i20 Thursday 04 May 2006, 14:30–16:30
BSR Concurrent Orals
Concurrent Oral 7 – Chronic Pain:
Mechanisms and Management
OP53. eNOS, iNOS AND NITROTYROSINE IN COMPLEX REGIONAL
PAIN SYNDROME TYPE I
R. Gorodkin1, M. Jeziorska2, A. Freemont2 and A. Herrick1,3
1
University of Manchester Rheumatic Diseases Centre, Hope Hospital,
2
Department of Osteoarticular Pathology, University of Manchester and
3
Arthritis Research Campaign Epidemiology Unit, University of Manchester,
Manchester, United Kingdom
Background: Complex regional pain syndrome type I (CRPS) is a painful disorder
of the peripheries in which vasomotor changes play a major role. A number of laser
Doppler studies have demonstrated abnormal microvascular blood flow in the
affected limb. Endothelial and inducible nitric oxide synthase (eNOS and iNOS) are
both key enzymes regulating vasodilation, but iNOS can also be associated with
the production of free radicals. Our hypothesis was that we would find evidence of
abnormal levels of eNOS and iNOS and an increase in nitrotyrosine, (a measure of
iNOS related free radical damage), supporting a role for free radicals in the
pathophysiology of CRPS.
Methods: Nineteen patients with CRPS (mean age 46, range 25–77; 4M 15F; 9
upper limb, 10 lower limb CRPS) and 29 healthy controls (mean age 40, range 21–
59; 4M 25F; 15 upper limb and 14 lower limb) had a 4mm punch biopsy of skin
taken from either mid forearm or mid calf. Immunohistochemical staining was
carried out using eNOS, iNOS (both Serotec) and nitrotyrosine (Zymed
laboratories) monoclonal antibodies and avidin-biotin amplification. Staining of
endothelial cells and pericytes were assessed on an arbitrary scale of 0–10 (eNOS
and iNOS) where 0 ¼ no staining and 10 ¼ maximal staining. Nitrotyrosine (which
was stained differently) was assessed using a single 0–3 scale. The Mann–
Whitney U-test was used for statistical analysis.
Results: All the biopsies were carried out uneventfully. No CRPS patients reported
any worsening of their symptoms. eNOS: There were no significant differences in
endothelial and pericyte staining between the CRPS and control groups (P ¼ 0.672
and 0.820 respectively). iNOS: There was a significant difference between
endothelial staining in the CRPS biopsies compared to control biopsies
(P ¼ 0.002), but no difference in pericyte staining (P ¼ 0.972). Nitrotyrosine: No
significant differences were found between the two groups (P ¼ 0.381).
in random order. Participants are asked to record the number of times their
perception changes. They are also asked to describe what, if anything, they see
and feel, and whether they notice any change in their pain.
Results: Of 9 CRPS sufferers, 3 reported the worsening of a regionally located
pain on viewing the images. One participant reported an increase of 3 points on an
11 point numerical rating scale. Other symptoms, such as nausea, disorientation
and sweating, were also described. The symptoms abated shortly after the stimuli
were removed from sight. No healthy control (n ¼ 38) reported any somatic
sensations.
Conclusions: It is possible to worsen the pain suffered in CRPS, and to produce
other somatic sensations, by means of a visual stimulus alone. This is a newly
described finding. The reversals in perception experienced in viewing the Necker
Cube are due not only to the stimulus itself, but also to cerebral processes of
perception. Therefore it is possible that this finding will help elucidate the central
mechanisms involved in CRPS [1, 2]. However the precise nature of the visual
stimulus necessary, and the relationship of this phenomenon to the syndrome
require further investigation.
FIG. 1.
Disclosure: This study has been supported by funding from the Gwen Bush
Foundation.
References
1. McCabe et al. Rheumatology 2003;42:97–101.
2. McCabe et al. Rheumatology 2005;44:509–6.
Immunohistochemical staining data
CRPS
Healthy control
eNOS endothelial
staining
eNOS pericyte
staining
iNOS endothelial
staining
iNOS pericyte
staining
Nitrotyrosine
staining
2.20 (1.90–2.97)
1.83 (1.11–2.59)
4.00 (3.75–4.50)
3.57 (3.09–4.53)
3.80 (3.04–3.95)
4.00 (3.78–5.03)
6.50 (5.75–7.00)
6.00 (5.69–6.76)
1.50 (1.00–2.00)
1.50 (1.00–2.50)
All data show median (interquartile range).
Conclusions: To our knowledge this is the largest published cohort of skin
biopsies taken from subjects with CRPS. iNOS levels in CRPS appear to be lower
than in healthy controls with no difference in nitrotyrosine or eNOS levels. These
are unexpected findings and do not support our hypothesis of free radical mediated
damage in CRPS. However, free radical damage can occur via other routes and
the heterogeneity of CRPS makes this a difficult area to study. The safe biopsying
of these patients in this study will make further studies in this field easier to
accomplish.
OP54.
PAIN FELT IN CRPS CAN BE INCREASED BY VISUAL STIMULUS
S. J. Harrison1, J. Hall2, C. S. McCabe2,3, J. S. Lewis2,
H. Cohen2, N. D. Harris2,3,4 and D. R. Blake2,3,4
1
Faculty of Medicine and Dentistry, University of Bristol, Bristol, United Kingdom,
2
Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom, 3School
for Health, University of Bath, Bath, United Kingdom and 4Department of
Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
Background: Visual disturbance, visuo-spatial difficulties, and exacerbations of
their pain associated with these, have been reported by some Complex Regional
Pain Syndrome (CRPS) sufferers. Visually induced pain is one of a number of
anecdotal accounts of perturbations of vision and spatial awareness uncovered by
our group. We know of no published accounts of,or investigations into, this
phenomenon. We investigated the hypothesis that some visual stimuli (i.e. those
which produce ambiguous, multistable, perceptions) can induce pain and other
somatic sensations in people with CRPS.
Methods: A standardised sequence of three images, printed on A4 sized card, is
shown: a Duck/Rabbit, a Necker Cube and a rectangle. The Necker Cube is a well
known visual illusion (Fig. 1). The 2-dimensional image can be perceived as a
representation of a 3-dimensional cube in two mutually exclusive ways (as if from
above, or as if from below). These rival perceptions change suddenly and
unpredictably – the cube ‘flips’. The Duck/Rabbit is, like the Necker Cube, a
reversible, or multistable, image. The Duck/Rabbit is shown first, and is used to
illustrate the experimental task. The Necker Cube and the rectangle are shown
OP55. HYPOTHALAMIC PITUITARY ADRENAL STRESS AXIS
DYSFUNCTION INFLUENCES THE RISK OF NEW ONSET CHRONIC
WIDESPREAD BODY PAIN
J. McBeth1, A. J. Silman1, A. Gupta1, Y. H. Chiu1, D. Ray1,
R. Morriss2, C. Dickens1, Y. King1 and G. Macfarlane3
1
ARC Epidemiology Unit, University of Manchester, Manchester, United
Kingdom, 2Department of Psychiatry, University of Liverpool, Liverpool,
United Kingdom and 3Epidmeiology Group, University of Aberdeen,
Aberdeen, United Kingdom
Background: Although psychosocial factors are robust predictors of the onset of
CWP, not all ‘at risk’ subjects will develop symptoms. It is likely these individual risk
factors are mediated through one or more biological pathways. We hypothesised
that the HPA stress response system would be an important modifier of risk of new
CWP.
Methods: In the first population based prospective study to address this question
11 000 subjects were mailed a questionnaire to screen for subjects free of CWP but
psychologically at risk of future CWP based on a Somatic Symptom Checklist
(SSC) score >2 and an Illness Behaviour Scale (IBS) score >5. Of the 768 eligible
subjects identified, 349 were randomly selected for a detailed assessment of their
HPA axis function. Diurnal function was measured by morning (9 a.m.) and evening
(10 p.m.) salivary cortisol. Serum cortisol levels were measured after a low dose
(0.25 mg) overnight dexamethosone suppression test, and a tender point
examination. All subjects were followed up 15 months later to identify those with
new onset CWP. For analysis cortisol values were categorised into tertiles based
upon the distribution of values with the highest or lowest tertile (depending on HPA
parameter) being classified as the referent category. Results are presented as
odds ratios with 95% confidence intervals (CI).
Results: 245 (70%) subjects participated in the HPA assessment of whom 231
(94%) had complete follow up. Of these 26 (11.3%) reported new onset CWP.
CWP prevalence increased with age but no gender differences were evident. High
post dexamethasone OR ¼ 3.2, 95% CI (1.03, 10.1), low morning saliva [1.6 (0.6,
4.7)] and high evening saliva [1.6 (0.5, 4.9)] levels were all associated with new
CWP. In a multivariable model age, post dexamethasone serum and evening
saliva cortisol levels were independent predictors of CWP onset. Subjects
‘exposed’ to all three of these HPA parameters were almost 9 times more likely
to develop CWP [8.5 (1.5, 47.9)] when compared to those exposed to none of
these factors.
Conclusions: Among a group of psychologically at risk subjects, altered HPA axis
function strongly influences the risk of developing new CWP. This study has
BSR Concurrent Orals
Thursday 04 May 2006, 14:30–16:30
demonstrated that both disturbed physiological as well as psychological factors
may be of aetiological importance.
i21
A
OP56. CONTRALATERAL INFLAMMATORY RESPONSES DURING
ACUTE LOCALISED INFLAMMATION OF RAT HINDPAW SKIN
E. M. Roberts1, N. G. Shenker1,2, P. I. Mapp3, C. R. Stevens1 and D. R. Blake1,2
1
School for Health, University of Bath, Bath, United Kingdom, 2Royal National
Hospital for Rheumatic Diseases, Bath, United Kingdom and 3Academic
Department of Rheumatology, University of Nottingham, Nottingham,
United Kingdom
Background: Many chronic inflammatory diseases (e.g. rheumatoid arthritis) are
symmetrical. It is hypothesised that an acute, localised inflammation stimulates a
topographically precise contralateral inflammatory response, and that this is a
protective measure against further stimuli. A pro-inflammatory phenotype, altered
regulation or amplification of such processes may explain this symmetry.
Methods: Unilateral inflammation was induced in rat hindpaw skin by intraplantar
injection (100 l) of 1% carrageenan (CAR) or 1% latex spheres (LS). Forepaws
and naive rats were used as controls. To investigate a systemic response serum
IL-6 content was determined by ELISA.
Hindpaw volume (ml) was measured using plethysmometry before and after
injection (CAR at 1 and 6 h (both n ¼ 5), LS at 6 (n ¼ 6) and 24 hours (n ¼ 12)).
Rats were killed and skin dissected from all paws.
Myeloperoxidase (MPO) activity, the ability to catalyse the oxidation of
tetramethyl benzidine by H2O2 (absorbance/tissue weight (A/g)), was determined.
Sections immunostained for E-selectin and CD31 (endothelial cells) using
immunofluorescence (IF), were analysed using computer-assisted image analysis
to quantify the area of E-selectin-IF corrected for CD31-IF (%E-selectin). For the
LS-induced foreign body-mediated model cellular infiltration was determined by
counting nuclei, nerve growth factor (NGF)-IF was assessed as well as E-selectin
and NGF mRNA content by RT-PCR.
Comparisons between left and right paws and IL-6 levels were made with ttests, other data were compared with one-way ANOVAs and appropriate post
tests; *P < 0.05, **P < 0.01, ***P < 0.001, data are mean±S.D.
Results: Serum IL-6 content did not alter following injection ruling out systemic
inflammation.
During CAR-induced inflammation %E-selectin and MPO activity increased at
6 h compared to controls both ipsilaterally (CAR %E-selectin 15.1±7.2*; CAR A/
g ¼ 16.0±4.1***, naive right A/g ¼ 0.32±0.1, left A/g ¼ 0.31±0.1) and contralaterally
(CAR %E-selectin 11.3±4.6*; CAR A/g ¼ 0.69±0.2**). CAR injection did not alter
%E-selectin or MPO activity in either forepaw.
LS injection increased ipsilateral and contralateral paw volume over time
(ipsilateral, baseline 1.41±0.07, 6 h 1.75±0.09***, 24 h 1.80±0.11***; contralateral,
baseline 1.46±0.09, 6 h 1.52±0.07*, 24 h 1.55±0.07***). Cellularity increased
ipsilaterally and contralaterally at 24 h (both**). Neither E-selectin nor NGF-IF
increased in any paw; but E-selectin and NGF mRNA were upregulated in
contralateral hindpaws 6 h after LS injection (n ¼ 3). Upregulation did not occur in
naive skin, nor in forepaw skin.
Conclusions: These results support the hypothesis and provide evidence of
topographically precise contralateral inflammatory responses during unilateral
inflammation. Such ‘mirror-image’ responses may explain the symmetry of RA.
Further investigation is required to fully characterise these responses, and to
establish their role in the development of symmetrical inflammation.
Young Investigator Award Winner
B
pain in pre-adolescent school children in Lahti, Finland.
RISK FACTORS FOR DEVELOPMENT OF MUSCULOSKELETAL
PAIN IN PREADOLESCENTS: A PROSPECTIVE 1-YEAR FOLLOW-UP
STUDY
1
Results: At 1-year follow-up, 21.5% of the initially pain-free children reported newonset pain in at least one musculoskeletal area. Of them 19.4% reported nontraumatic pain and 4.0% reported traumatic pain. The neck was the most common
site for non-traumatic pain, while the lower limb was the most common site for
traumatic pain. Hypermobility was not a risk factor for either pain conditions. The
independent risk factors for non-traumatic musculoskeletal pain were headache
(OR ¼ 1.68, [95% CI 1.16–2.44]) and day tiredness (OR ¼ 1.53, [95% CI 1.03–
2.26]). The risk factors for traumatic musculoskeletal pain were vigorous exercise
(OR ¼ 3.40 [95% CI 1.39–8.31]) and day tiredness (OR ¼ 2.97 [95% CI 1.41–
6.26]), with a synergistic interaction between these two factors (P < 0.001).
FIG. 2. Incidence proportions of traumatic and non-traumatic musculoskeletal (MS)
OP57.
1,2
FIG. 1. Flow chart of the study.
3
4
A. El-Metwally , G. Macfarlane , J. J. Salminen , A. Auvinen , H. Kautiainen
and M. Mikkelsson2
1
Epidemiology Group, Department of Public Health, University of Aberdeen,
Aberdeen, Scotland, United Kingdom, 2The Rheumatism Foundation Hospital,
Heinola, Finland, 3Turku University Hospital, Turku, Finland and 4Tampere
School of Public Health, University of Tampere, Tampere, Finland
2
Background: Musculoskeletal pain is common in childhood, although not
frequently presenting to medical services. Previous studies have reported that
children with trauma-induced musculoskeletal injuries experience more physical
limitations compared to children with non-traumatic musculoskeletal pain. We
hypothesized that, with respect to underlying etiology, there exists two distinct
types of pain episodes in children: traumatic and non-traumatic pain. The aims of
this study are to determine the incidence of these two pain conditions in
preadolescents and separately investigate risk factors for their development.
Methods: A baseline survey of 1756 schoolchildren (aged 10–12 yrs) was
conducted using a structured pain questionnaire and Beighton hypermobility test.
The pain questionnaire contained a pain drawing, and the children were asked to
mark the musculoskeletal area(s) with weekly or daily pain. Pains initiated by a direct
trauma was marked with a different colour. The questionnaire also evaluated
frequency of exercise and several psychosomatic symptoms. Those who reported
no musculoskeletal pain at baseline were re-evaluated with the same pain
questionnaire at 1-year follow-up.
Conclusions: Non-traumatic pain onset was predicted by the prior report of
somatic symptoms while traumatic pain was predicted by both mechanical factors
and prior somatic symptoms. This research highlights that there may be 2 types of
pain syndrome with both distinct and common aspects of aetiology. Future
research, important for management, should determine whether they also have
distinctive prognoses.
OP58. PATIENT TREATMENT PREFERENCE INFLUENCES OUTCOME OF
LOW BACK PAIN: A RANDOMISED CONTROLLED TRIAL OF A
COMMUNITY-BASED PROGRAMME OF EXERCISE, EDUCATION AND
COGNITIVE BEHAVIOURAL THERAPY
G. T. Jones1,2, R. E. Johnson2, N. J. Wiles3, C. Chaddock4,
R. G. Potter4, C. Roberts2, D. P. M. Symmons2 and
G. J. Macfarlane1,2
1
Epidemiology Group, Department of Public Health, University of Aberdeen,
Aberdeen, United Kingdom, 2Division of Epidemiology and Health Sciences, The
University of Manchester, Manchester, United Kingdom, 3Academic Unit of
Psychiatry, Department of Community Based Medicine, University of Bristol,
Bristol, United Kingdom and 4Eastern Cheshire Chronic Pain Management
Service, Eastern Cheshire Primary Care Trust, Macclesfield, United Kingdom
Background: Each year 7% of the adult population consult their GP with low back
pain (LBP) and recent evidence suggests that half of patients will still experience
i22 Thursday 04 May 2006, 14:30–16:30
pain and disability 3 months later. LBP is multifactorial in aetiology, including both
physical and psychosocial elements. We hypothesised that a treatment programme for persons with sub-acute LBP based on exercise and education,
incorporating the principles of cognitive behavioural therapy, would result in a
reduction in pain and disability over 1 yr, compared to usual GP care supplemented
with educational material. In addition we hypothesised that the effect would be
modified by patient preference for type of treatment.
Methods: Patients, aged 18–65 yrs, in East Cheshire, consulting their GP with
LBP between Jan ’02 and July ’03 were recruited into the study. After 3 months,
those reporting pain of 20 mm on a 100 mm visual analogue scale (VAS) and
disability of 5 on the Roland and Morris Disability Questionnaire (RMDQ) were
identified and randomised to either:
– Intervention Group: a 6 week community-based programme of exercise and
education, delivered using a cognitive behavioural therapy approach; or – Control
Group: usual GP care with additional written and audio educational material.
Outcome: Pain (100 mm VAS) and disability (RMDQ), assessed at 0, 6 and 12months post-intervention.
Analysis: The effect of the intervention was evaluated using analysis of covariance,
adjusting for baseline pain and disability, age, sex, LBP history and psychological
distress. The trial had 90% power to detect a clinically significant difference of
12 mm on the VAS and 3 units in the RMDQ.
Results: Of 2068 patients invited to participate, 1152 agreed and subsequently
completed a 3-month post-consultation questionnaire, of whom 448 patients (39%)
reported disabling LBP. 280 undertook a pre-trial assessment and 234 were
randomised, 116 to the intervention. In both groups follow-up was high: >84%.
Both groups experienced a reduction in pain and disability over the 1 yr follow-up.
Compared to the control group, those who received the intervention experienced a
small and non-significant additional benefit in term of reduced pain (3.6 mm;
95%CI: 8.5 to 1.2) and disability (0.6; 1.6 to 0.4).
Prior to randomisation 114 patients (49%) stated a preference for the intervention
and 20 (8%) the control. The remainder were indifferent. There was a significant
interaction between patient preference and treatment effect. Patients who
expressed a preference for the intervention, and received it, experienced a
clinically important reduction in pain (11.7 mm; 26.2 to 2.7). However, those
who had a preference for the control, but who received the intervention, had a poor
outcome (þ15.0 mm; 13.6 to 43.5). The same was found for disability.
Conclusions: Our results add to accumulating evidence that current interventions
for LBP produce, at best, only a moderate additional benefit over usual care. In
seeking to optimise efficacy, one possible area for future study is patient
preference.
OP59. EFFECTIVENESS AND COST-EFFECTIVENESS OF THREE TYPES
OF ACTIVE PHYSIOTHERAPY USED TO REDUCE CHRONIC LOW-BACK
PAIN DISABILITY: A PRAGMATIC RANDOMISED TRIAL WITH
ECONOMIC EVALUATION
D. J. Critchley1, J. Ratcliffe2, M. V. Hurley1, S. Noonan3 and R. H. Jones4
1
Academic Department of Physiotherapy, King’s College London, London,
United Kingdom, 2School of Health and Related Research, Sheffield University,
Sheffield, United Kingdom, 3Physiotherapy Department, Guy’s and
St Thomas’ Hospitals, London, United Kingdom and 4School of Medicine,
King’s College London, London, United Kingdom
Background: Disability and healthcare costs of chronic low back pain (cLBP) are
extremely high in industrialised countries. International guidelines recommend
active physical therapy in cLBP management but there is little information about
the relative effectiveness or cost-effectiveness of different forms of active
physiotherapy.
Methods: We carried out a pragmatic, randomised, assessor-blind trial comparing
individual physiotherapy, spinal stabilisation classes and functional restoration
classes as delivered in two inner-London hospitals. Participants with non-specific
cLBP and able to participate in exercise classes were assessed at baseline and 6,
12 and 18 months (primary endpoint). Outcomes measured included activity
limitation (Roland disability questionnaire, primary outcome), pain, health-related
quality of life (EQ-5D) and work participation. NHS use and costs were measured
over 2 yr from 6 months prior to randomisation. Analysis on an intention-to-treat
basis used ANCOVA with baseline as covariant to compare the treatments.
Results: 71 participants were randomised to individual physiotherapy, 72 to spinal
stabilisation and 69 to functional restoration. 160(75%) provided follow-up data at
18/12. At baseline, participants were 64% female, 58% in social housing, 20% not
working due to back pain, mean (S.D.) age 45 (12) years, duration of problem 7.4
(9.2) years.
At 18/12, mean (CI) Roland disability score improved from 11.1 (9.6–12.6) to 6.9
(5.3–8.4) with individual physiotherapy; 12.8 (11.4–14.2) to 6.8 (4.9–8.6) with
spinal stabilisation; and 11.5 (9.8–13.1) to 6.5 (4.5–8.6) with functional restoration
(P < 0.001). There were similar significant improvements in pain, quality of life and
days off-work. Results at 6/12 and 12/12 were similar to those at 18/12. Differences
between treatments were not significant for any clinical outcomes.
Mean (S.D.) NHS costs and QALY gain over 18 months post-randomisation were
£474 (840) and 0.99 (0.27) for individual physiotherapy; £379 (1040) and 0.90
(0.37) for spinal stabilisation; and £165 (202) and 1.00 (0.28) for functional
restoration. Functional restoration physiotherapy dominated cost-utility analysis.
NHS costs for all participants for 6 months prior to baseline were £169.29 (349.71),
and were significantly lower for each six month period of the trial: 0–6
months ¼ £70.49 (452.74) (P < 0.001); 6–12 months ¼ £92.14 (502.11)
(P ¼ 0.003), and 12–18 months ¼ £103.03 (535.90) (P ¼ 0.036).
BSR Concurrent Orals
Conclusions: All three types of physiotherapy were effective at reducing disability,
pain, work absenteeism and NHS costs and improving quality of life in people with
chronic low-back pain. There were no differences in clinical effectiveness between
the different types of physiotherapy. Functional restoration physiotherapy was
associated with least health service consumption and costs and was most costeffective. These results have implications for clinicians and policy-makers seeking
to choose the most-cost effective treatments for cLBP.
OP60. LUMBAR EPIDURAL STEROIDS ARE NOT COST EFFECTIVE
IN SCIATICA (WEST STUDY)
C. Price1, N. Arden2 and L. Coglan3
1
Pain Clinic, Southampton University Hospitals NHS Trust, Southampton,
Hampshire, United Kingdom, 2MRC Rheumatology Unit, Southampton University
Hospitals NHS Trust, Southampton, Hampshire, United Kingdom and
3
Department of Economics, University of Portsmouth, Portsmouth,
Hampshire, United Kingdom
Background: Lumbar Epidural Steroids Injections (ESI’s) have previously been
shown to provide some degree of pain relief in sciatica. Number Needed To Treat
(NNT) to achieve 50% pain relief has been estimated at 7 from the results of
randomised controlled trials. Pain relief is temporary. They remain one of the most
commonly provided procedures in the UK. It is unknown whether this pain relief
represents good value for money.
Methods: 228 patients were randomised into a multi-centre Double Blind
Randomised Controlled Trial. Subjects received up to 3 ESI’s or intra-spinous
saline depending on response and fall off with the first injection. All other
treatments were permitted. All received a review of analgesia, education and
physical therapy. Quality of life was assessed using the SF36 at 6 points and
compared using independent sample t-tests. Follow up was up to 1 yr. Missing data
was imputed using last observation carried forward (LOCF). QALY’s (Quality of
Life Years) were derived from preference based heath values (summary health
utility score). SF-6D health state classification was derived from SF-36 raw score
data. Standard gambles (SG) were calculated using Model 10. SG scores were
calculated on trial results. LOCF was not used for this. Instead average SG were
derived for a subset of patients with observations for all visits up to week 12.
Incremental QALY’s were derived as the difference in the area between the SG
curve for the active group and placebo group.
Results: SF36 domains showed a significant improvement in pain at week 3 but
this was not sustained (mean 54 Active vs 61 Placebo P < 0.05). Other domains
did not show any significant gains compared with placebo. For derivation of SG the
number in the sample in each period differed. In week 12, average SG scores for
active and placebo converged. In other words, the health gain for the active group
as measured by SG was achieved by the placebo group by week 12. The
incremental QALY gained for a patient under the trial protocol compared with the
standard care package was 0.0059350. This is equivalent to an additional 2.2 days
of full health. The cost per QALY gained to the provider from a patient management
strategy administering one epidural as suggested by results was £25 745.68. This
result was derived assuming that the gain in QALY data calculated for patients
under the trial protocol would approximate that under a patient management
strategy based on the trial results (one ESI). This is above the threshold suggested
by some as a cost effective treatment.
Conclusions: The transient benefit in pain relief afforded by ESI’s does not appear
to be cost-effective. Further work is needed to develop more cost-effective
conservative treatments for sciatica.
Concurrent Oral 8 – Bone and Cartilage:
Biology and Disease
OP61. BiP: A NEGATIVE REGULATOR OF BONE REMODELLING
TARGETING THE OSTEOCLAST
V. M. Corrigall1, N. McGowan2, S. Maghji3, B. Henderson3,
A. E. Grigoriadis2 and G. S. Panayi1
1
Department of Rheumatology, KCL School of Medicine at Guy’s Hospital,
London, United Kingdom, 2Department of Craniofacial Development, KCL School
of Dentistry at Guy’s Hospital, London, United Kingdom and 3Division of Microbial
Diseases, Eastman Dental Institute, UCL, London, United Kingdom
Background: Dysregulated bone remodelling is the major cause of the pathology
of a number of human diseases, including rheumatoid arthritis. In such conditions
there is an increased presence of bone resorbing osteoclasts. To combat these
diseases, inhibitors of osteoclast differentiation are required. Our previous work
with BiP suggests that this stress protein affects the differentiation of peripheral
blood monocytes so we investigated the effect of BiP on osteoclast differentiation
from monocytes and on resorption of bone explants.
Methods: Human peripheral blood monocytes were differentiated in vitro with
macrophage-colony stimulating factor (M-CSF) and soluble receptor activator of
NF-B ligand (RANKL) in the presence or absence of BiP. Osteoclast development
was measured by the presence of F-actin rings and bone resorption by pit