texas Health Science Center San Antonio, Texas
Submitted 20 November 2008; accepted in final form 2 February 2009
that over the past 20 yr has
become a common procedure in humans. The first report of the
in vivo use of microdialysis in humans concerned studies of the
interstitial space (19). In the last decade or so, microdialysis
coupled with laser-Doppler flowmetry has provided a powerful
system for in-depth mechanistic analysis of how the cutaneous
circulation functions in vivo. The microdialysis technique
often involves insertion of a “guide,” typically a 25-gauge
needle, intradermally for ⬃2.5 cm before exiting. The microdialysis fiber is placed through the lumen of this needle; the
needle is then removed, leaving the fiber within the dermis
(e.g., Refs. 6, 8, 9, 16, 20, 26, 29). Used in this manner, the
microdialysis fiber allows the exchange of substances with the
interstitial space. One of the primary advantages of this technique is that substances can be applied locally without systemic
effects. Several sites on a single human forearm can thereby be
individually manipulated as desired. The combination with
laser-Doppler flowmetry offers a nearly ideal approach to
probing the mechanisms of control in the cutaneous circulation. However, it is possible that the insertion trauma caused by
the placement of the microdialysis fiber confounds efforts to
establish the mechanisms involved in the cutaneous vascular
responses examined. In some instances, ice is used as a
temporary anesthetic, which reduces or eliminates the insertion
pain. This procedure might be sufficient to lessen the triple
response of Lewis (18), that is, flare, local erythema, and
wheal, which might affect cutaneous vascular responses (2, 7).
The use of ice before needle insertion, as a temporary anesthetic, is common but it is assumed to be sufficiently benign
that the process will not affect the vascular responses. However, no work thus far has thoroughly investigated the effects
of the preparatory procedures on cutaneous vascular responses.
Local anesthesia (LA) is also effective in preventing the pain
of fiber insertion (5, 11, 15, 21). LA is not typically used with
microdialysis fiber placement unless sensory nerve blockade is
a part of the question, because the application of LA may affect
the vascular responses (5, 11, 15, 21). Wong et al. (34) recently
provided evidence for an involvement of substance P in the
cutaneous vascular response to whole body heat stress. Because sensory nerves are a known source for substance P, this
general consideration that LA might affect the response would
appear to be well founded. However, that notion has not been
directly tested.
Therefore, we designed this study to test whether 1) placement of a microdialysis fiber has an effect on cutaneous
vascular responses; 2) using ice as a temporary anesthetic
before needle insertion has an effect on subsequent cutaneous
vascular responses; 3) application of topical LA affects cutaneous vascular responses; and 4) whether, in conjunction with
microdialysis fiber insertion, either ice or LA has any such effects.
Cutaneous vascular responses were assessed as the reflex vasodilator responses to whole body heat stress. This was chosen
because the response to whole body heating is large and thus
likely to show any differences among treatments.
Address for reprint requests and other correspondence: J. M. Johnson, Dept.
of Physiology-MSC 7756, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900
(e-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
skin blood flow; active vasodilation; ice; local anesthesia; laserDoppler flowmetry
MICRODIALYSIS IS A TECHNIQUE
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8750-7587/09 $8.00 Copyright © 2009 the American Physiological Society
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Hodges GJ, Chiu C, Kosiba WA, Zhao K, Johnson JM. The
effect of microdialysis needle trauma on cutaneous vascular responses
in humans. J Appl Physiol 106: 1112–1118, 2009. First published
February 5, 2009; doi:10.1152/japplphysiol.91508.2008.—Microdialysis enables in-depth mechanistic study of the cutaneous circulation
in humans. However, whether the insertion or presence of the microdialysis fiber (MDF) affects the skin circulation or its responses is
unknown. We tested whether the cutaneous vascular response to
whole body heating (WBH) was affected by MDF or by pretreatment
with ice (part 1) or local anesthesia (LA; part 2). Eleven subjects
participated, 9 in part 1 and 8 in part 2 (5 participated in both). In both
parts, four sites on the forearm were selected, providing untreated
control, MDF only, ice or LA only, and combined MDF plus ice or
LA. A tube-lined suit controlled whole body skin temperature, which
was raised to ⬃38°C for WBH. Skin sites were instrumented with
laser-Doppler flow probes. Data were expressed as cutaneous vascular
conductance (CVC). Baseline levels were not different among sites
(P ⬎ 0.05). In part 1, the internal temperature for the onset of
vasodilation was higher (P ⬎ 0.05) with MDF with or without ice
pretreatment than at untreated control sites (control 36.6 ⫾ 0.1°C, Ice
36.5 ⫾ 0.1, MDF 36.8 ⫾ 0.1°C, and Ice⫹MDF 36.8 ⫾ 0.1°C). Peak
CVC during WBH was decreased (P ⬍ 0.05) by MDF (control 73 ⫾
7 vs. MDF 59 ⫾ 6% of maximal CVC). Ice (73 ⫾ 6% of maximal
CVC) or Ice⫹MDF (69 ⫾ 6% of maximal CVC) did not affect (P ⬎
0.05) peak CVC compared with control. In part 2, the temperature
threshold for the onset of vasodilation was increased by MDF with or
without LA treatment and by LA alone (P ⬍ 0.05; control 36.6 ⫾
0.1°C, MDF 36.7 ⫾ 0.1°C, LA 36.8 ⫾ 0.1°C, and LA⫹MDF 36.8 ⫾
0.1°C). Peak CVC was decreased by MDF (control 69 ⫾ 6% of
maximal CVC vs. MDF 58 ⫾ 8% of maximal CVC; P ⬍ 0.05). LA
only (65 ⫾ 10% of maximal CVC) or MDF in the presence of LA
(73 ⫾ 12% of maximal CVC) did not affect (P ⬎ 0.05) peak CVC
compared with control. Thus LA or MDF increases the temperature
threshold for the onset of vasodilation. MDF alone decreases the peak
vasodilator response in CVC to WBH; however, this attenuation did
not occur if ice or LA is used before MDF placement. Ice or LA alone
do not affect the peak response in CVC to WBH. How those treatments prevent or reverse the effect of MDF placement is presently
unclear.
NEEDLE TRAUMA AND SKIN BLOOD FLOW
METHODS
J Appl Physiol • VOL
the forearm used for the blood flow measurements. This arrangement
allowed independent control of local skin temperature and whole body
skin temperature. Oral temperature was recorded by a sublingual
thermocouple. The subject was encouraged to keep his or her mouth
closed, with the thermocouple as stationary as possible, and to breathe
through the nose. All variables were collected at 1-s intervals and
stored as 20-s averages for offline analysis.
Drugs. Sensory nerve blockade was achieved through the use of a
topical local anesthetic cream (2.5% lidocaine and 2.5% prilocaine,
Fougera, Melville, NY). The cream was applied to an area of 8 cm2
under an occlusive dressing where it was left for a minimum of 2 h
(11, 15). The area was tested for sensory loss both before needle
insertion and at the completion of the study.
Protocols. The protocol for part 1 is shown in Fig. 1. Four skin
sites on the ventral aspect of the forearm were randomly chosen. Two
of these sites were treated with an ice pack for 5 min. One site treated
with ice and one site not treated with ice were then instrumented with
microdialysis fibers. Hence, there was one untreated site, one site only
pretreated with ice, one with only a microdialysis fiber, and a fourth
site with both ice pretreatment and a microdialysis fiber.
In part 2, again four skin sites on the ventral aspect of the forearm
were randomly chosen. The protocol is shown in Fig. 2. Two of these
sites were treated with a topical LA for a minimum of 2 h. One site
treated with LA and one site not treated with LA were then instrumented with microdialysis fibers, yielding an untreated site, a site
pretreated with only LA, one site with a microdialysis fiber but no LA,
and a site with both.
In both parts, a 90-min period was allowed for trauma resolution
because this has developed as the “norm” (e.g., Refs. 12, 15, 21, 34)
from a study by Anderson et al. (2), who showed that skin perfusion
returns to normal following the placement of a microdialysis fiber in
about an hour, and Groth et al. (7), who found that histamine levels
return to normal levels after 30 min. The experiment began with a
10-min baseline phase. Whole body heating was then performed, with
the aim of increasing oral temperature by 0.7°C. This was achieved by
pumping 48°C water through the tube-lined suit. After 30 – 45 min,
when oral temperature had increased by 0.7°C, cool water (25°C) was
Fig. 1. Outline of the protocol for part 1. Four skin sites on the ventral aspect
of the forearm were randomly chosen. Two were pretreated with ice for 5 min;
one of these was sites was instrumented with a microdialysis probe. A skin site
not treated with ice was also instrument with a microdialysis probe. This
arrangement yielded untreated control, ice pretreatment only, microdialysis
fiber only, and both ice and microdialysis fiber. Ninety minutes were allowed
to elapse before data collection. Baseline measurements were then recorded for
10 min, and whole body heat stress was performed for 30 – 45 min, until oral
temperature was raised by 0.7°C. LW, local warming; Tskin, whole body mean
skin temperature; Tloc, local skin temperature; Temp, temperature; N/A, not
applicable.
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Subjects. The local Institutional Review Board approved this study.
All subjects were fully informed of the methods and risks before
written informed consent was obtained. All 12 subjects (9 men and 3
women; age 28 ⫾ 4 yr) who participated (9 in part 1 and 8 in part 2;
5 who participated in part 1 did so in part 2) were healthy nonsmokers, nonobese (body mass index: 24 ⫾ 1.9 kg/m2), were not taking any
medications, and refrained from alcoholic and caffeinated beverages
for at least 12 h before the study. For the female subjects, the phase
of the menstrual cycle was recorded because previous studies have
reported that the vasodilator responses to whole body heating are
affected by female reproductive hormones (4); however, in the context
of the questions in the present study, the data from the female subjects
displayed no differences from those of the male subjects, so the data
were combined.
Instrumentation. In all studies, subjects had four ventral forearm
skin sites chosen for assessment; two of these sites were prepared with
microdialysis probes, placed intradermally, and two without. As
described previously (6, 16), these custom-built microdialysis probes
consisted of 1 cm of microdialysis tubing (regenerated cellulose, inner
diameter 200 ␮m, 18-kDa nominal molecular mass cutoff) attached at
each end to polyimide tubing. For both parts, a 25-gauge needle was
introduced aseptically for ⬃2.5 cm into the dermis before exiting. The
microdialysis fiber was introduced into the skin via the lumen of the
needle. The needle was then removed, leaving the probe in place. All
probes were placed in this manner. The effects of the insertion trauma
were allowed to subside over the following 90 min (3, 8). The
different probes were placed 3–5 cm apart. In part 1, immediately
before implantation of one of the microdialysis fibers, the area of
forearm skin was temporarily anesthetized by the application of an ice
pack for 5 min; the other microdialysis fiber was inserted into the
dermis without pretreatment with ice. The ice treatment was also
performed at one of the skin sites not instrumented with a microdialysis fiber; the final site was untreated (neither fiber placement nor
ice pretreatment). In part 2, a topical local anesthetic cream was
applied for a minimum of 2 h at two skin sites. At one of those sites,
a microdialysis fiber was placed. As in part 1, a microdialysis fiber
was placed without any pretreatment and a fourth site served as an
untreated control site.
Measurements. All measurements were performed with the subjects resting in the supine posture. Skin blood flow was measured
from the ventral aspect of the forearm by laser-Doppler flowmetry
(MoorLAB, Moor Instruments, Axminster, UK), and it was expressed
as laser-Doppler blood flow (14, 22). Laser-Doppler blood flow
measures are exclusive to the skin because they are not contaminated
by blood flow to underlying skeletal muscle (24). Local temperature
control at the sites of blood flow measurement was achieved with
custom-designed metal Peltier cooling-heating probe holders (e.g.,
Refs. 1, 8, 10, 15, 35). These controlled surface temperature within
0.05°C over an area of 6.3 cm2 with the exception of a small aperture
(0.28 cm2) in the center of the holder to enable placement of the
laser-Doppler probe. A thermocouple placed between the skin surface
and the probe holder enabled local skin temperature assessment and
feedback control. In the present study, local skin temperature was
maintained at 34°C until the end of the study, at which time it was
raised to 42°C for 30 min to achieve maximal cutaneous vasodilation
(13, 27). Blood pressure was recorded noninvasively and continuously
by the Penaz method (23) from the left middle finger (Finapres,
Ohmeda, Madison, WI). Mean arterial pressure was obtained from the
electrical integration of the continuous blood pressure signal. Cutaneous vascular conductance (CVC) was calculated as the ratio of
laser-Doppler flow to mean arterial pressure (in arbitrary units).
Whole body skin temperature was the weighted mean from six
thermocouples placed on the body surface (28) and was controlled by
the use of water-perfused suits (e.g., Refs. 1, 5, 10, 28). The suit
covered the entire body surface apart from the head, hands, feet, and
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NEEDLE TRAUMA AND SKIN BLOOD FLOW
pumped through the suit to return the subject to a thermoneutral
temperature. Local skin temperature at the site of measurement was
then increased to 42°C to obtain maximal CVC values (14, 28).
Data analysis. Comparison among sites included the level of CVC
achieved at the peak of heating and the level of internal temperature
at which CVC began to increase during body heating (threshold for
vasodilation). CVC for each site is expressed as a percentage of
maximal CVC for that site (%CVCmax). Temperature thresholds at
which the onset of vasodilatation occurred during whole body heating
were chosen by an investigator who was blinded as to the source of
data. Analysis of baseline and maximal CVC values was performed
using a repeated-measures one-way ANOVA. Statistical significance
was assumed when P ⬍ 0.05. Power analysis indicated that with a
variance in means of 10 and a common standard deviation of 5
%CVCmax, for both parts 1 and 2, a minimum of seven subjects would
be required for a P ⬍ 0.05 with 95% power (nQuery Advisor v.3);
with nine subjects in part 1 and 8 in part 2, the power for each part
was 99.
Fig. 3. Summary of the data from all 9 subjects in part 1 for baseline
measurements in cutaneous vascular conductance (CVC). Application of ice,
insertion of a microdialysis fiber, or the combination of the pair did not affect
baseline blood flow. CVC is expressed as a percentage of maximal CVC
(%max).
Fig. 5). However, neither ice pretreatment (73 ⫾ 6% CVCmax)
nor fiber placement with ice pretreatment (69 ⫾ 6% CVCmax)
significantly affected (P ⬎ 0.05) the response in CVC to
subsequent whole body heating compared with that at the
control site (Fig. 5). These findings are the same if the changes
in CVC from baseline to peak heating are used.
Part 2. Baseline CVC values were statistically (P ⬎ 0.05)
unaffected by the application of topical LA, insertion of a
microdialysis fiber, or the combination of the two compared
with that at the untreated control site (Fig. 6), although there
was a trend for a slight decrease (P ⫽ 0.07) at both of the sites
treated with LA compared with the appropriate untreated site
(control 17 ⫾ 4, LA 14 ⫾ 2, Fiber 15 ⫾ 3, and LA⫹Fiber
12 ⫾ 2% CVCmax).
As found in part 1, the temperature threshold at which the
onset of cutaneous vasodilation occurs during whole body
heating was increased by the placement of the microdialysis
fiber. Fiber placement with or without LA treatment, or LA
RESULTS
Part 1. Baseline CVC values, expressed as %CVCmax, were
statistically (P ⬎ 0.05) unaffected by the prior application of
ice, insertion of a microdialysis fiber, or their combination
compared with that at the untreated control site (Fig. 3).
With body heating, the internal temperature thresholds for
the onset of vasodilation at the sites with fibers placed with or
without ice pretreatment were significantly (P ⬍ 0.05) higher
than at the untreated control site (control 36.6 ⫾ 0.1°C vs.
Fiber 36.8 ⫾ 0.1°C and Ice⫹Fiber 36.8 ⫾ 0.1°C; Fig. 4). The
onset of cutaneous vasodilation at the Ice⫹Fiber was also
significantly (P ⬍ 0.05) higher than the ice only site (36.8 ⫾
0.1°C vs. 36.5 ⫾ 0.1°C; Fig. 4). Pretreatment with ice had no
statistically significant effect on vasodilator threshold, either
with or without fiber placement (P ⬎ 0.05; Fig. 4).
The peak response in CVC during whole body heating was
significantly (P ⬍ 0.05) decreased by fiber placement on its
own (control 73 ⫾ 7% CVCmax vs. fiber 59 ⫾ 6% CVCmax;
J Appl Physiol • VOL
Fig. 4. Influence of ice, microdialysis fiber placement, and the combination on
the temperature threshold for the onset of vasodilatation during whole body
heat stress during part 1. Values are for 9 subjects. Fiber insertion, with or
without ice pretreatment, significantly increased the temperature threshold at
which vasodilatation occurred. *P ⬍ 0.05 relative to control and ice-treated
skin sites.
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Fig. 2. Outline of the protocol for part 2. Four skin sites on the ventral aspect
of the forearm were randomly chosen. Two were pretreated with local
anesthesia (LA) for 2 h; one of these sites was instrumented with a microdialysis probe. A skin site not treated with LA was also instrument with a
microdialysis probe This yielded an untreated control, LA treated only,
microdialysis fiber only, and both LA and microdialysis fiber. Thereafter, the
protocol was the same as for part 1. Skin at both LA-treated sites was tested
for sensory loss at the beginning and end of the study.
NEEDLE TRAUMA AND SKIN BLOOD FLOW
treatment alone, caused temperature thresholds to be significantly (P ⬍ 0.05) higher than at the untreated control site
(control 36.6 ⫾ 0.1°C, fiber 36.7 ⫾ 0.1°C, LA 36.8 ⫾ 0.1°C,
and LA⫹Fiber 36.8 ⫾ 0.1°C; Fig. 7). Nevertheless, there was
no significant difference (P ⬎ 0.05) in the onset of vasodilation
at the LA⫹Fiber site compared with that of the LA only site
(Fig. 7). Similarly, there was no statistical difference between
thresholds at the Fiber and LA⫹Fiber sites (P ⬎ 0.05; Fig. 7).
As in part 1, the peak response in CVC to whole body
heating was significantly (P ⬍ 0.05) decreased by fiber placement (control 69 ⫾ 6% CVCmax vs. fiber 58 ⫾ 8% CVCmax;
Fig. 8). LA only (65 ⫾ 10% CVCmax) or fiber placement in the
presence of LA (73 ⫾ 12% CVCmax) did not significantly
affect (P ⬎ 0.05) the peak response in CVC to whole body
heating compared with that at the control site (Fig. 8). These
results are the same if the changes in CVC from baseline to
peak heating are analyzed.
Fig. 6. Baseline CVC from part 2. Values are for 8 subjects. Application of
topical local anesthesia, insertion of a microdialysis fiber, or the combination
of the pair did not affect baseline blood flow. CVC is expressed as a percentage
of maximal CVC.
J Appl Physiol • VOL
Fig. 7. Internal temperature thresholds for the onset of vasodilation in part 2.
Values are for 8 subjects. All treatments raised the temperature threshold
compared with the untreated control. There were no statistical differences
among the three treatments. *P ⬍ 0.05 that LA, Fiber and LA⫹Fiber sites are
significantly different compared with the control site.
DISCUSSION
The major findings of this investigation are that microdialysis fiber placement offsets the temperature threshold for the
onset of cutaneous vasodilation during heat stress to a higher
temperature and that this occurs with or without the anesthetic
effects of ice pretreatment or the application of topical LA
before fiber placement. Also, LA alone (but not ice pretreatment alone) increases the temperature threshold for the onset of
active vasodilation. Fiber placement alone decreased the ultimate vasodilator response in CVC to whole body heating;
however, this attenuation did not occur if ice or LA is used
before fiber placement. Ice and LA alone did not affect the
ultimate response in CVC to whole body heating.
As expected from earlier studies (2, 7), resting CVC was
unaffected in all instances; there were no statistically identifiable differences in the baseline levels of blood flow among the
four treatments in either part 1 or part 2. This outcome is
Fig. 8. Peak CVC during body heating from all 8 subjects for part 2. Oral
temperature was raised 0.7°C. Insertion of a microdialysis fiber significantly
reduced the response in CVC to the whole body heating. However, placement
of a fiber following treatment with topical local anesthesia restored the
complete response; local anesthesia alone had no significant effect. *P ⬍ 0.05
is significant different compared with the control and the LA⫹Fiber sites.
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Fig. 5. Mean data from all 9 subjects for the response in CVC to the whole
body heating stress in part 1. Oral temperature was raised 0.7°C. Insertion of
a microdialysis fiber significantly reduced the response in CVC to the whole
body heating. However, placement of a fiber immediately following the
application if ice restored the complete response; ice alone had no effect *P ⬍
0.05 compared with the control and ice-treated sites.
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NEEDLE TRAUMA AND SKIN BLOOD FLOW
J Appl Physiol • VOL
properties reduce the inflammatory response, in which case
histamine might not be depleted.
The lack of effect of LA on neurogenic vasodilator function,
although surprising, is in keeping with our laboratory’s earlier
observations of intact vasoconstrictor function following such
LA treatment (11, 15). Our laboratory’s earlier speculation was
that a greater depth of autonomic than sensory fibers may
account for this observation. Deeper application of the anesthetic, for example by microdialysis, would be an interesting
test of this possibility.
The combination of LA and needle insertion was consistently associated with an unchanged peak vasodilator response
to whole body heat stress (in comparison to responses at the
untreated control site). Interestingly, application of LA alone
did not reduce the ultimate vasodilator response to whole body
heat stress. Cracowski et al. (5) recently showed that 40 min
application of LA cream significantly reduced perceived needle
insertion pain and after 2 h did not affect postocclusive or
thermal hyperemia. Here, having applied topical LA for 2 h,
there was a complete absence of any sensation to the needle
insertion. This loss of sensory function was maintained
throughout the investigation. The presence of the sensory
blockade from LA throughout the study (unlike that from ice)
suggests this not to be a generally useful adjunct to microdialysis. However, it produced a potentially important finding.
Wong et al. (34) showed that desensitization of neurokinin type
1 (NK1) receptors decreased the response in CVC to whole
body heating. This was an intriguing and provocative finding,
suggesting that substance P is involved in the active vasodilator
system. However, the evidence was gained in an unconventional manner. Rather than antagonism of NK1 receptors, they
were desensitized by pretreating the skin with an infusion of
substance P via microdialysis, exploiting a finding from their
previous work (33). Although sensory nerves are a major
source of substance P in the skin, our finding that treatment
with topical LA did not affect the peak response to whole body
heating at the LA only site suggests that substance P of sensory
nerve origin is not involved in the cutaneous vasodilator
response to whole body heating.
A thorough examination of the effect of the trauma of the
insertion of the microdialysis fiber on the cutaneous vascular
responses had not previously been performed. This study
highlights the importance of ensuring that all sites within a
study are treated in a similar manner. That simple procedures
such as the application of an ice pack to temporarily anesthetize the skin before needle insertion are valuable, not only to
reduce subject discomfort, but the findings of this investigation
would suggest that is useful in preventing effects that can cause
small, albeit statistically significant changes in the cutaneous
vascular responses to stimuli.
Experimental considerations. During the 0.7°C increase in
oral temperature not all skin sites reached a plateau; this might
be a potential source of error in the interpretation that peak
CVC values are different between treatments. That is, the
lower peak response may relate to the delay in the onset of
vasodilation, and, if greater thermal stress or a longer period of
body heating were used to allow stabilization of flow, the
present findings might not be observed. It is also important to
note that the use of oral temperature as a guide to the degree of
heat stress has some potential sources of error; although breathing only through the nose is encouraged, breathing through the
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consistent with previous work, in which the initial increase in
histamine levels from the trauma due to the microdialysis
needle insertion subsides in about 30 min (7). Our laboratory
(e.g., Refs. 12, 15, 25) and others (e.g., Refs. 17, 30, 31, 33)
routinely wait 1–2 h following the placement of microdialysis
fibers before taking measurements, and baseline blood flows
that are not perceptibly different from skin that has not had
such treatment are observed. As for the efforts to eliminate
pain from fiber insertion, ice was originally used because we
believed that its effects would be relatively benign and temporary while still decreasing or eliminating the pain of needle
insertion (6). Indeed, we found that such pretreatment with ice
had no measurable effects on either the vasodilator threshold or
the degree of vasodilation with subsequent body heating.
Although one might expect LA to reduce baseline and/or peak
CVC due to its known vasoconstrictor effects (3), only a
statistically insignificant trend for a decline in baseline CVC at
the LA⫹Fiber site in part 2 was seen (Fig. 6) with no apparent
effect on peak CVC (Fig. 8).
The onset of vasodilation at the sites with fibers placed was
offset to higher temperatures compared with control sites. A
possible explanation for this observation is that the needle
insertion may damage a few nerve endings, thereby reducing
the ability of those areas of skin to respond to the whole body
heat stress. LA also increased the temperature at which the
onset of vasodilation occurred, possibly due to LA causing
reduced nerve function and leading to decreased sensitivity to
activation of the vasodilator system during whole body heat
stress. Previous studies of cutaneous vascular responses to
local cooling (11, 15) and local heating (21) found the initiation of the local vasoconstrictor and vasodilator responses to be
altered following treatment with LA. The finding that the
combination of ice or LA with fiber placement reverses the
increased threshold is not in keeping with this speculation
about damage to nerve fibers by fiber placement. The finding
that fiber placement increases the threshold for activation of the
active vasodilator system to a higher temperature might also be
due to fiber placement disrupting local transmitters, such as
substance P (34) or others (4, 17, 20, 25, 32, 33). It could also
be that the elevated levels of histamine observed in the first 30
min following fiber placement (7) lead to its depletion. This
scenario could affect the sensitivity of the active vasodilator
system because histamine has been suggested to be involved in
the active vasodilator response (32). Although the cause for the
displacement of threshold is not made clear by these studies,
the data are important in the use of vasodilator thresholds as an
analytic tool (e.g., Ref. 4). It is important that control sites
should have microdialysis probes if the test sites do.
Application of ice before fiber insertion partially restored the
peak vasodilator response, such that there was not a statistical
difference in peak CVC between the untreated control and ice
plus fiber sites. This could be due to the ice acting as a
temporary anesthetic and reducing an acute inflammatory response. As previously mentioned, Groth et al. (7) found that
the trauma from microdialysis fiber insertion was associated
with elevated levels of histamine. The concentration of histamine would steadily decrease and plateau about 30 min after
fiber placement. We waited 1.5 h following microdialysis fiber
placement and did not see any effects on baseline. With ice or
LA pretreatment before fiber placement, a full CVC response
to whole body heating is observed. Perhaps the anesthetic
NEEDLE TRAUMA AND SKIN BLOOD FLOW
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
ACKNOWLEDGMENTS
We thank the subjects for their participation.
Present address of G. J. Hodges: School of Kinesiology, The University of
Western Ontario, London, Ontario, Canada N6A 5B8 ([email protected]).
21.
22.
GRANTS
23.
This study was supported by National Heart, Lung, and Blood Institute
Grant R01 HL-059166.
24.
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mouth can cause large changes in temperature values, as can
changes in position of the probe in the mouth. This should not
be a problem in interpretation in the present study because data
from sites treated differently were taken simultaneously and,
therefore, at the same central temperature. There is a potential
issue reporting the changes in CVC as percentages of maximal
CVC achieved by local heating, because it is not known
whether microdialysis fiber placement affects the maximal
cutaneous vasodilator response. This would be most likely to
reduce maximal CVC through a physical effect on the microcirculation. Although such an effect is not supported by the
lack of a significant effect on baseline CVC, nevertheless the
possibility underscores the necessity of treating control and
experimental sites equally, including the placement of microdialysis fibers. Finally, these results apply to reflex responses to
body heating, but they do not necessarily anticipate the effects
of ice pretreatment, local anesthesia, or microdialysis fiber
insertion on other (e.g., vasoconstrictor) reflex responses or on
the effects of local skin warming or cooling. This would
ultimately be interesting considering the involvement of autonomic and sensory nerves and of local factors in those responses (1, 8 –12, 15, 16, 20, 21, 25, 26, 30, 35).
In summary, we found that microdialysis fiber placement
raises the temperature threshold for the onset of cutaneous
vasodilation during heat stress. This shift occurs with or
without the anesthetic affects of ice treatment or application of
topical LA before fiber placement. Furthermore, LA alone
increases the temperature threshold for the onset of active
vasodilation. Fiber placement alone decreases the peak cutaneous vasodilator response to whole body heating. Interestingly, this attenuation did not occur if ice or LA was used
before fiber placement. Ice and LA alone do not affect the peak
cutaneous vascular responses to whole body heating.
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