To study the effect of oral gabapentin used as preemptive analgesia to attenuate post operative pain in patients undergoing abdominal surgery under general anesthesia.2O in O2 and Vecuronium 0.02 mg/kg. All cases were given Fentanyl 2µg/kg as pre medication and a repeat dose 1µg/kg at the end of the first hour. Assessment of post-operative pain was made with the visual analog score (VAS) at extubation (0 h), 2, 4, 6, 12, and 24 h post-operatively. Post-operative analgesia was provided with intravenous Tramadol. The first dose was given in the Post Anesthesia Care Unit as 2mg/kg, and repeated at 8 and 16 h. Rescue analgesia was given with Diclofenac 1.5mg/kg, slow intravenous. The number of doses of rescue analgesia in both the groups was noted.In a randomized double blind study, 60 patients were divided into two groups. Group A received 600mg gabapentin and group B oral received placebo 1 h prior to surgery. Anesthesia was induced with Propofol 2 mg/kg and Vecuronium 0.1mg/kg and maintained with 60% Nvs. 2.4 (P=0.002), 2.3 vs. 3.0 (P=0.000), 3.2 vs. 3.7 (P=0.006), 2.9 vs. 4.4 (P=0.000), 3.6 vs. 4.6 (P=0.000), and 3.7 vs.4.6 (P=0.000), respectively. Numbers of patients requiring rescue analgesia with Diclofenac were 3 vs. 14 (P=0.004).The VAS scores at 0, 2, 4, 6, 12, and 24 h were 1.9 A single oral dose of gabapentin given pre-operatively enhanced the analgesic effect of Tramadol as it also reduced the requirement of rescue analgesia with Diclofenac. Post-operative pain is not purely nociceptive in nature and may consist of inflammatory, neurogenic, and visceral components. Therefore, multimodal analgesic techniques utilizing a number of drugs acting on different analgesic mechanisms are becoming increasingly popular. Post-opeGabapentin, a structural analog of gamma aminobutyric acid, is used as an anticonvulsant drug since 1993. In addition, it has been effective in neuropathic pain, diabeticTo study the effect of oral gabapentin 600 mg given 1 h prior to surgery as preemptive analgesia to attenuate post-operative pain in patients undergoing abdominal surgery under GA.After obtaining the approval of the Institutional Ethics Committee  and written informed consent from the patients, 60 patients were included.Patients belonging to American Society of Anesthesiologists physical status I and IIPatients undergoing elective surgery under general anesthesiaAnticipated duration of surgery less than 4 hAge group between 18 and 65 yearsWeight range up to 20% of the ideal body weight for either sexHemodynamic ally stablePatients with a history of hypertension, diabetes, and liver diseasePatients with acute or chronic renal diseasePatients with known neurological diseaseNeurosurgical and cardiovascular surgical casesPregnant patientsPatients with known psychiatric disordersPatients with anticipated difficult airwayPatients on antihypertensive drugs, sedatives, hypnotics, antidepressants, and drugs with effects on the nervous systemPatients already taking oral gabapentinPatients allergic to opioids and TramadolPatients were randomly divided into two groups, with 30 patients in each group. They were randomly allocated according to computer-generated randomization. Patients in the control group received oral placebo capsules and those in the gabapentin group received 600 mg gabapentin  1 h before surgery. The study drugs were prepared by the pharmacy and an appropriate code number was assigned.2) were monitored. For pre-medication, midazolam 0.07 mg/kg, glycopyrolate 0.004 mg/kg, and fentanyl 2µg/kg were administered intravenously on the table. After adequate pre-oxygenation for 3 min, anesthesia was induced with propofol 2 mg/kg and vecuronium 0.1 mg/kg and maintained with 60% N2O in O2 on Bain’s circuit and vecuronium 0.02 mg/kg. At the end of surgery, neuromuscular block was antagonized with neostigmine 0.05 mg/kg and glycopyrolate 0.008 mg/kg. Surgeries lasting for more than 1 h were given a repeat dose of fentanyl 1µg/kg at the end of the first hour of induction. Any increase in the HR and MAP when not settling down by deepening the plain of anesthesia was given fentanyl 0.05 µg/kg subsequently. Total duration of the surgery in both the groups and the intra-operative fentanyl in both the groups were studied.In the operating room, a crystalloid infusion was started through an IV cannula. Blood pressure (MAP), heart rate (HR), and peripheral oxygen saturation , where 0 cm - “no pain” and 10 cm - “worst pain imaginable.” The VAS scores are taken immediately on extubation (0 h) and at 2, 4 6, 12, and 24 hours post-operatively.2 measured by pulse oximetry <95%, or a serious adverse event related to opioid administration.Post-operative analgesia was provided with Tramadol intravenously. The first dose was given in the PACU as 2 mg/kg and repeated at 8 and 16 h. If the patient still complained of pain, then rescue analgesia was given with diclofenac 75 mg slow intravenous over 10 min. The number of doses of rescue analgesia in both the groups were studied and compared. The occurrence of any side-effects, such as nausea and vomiting, respiratory depression, dizziness, somnolence, headache, and pruritus was recorded. Tramadol dose was omitted if the patient had a respiratory rate <12 breaths/min, an SpOAs seen in Tables As seen from Tables As seen from Tables As seen from Table The results of our pre-operative oral single-dose study investigating the acute post-operative analgesic effects of gabapentin in patients undergoing abdominal surgeries requiring general anesthesia show that gabapentin decreased post-operative pain scores at 0, 2, 4, 6, 12, and 24 h of surgery and decreased requirement of rescue analgesia when compared with placebo.e.g., centrally and peripherally acting analgesics). We used Tramadol as a fixed-dose regimen for postoperative pain control and Diclofenac as rescue analgesia to be given only when the patient demanded for it. Tramadol is widely used for moderate-to-severe post-operative pain. Its efficacy is a result of two complementary mechanisms of action: stimulation of µ-opioid receptors and inhibition of norepinephrine and 5-hydroxytryptamine reuptake in pain pathways.[Post-operative pain is not purely nociceptive in nature and may consist of inflammatory, neurogenic, and visceral components. Therefore, multimodal analgesic techniques utilizing a number of drugs acting on different analgesic mechanisms are becoming increasingly popular. The mainpathways.Non-steroidal anti-inflammatory drugs are commonly used analgesics for minor surgery and are useful adjunctive analgesics in patients undergoing major surgery, decreasing pain and opioid requirements. They are well established, effective, and inexpensive. However, their use may be limited by adverse renal, gastrointestinal, and hemostatic effects.Antihyperalgesic drugs such as gabapentin may have a role in post-operative pain, and the combination with other antinociceptive drugs may produce synergistic analgesia effects.10vs. 2.4, P=0.002) in the gabapentin group may suggest the synergistic effect of gabapentin with fentanyl. Decreased rescue analgesic requirement in the gabapentin group also suggests the synergistic effect of gabapentin with Tramadol.Significantly low VAS scores immediately after extubation, i.e. 0 h (1.9 et al, in 2004, also found that 1,200 mg gabapentin given 1 h prior to surgery significantly reduced the post-operative pain scores and Tramadol requirements in Total abdominal hysterectomy patients.Turan In animal models of nociception, gabapentin reduces the hypersensitivity associated with nerve injury, inflammation, and pain after surgery.9 Mechani9Gabapentin significantly decreased morphine consumption and pain in patients after mastectomy althoughGabapentin is well tolerated. It has few side-effects and minor interactions with other drugs when used for the treatment of chronic pain. We did nPreemptive use of gabapentin significantly decreases the post-operative pain and rescue analgesic requirement in patients undergoing abdominal surgery under general anesthesia.


Because previous studies have suggested that motorized non-surgical spinal decompression can reduce chronic low back pain (LBP) due to disc degeneration (discogenic low back pain) and disc herniation, it has accordingly been hypothesized that the reduction of pressure on affected discs will facilitate their regeneration. The goal of this study was to determine if changes in LBP, as measured on a verbal rating scale, before and after a 6-week treatment period with non-surgical spinal decompression, correlate with changes in lumbar disc height, as measured on computed tomography (CT) scans.A retrospective cohort study of adults with chronic LBP attributed to disc herniation and/or discogenic LBP who underwent a 6-week treatment protocol of motorized non-surgical spinal decompression via the DRX9000 with CT scans before and after treatment. The main outcomes were changes in pain as measured on a verbal rating scale from 0 to 10 during a flexion-extension range of motion evaluation and changes in disc height as measured on CT scans. Paired t-test or linear regression was used as appropriate with p < 0.05 considered to be statistically significant.2, 21 females and 9 males, and an average duration of LBP of 12.5 weeks. During treatment, low back pain decreased from 6.2 (SD 2.2) to 1.6  and disc height increased from 7.5 (1.7) mm to 8.8 (1.7) mm (p < 0.001). Increase in disc height and reduction in pain were significantly correlated .We identified 30 patients with lumbar disc herniation with an average age of 65 years, body mass index of 29 kg/mNon-surgical spinal decompression was associated with a reduction in pain and an increase in disc height. The correlation of these variables suggests that pain reduction may be mediated, at least in part, through a restoration of disc height. A randomized controlled trial is needed to confirm these promising results.NCT00828880 An estimated 80% of the population will suffer from low back pain (LBP) at some point of their lives. Low bacWhile the management of persistent low back pain remains hotly debated, the traditional approach has been non-surgical treatment with analgesia supplemented by physiotherapy. Given the limited efficacy of these modalities, there are also a number of alternative interventions such as massage, spinal manipulation, exercises, acupuncture, back school and cognitive behavioral therapy. The twoThe goal of this study was therefore to determine if changes in LBP, as measured on a verbal rating scale, before and after a 6-week treatment period with motorized non-surgical spinal decompression, correlate with changes in lumbar disc height, as measured on computed tomography scans.This is a retrospective cohort study of patients who underwent a 6-week treatment protocol of non-surgical spinal decompression via the DRX9000. A HIPAA  waiver was obtained through Quorum IRB. This waiver permitted a review of medical records and access to CT scans ordered as part of standard of care.Clinical Trial Registration Number: NCT00828880Patients and their medical records were eligible for inclusion if the patient was at least 18 years of age, consented for the 6-week treatment protocol, and presented with chronic LBP of at least 3 out of 10 on a verbal rating scale and was due to either discogenic LBP or disc herniation according to a radiological diagnosis using standard medical definitions. Discogenic LBP is most succinctly defined as a loss of lower back function with pain due to disc degeneration. Degenerative disc diseases often emerge when abnormal stresses cause the nucleus gelatinosus to unevenly distribute weight, the annular fibrosis and end plate incur structural damage, and a destructive inflammatory response is triggered to accelerate and perpetuate the degeneration of the disc. A herniated disc (synonymous with a protruding or bulging disc) arises when the intervertebral disc degenerates and is weakened to such an extent that cartilage is pushed into the space containing the spinal cord or a nerve root and causes pain[All patients were treated at the Upper Valley Interventional Radiology facility . Patient symptoms were evaluated by medical history review, physical examination, and a current CT scan (not older than 2 months prior to the start of treatment) to support a diagnosis of chronic discogenic LBP due to bulging, protruding or herniated intervertebral discs that may have been brought on by degenerative disc disease. Patients were only included if pre- and post-treatment CT scans were performed on the same device, measurements taken by the same investigator (WM), and data recorded on standard collection forms. One height measurement was taken by WM for each of the intervertebral discs under study per CT scan. Accuracy of data was confirmed by a second investigator (JP), but only one measurement was made of each intervertebral disc per CT scan. All CT scans analyzed were performed at least one hour after the subject got out of bed. The first CT scan was performed within two months before the initiation of the treatment, and the second CT scan at least one day after or on the day immediately before the final treatment session.Exclusion criteria for enrollment in the study were any patients with metastatic cancer; previous spinal fusion or placement of stabilization hardware, instrumentation or artificial discs; neurologic motor deficits; bladder or sexual dysfunction; alcohol or drug abuse; or litigation for a health-related claim . Limitations of the spinal decompression system also led to the exclusion of patients with extremes of height (< 147 cm or > 203 cm) and body weight (> 136 kg).Patients received treatment with the DRX9000  as dictated by the intervention's operating guidelines. In shorInitial decompression force was adjusted to patient tolerance, starting at 4.54 kg (10 lbs) less than half their body weight. If a patient described the decompression pull as "strong or painful," this distraction force was decreased by 10%-25%. In subsequent treatment sessions, the distraction force was increased as tolerated to final levels of 4.54 kg to 9.07 kg (10 to 20 lbs) more than half their body weight. Patients continued to use analgesics prescribed by their physicians before enrollment, but were allowed to use additional non-steroidal pain medication should their pain increase temporarily and permitted to discontinue pain medication as needed. During the routine physical examination performed by WM prior to beginning the non-surgical spinal decompression treatment session, at the first and final visits maximal pain was evaluated during a flexion-extension range of motion exam with the question "How strong is your pain on a scale of 0-10 with 0 being no pain and 10 as bad as it could be?"The first main outcome for this study was the change in pain during a range of motion evaluation measured on an 11-point verbal rating scale (VRS), with 0 being no pain and 10 being pain as excruciating as could be imagined, before and after the 6-week spinal decompression treatment regimen.The second main outcome was the change in average disc height as measured by CT scan. For each patient, average disc height of L3-L4, L4-L5 and L5-S1 was calculated before the first treatment session and at least one day after or on the day before the last treatment session.We assumed data to be normally distributed unless exploratory analyses suggested otherwise, in which case a Kolmogorov-Smirnov test was to be applied. Since the treatment effect was defined as the difference between before and after the therapeutic intervention, a paired t-test was applied to test whether there was a reduction in pain and an increase in disc height. For the main hypothesis, the correlation between disc height changes and low back pain, we applied linear regression to quantify the relationship with Pearson's correlation coefficient to determine statistical significance.Sample size estimations were performed to have sufficient power to test with a two sided type I error of 0.05 and type II error of 0.2 (80% power). Given the sizeable treatment effect reported in the retrospective chart review and also in the prospective pilot study mentioned in the introduction, we expected a reduction in range of motion pain from 6 to 2, with a standard deviation of 2.5. This resulted in a sample size estimation of only 5 patients. To test changes in disc height, we expected a standard disc height of about 8 mm with diseased discs being slightly more compressed, i.e. at about 7.5 mm, and anticipated discs after the decompression treatment to measure at about 8.25 mm. Assuming a standard deviation of 1.0 mm, we estimated a required sample size of 16 patients in order to show a difference. The sample size for the main hypothesis, that the degree of pain reduction is associated with the amount of increase in disc height, was more difficult to estimate since no previous study had determined a correlation coefficient. Therefore, we chose a coefficient of 0.5 for a conservative expectation, resulting in a required sample size of 26 patients. Taking into consideration the possibility of drop-outs, we aimed to collect data from 30 patients.2, and an average duration of LBP of 12.5 (± 19) weeks with a score of 6.3 (± 2.2) on the VRS  age of 65 (± 15) years, a body mass index of 29 (± 5) kg/mThe maximum force during the first treatment was on average 33.9 (± 6.8) kg and gradually increased during subsequent treatment visits to 52.4 (± 7.6) kg (Table Low back pain decreased from 6.2 (± 2.2) to 1.6  and disc height increased from 7.5 (± 1.7) to 8.8 (± 1.7) mm (p < 0.001) , with a 1 mm increase in disc height being associated with a reduction of 1.86 on the 11-point verbal rating scale  we did not find a correlation between age and treatment success. With regards to the elderly cohort of patients analyzed in this retrospective study, it is possible that a younger patient population might respond differently to the non-surgical spinal decompression treatment given that they would generally have less disc degeneration, be more active, and have less co-morbidity than the elderly population studied here. Yet this is a hypothesis that remains to be tested in a future prospective study investigating therapies to alleviate LBP in younger patients. While we largely believe the range of muscle tone during non-surgical spinal decompression to be the main reason for different treatment effects, other reasons for variability could be differing stages and degrees of degenerative disc disease, an assortment of activity levels, and a wide spectrum of concomitant treatments ranging from chiropractic interventions and pain medication cocktails.2 = .13, while statistically significant, there is room for an argument suggesting that perhaps the placebo effect played a role in the positive outcome. Both limitations of the current retrospective study indicate the need for a randomized placebo-controlled trial to establish a more concrete relationship between the anatomical disc changes attributed to the non-surgical spinal decompression intervention and the reduction of LBP.One limitation of this study is the lack of a control group. This is especially relevant for herniated discs, because of the significant rate of spontaneous recovery,19. A coPatients with chronic discogenic low back pain are usually on a wide range of analgesics, and pain and analgesic consumption is generally positively correlated. As a result, interventions that reduce pain typically lead to a reduced consumption of analgesics and thus counteract the treatment effect of the intervention (suppressor effect). The fact that a significant reduction of pain was observed even though analgesics were not controlled for corroborates the observation of pain relief through non-surgical spinal decompression.Finally, the follow-up period was too short to comment on the permanency of pain relief. However, this was not within the scope of this study and the duration of the effect is not essential to substantiate our primary finding that restoration of disc height through non-surgical spinal decompression is associated with decreased discogenic low-back pain. The next step will be to obtain long-term results, e.g. 1 or 2 years after the last treatment cycle, to a) investigate whether treatment effects are long lasting and to b) more importantly, establish whether there is a long term correlation between disc height increase and pain reduction.In this study of non-surgical spinal decompression for chronic discogenic low back pain we were able to demonstrate an association between the restoration of disc height and pain relief. The correlation of these variables suggests that pain reduction may be mediated, at least in part, through a restoration of disc height. These results call for a randomized placebo-controlled trial to substantiate the efficacy and elucidate the mechanism of this promising treatment modality.The authors themselves declare that they have no competing interests.NEMA Research is a Clinical Research Organization that is involved in evidence-based research development and was the lead sponsor implementing the protocol for this clinical trial on behalf of Axiom-Worldwide.CA contributed to the statistical analysis and drafting the manuscript, OSC contributed to the statistical analysis of the data, WM is responsible for the assessments made, data collection, and data review, CR performed statistical analysis and assisted with writing the manuscript, AM assisted with drafting the manuscript, EG contributed to drafting, editing, and formatting the manuscript, MS contributed to drafting and editing the manuscript, JVP performed the data review. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/155/prepub


Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year) of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system.Index Group), and advice to stay active and on how to cope with pain, provided by a physician (Control Group). Pain intensity, disability and health status were measured by questionnaires.Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409), recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (95% CI: 10-30) and disability  at 26-week, as well as at 52-week follow-ups . The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005). There were also significant differences in improvement in bodily pain and social function  favoring the Index Group.89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD) = 21%, Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck pain.Current Controlled Trials ISRCTN56954776. Back and neck pain are very common, have multiple etiologies, and often recurs -4, and aOne common non-invasive treatment is manual therapy, which is provided by several groups of health care providers such as naprapaths, physiotherapists, chiropractors and osteopaths. Manual therapy involves a variety of procedures directed at the neuromusculoskeletal structures.The most well studied manual techniques for back and neck pain is spinal manipulation/mobilization and massage therapy, respectively. There is sufficient evidence from systematic reviews that spinal manipulation therapy (SMT) is an effective treatment for back pain -9. BronfRegarding massage therapy, the evidence from systematic reviews is strong that it is an effective treatment for low back pain ,13. It hThere are also systematic reviews that include studies that in a pragmatic way have evaluated the effect of a combination of manual therapies. A review from 2008 concluded regarding neck pain without radicular symptoms, that manual therapy and exercise interventions are effective, but that none of the studied treatments are superior to any other in the short or long term .In naprapathic manual therapy a combination of manual techniques  are used to increase physical function and decrease pain in the neuromusculoskeletal system. We have found few studies that have been set up to study the effect of such a pragmatic combination of several manual techniques on back and neck pain, and they have conflicting results -19.Naprapathy is a health profession characterized by focusing on shortened or pathologic soft and connective tissues around the spine and other joints. Naprapathy is common in Sweden, Norway and Finland, and is also practiced in the USA where it was first initiated in 1907. Naprapaths have a five years full-time education, are part of the Swedish health and medical care system, and licensed from the National Board of Health and Welfare in Sweden. We have performed a pragmatic RCT with the aim of comparing the effect of naprapathic manual therapy  to the effect of evidence-based advice on staying active provided by a physician for non-specific back and/or neck pain. The intention was not to evaluate the different components in the treatments separately, but to compare the treatments, standardized as far as possible, the way they usually are carried out in outpatient clinics. The publication on the short-term effects showed significant differences between the groups regarding pain intensity, disability and perceived recovery, at 7- and 12-week follow-ups favoring naprapathy . The aimThis pragmatic randomized controlled trial, called "the Swedish BJORN-trial", was carried out in compliance with the Helsinki Declaration, and was approved by the Ethics Committee of the Karolinska Institutet (Diary No. 03-657).subjective opinion based on the estimated pain and disability in the questionnaires filled in before the examination, and the results of the anamnesis and physical examination), evidence-based advice during the past month, surgery in the painful area, acute disc herniation, spondylolisthesis, stenosis or "red flags" [Participants were recruited by advertising mainly among employees  at two public companies in Stockholm, Sweden from March to September 2005. Potential participants were asked to contact the study administration if they fulfilled the inclusion criteria (pain now and the previous two weeks or longer in back and/or neck of the kind that brought about marked dysfunction at work and/or in leisure time). The study administrator made the first-step exclusions . Subjects fulfilling the participation criteria were scheduled for an appointment at the study center where they gave their informed consent and answered an extensive self-administered questionnaire. Next an experienced physician (one of four) performed a medical examination, made a diagnosis, and prescribed medication if necessary. Further exclusions were made based on the following exclusion criteria: too mild symptoms , indicating the two interventions. Subjects were sequentially numbered in the order they came to the study center and received the assignment envelope with the corresponding number. The physician performed the unmasking after the assessments and the medical examination, so that the assistant, the physician and the patient were all blind to the group assignment until after all subjects' baseline data were collected.The treatments in both groups were conformed to the patients' condition, but standardized as far as possible by several group meetings held in advance. The naprapaths were told only to use techniques they had learned at the education center. The content in the evidence-based advice and support were carefully discussed in group with the physicians in order to make the care reliable.For patients in the Index Group, one of eight participating experienced licensed naprapaths was contacted for a first appointment within a week. A maximum of six treatments were given within six weeks in the naprapaths private clinic, and a combination of naprapathic manual techniques  was given adapted to the patients' condition. Preventive and rehabilitating advice on for the patient applicable physical activity and ergonomics were often given. Each appointment lasted for about 45 minutes, and precise notes were kept about the treatment, the progress, and any adverse reactions.Evidence-based care is in this study defined as support and advice on staying active and on pain coping strategies, according to guidelines and evidence-based reviews ,21,22. TAll outcomes were self-rated by web-based (61%) or postal questionnaires five times during the year following the inclusion. The primary outcomes pain and disability were measured by the Chronic Pain Questionnaire (CPQ) with three items on pain and three on disability with a numerical 11-point scale -26. In tFour dichotomized outcomes were defined in advance based on what is believed to correspond to a clinically significant improvement -33:improvement in pain: at least a two-step decrease (compared to baseline) in pain score (CPQ).1) improvement in disability I: at least a one-step decrease (compared to baseline) in disability score (CPQ).2) improvement in disability II: at least a one-step decrease (compared to baseline) in disability score (WDQ).3) totally recovered: a pain score less or equal to 1 and a disability score equal to 0 (CPQ).4) Secondary outcome was health status measured with The Medical Outcomes Study Short Form-36 Health Survey (SF-36) after 26 and 52 weeks ,35. The Power calculation based on the dichotomization of CPQ described above, determined the sample size to 400 patients and indicated a power of >80% to detect a relative risk of 1.2-1.3 for a clinically important improvement in pain or in disability.All analyses were performed using an "intention to treat" principle . To estiGeneralized Estimating Equations (GEE) were performed to analyze the effect on pain and disability (dichotomized) over the total follow-up time . The final model for improvement in pain and disability respectively, included the following terms in addition to the treatment variable: location of pain (back or neck), follow-up occasion and an interaction term between location of pain and follow-up occasions. The GEE method extends standard regression analysis, taking into account the covariance between repeated measurements of pain and disability ,41.In the analyses of the outcomes "improvement in pain" and "improvement in disability", patients with scores at baseline less than required to attain these improvements were excluded. In analyses of neck and back pain patients respectively, patients with concurrent pain in the neck and back (n = 25) were treated both as neck pain patients and back pain patients.Crude SF-36 data were transformed and standardized using recommended procedures and to receive the dichotomization regarding good health, values from a Swedish population was used ,35.All analyses were performed by a statistician who was not involved in the project, using SAS statistical software version 9.1.3. An assistant not involved in the project handled all data registration.Among the 522 subjects that contacted the trial administration, 431 were eligible and 409 were randomly assigned to one of the two treatments. The assigned had a mean age of 47 years, were mainly women (71%), and were mainly suffering from neck pain (58%). For many, duration of pain was more than a year (56%). Analyses of the treatments actually given in the Index Group showed that 98% received massage, 83% stretching, 57% spinal mobilization and 81% received spinal manipulation at the second consultation. Eighty-nine percent completed the 26- week follow-up and 85% the 52-week follow-up. The flow of participants through each stage of the trial and details about dropouts are shown in Figure Baseline demographics and clinical characteristics of the groups are shown in Table Figure A higher proportion in the Index Group had a clinically important improvement in pain intensity , disability on CPQ  and disability on WDQ  at 26 weeks, as well as at 52 weeks   were better in the Index Group at 26 weeks and at 52 weeks follow-ups, but the differences were only statistically significant regarding the dimensions bodily pain and social function Table .Additional analysis on back and neck pain patients separately are presented in Table This pragmatic RCT was performed with the aim of investigating if naprapathic manual therapy is effective for non-specific back and/or neck pain. The control treatment was support and advice to stay active and on pain coping strategies ,21,22. WSeparate subgroup analysis of back and neck pain patients showed similar results, but indicated that the naprapathic manual treatment might be more effective for neck pain patients. A limitation in this discussion is that the back pain subgroup is small and the statistical power low.The non-specific effects of the hands-on approach and the potentially intensive patient-therapist interaction in the Index Group due to more treatment sessions have probably contributed to the results. We do not believe that this difference in attention is the only reason to the results. Specific effects from the manual therapy on the function in the neuromusculoskeletal system probably also contributed. This assumption is made based on the documented effect of two of the manual techniques in naprapathic manual therapy, spinal manipulation/mobilization and massage, respectively ,12,13,42No study is published that has evaluated the long-term effect of naprapathic manual therapy, which precludes comparing the results to earlier findings. Some trials have evaluated the long-term effect of other manual therapy strategies where several manual techniques as spinal manipulation/mobilization and soft tissue techniques as massage are combined, as is the case in naprapathic manual therapy. The UK BEAM pragmatic trial estimated the effect of adding exercise classes, a spinal manipulation package , or spinal manipulation followed by exercise, to "best care" in general practice for patients consulting with back pain . RelativStrengths of our trial include the great number of subjects included and the relatively few dropouts, which led to a high internal validity. The kind of back and neck pain studied is very frequent, enabling a generalization of the results to a large proportion of the population. Another strength is that the results are presented with consideration taken not only to statistical significance, but also to clinically important changes in pain and disability .The trial was not designed to evaluate the different components in the compared treatments, but to compare a treatment with unknown effect  to a treatment with a well known positive effect (advice and support on staying active) on back and neck pain. Accordingly we cannot tell what in the naprapathic manual therapy that has a positive effect. Instead, the design enables a generalization of the results to outpatient clinics, something that we consider a strength. The treatment strategies differed regarding the number of treatments offered and the hands-on approach, which partly might explain the differences in outcomes between the groups. Nevertheless, another extensive trial of manual therapy for back pain had the same control treatment as in this trial. They found only small benefits from manual therapy. The choice of control treatment was in this case discussed as an explanation for the smaller differences between the groups than expected .We did not measure the subjects' expectations of the effect of the interventions before the trial started. A detailed explanation of the control intervention would have been like exposing all to this intervention. Before inclusion in the study, all potential study persons were asked why they considered participating. Sixty percent of the assigned wanted to see a naprapath, which may indicate an expectation bias.Typically, the most obvious effect of manual therapy is seen in the short term ,17,19. IWe plan to report on the more public health oriented outcomes as cost utility and sick leave as observed in the present trial, when such data have been analyzed.Compared to evidence-based care provided by a physician, naprapathic manual therapy implied a greater improvement in pain and disability for patients with non-specific back and/or neck pain in the short as well as in the long term. The trial adds to the knowledge that recommending a combination of manual therapies, as naprapathic manual therapy, may be an alternative to consider in primary health care for these patients. Since back and neck pain are among the most common reasons for seeking primary health care our results may be of broad interest and importance.The sources of funding had no influence on the design, the conduct or the reporting of the trial. The authors declare that they have no competing interests. ES is a part time employee at the Scandinavian College of Naprapathic Manual Medicine and a scientific advisor to the Swedish Naprapathic Association. LA is a scientific advisor to the Scandinavian College of Naprapathic Manual Medicine. These potential conflicting interests has not influenced the interpretation of data or presentation of information in studies based on the trial.The authors ES, EV and LA have made substantial contributions to conception and design of the trial, acquisition and analysis of data. ES and TB are the main authors and EV, LA and LH have all been involved in interpretation of data, drafting the manuscript and revising it critically. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/26/prepub


To explore how chronic musculoskeletal pain is managed in multidisciplinary pain clinics for patients for whom physical interventions are inappropriate or ineffective.A qualitative study was undertaken using semi-structured interviews with twenty five members of the pain management team drawn from seven pain clinics and one pain management unit located across the UK.All clinics reported using a multidisciplinary bio-psychosocial model. However the chronic pain management strategy actually focussed on psychological approaches in preference to physical approaches. These approaches were utilised by all practitioners irrespective of their discipline. Consideration of social elements such as access to social support networks to support patients in managing their chronic pain was conspicuously absent from the approaches used.Pain clinic practitioners readily embraced cognitive/behavioural based management strategies but relatively little consideration to the impact social factors played in managing chronic pain was reported. Consequently multidisciplinary pain clinics espousing a bio-psychosocial model of pain management may not be achieving their maximum potential. Chronic pain is a complex experience influenced as much by patients' social and cultural environment, beliefs, expectations, attitudes, and the meanings they ascribe to their pain, as it is by biological factors. As such, biomedicine's historical concept of chronic pain as having an organic basis requiring a specific bio-medical intervention, has increasingly given way to treating chronic pain as a bio-psychosocial phenomenon requiring integrated, multidisciplinary treatment ,2.This treatment approach considers chronic pain to be caused by a dynamic interaction between patients' physical, psychological and social influences shaping their responses to the pain . IncreasA model integrating both psychological and physiological processes facilitates an understanding of pain and informs the bio-psychosocial approach to managing chronic pain ,8-11. SuA qualitative approach was used to capture the processes and procedures used in varying organisational clinic settings and the beliefs and expectations of multidisciplinary team members in managing chronic pain patients for whom physical interventions were either ineffective or not appropriate.We conducted semi-structured interviews with 25 members of the multidisciplinary team representing medicine, nursing, physiotherapy and psychology drawn from seven hospital-based pain clinics and one pain management unit*.* Pain clinics offer various multidisciplinary treatments, including cognitive based therapies, injections and prescribing medicines and are characteristically led by doctors. Each of the pain clinics sampled offered a range of individual therapies. Pain management units offer psychologically-based rehabilitative treatment for people with chronic pain and are typically led by clinical psychologists. The pain management unit we sampled offered both group based and individual pain management programmes.Configuration of pain clinics and composition of their teams vary across Britain and their clinical lead may be drawn from differing medical specialities. In order to ensure a broadly representative sample the clinics were purposively selected to incorporate those led by anaesthetists, rheumatologists, and combined rheumatologist/anaesthetist clinics, and were geographically distributed across four NHS regions of the UK North-East, North West, London and South West. No clinic we approached declined to participate. Included in this sample was a pain clinic from which, in our previous study we had drawn a sample of patients to explore their perspectives on pain management. Interviews lasted approximately 30 minutes and were conducted during working hours in the clinic, by appointment with practitioners between clinic commitments, and undertaken by a social scientist (GH) experienced in qualitative interviews around chronic pain issues. Interviewees were largely self-selected following an open invitation to all team members, and a request for at least one member of the constituent disciplines represented in each clinic. We were therefore able to access the perspectives of physicians, physiotherapists and clinical psychologists comprising the core team of each clinic. Some clinics also included nurse specialists and acupuncturists and these were included in our overall sample.The interviews were conducted around a topic guide, developed in part from our previous systematic review and study of pain clinic patients ,15 and cInterviews were tape recorded and transcribed. Semi-structured interviews limited the opportunity for open ended questions but interviewees were invited to articulate their developed thoughts where appropriate, particularly with regard to managing patients with complex problems. We continued interviews until the emergent themes from the data were sufficiently conceptualised as to not warrant further interviews.Textual analysis of the interview transcripts commenced with the construction of a thematic framework to identify key issues and construct concepts. The data were systematically coded, and synthesised by theme . The proOur participants covered the spectrum of staff working in pain clinics Table . Four thAnalysis of these themes  exploredFor patients assessed by specialist clinicians in pain clinics, failure to identify an underlying physical cause and exclusion of the potential for biomedical treatment impacts on the relationship between the clinician, the patient, and their pain. In such cases the pursuit of a 'cure' or even the possibility of a marked reduction in pain may be discounted by clinicians. While some practitioners report that patients engage with the notion that a cure is not possible, others present more of a challenge for the team to manage. For these the team's task was to shift patients' attention away from relieving or reducing pain by biomedical interventions, towards living with and adapting to pain.one of the things we try to ...err... help patients to understand is that this is a different kind of treatment insofar as we're giving them skills to help themselves and it's no longer a medical context in which things are done to them...we do try to empower patients to learn skills which will enable them to be in control of their chronic condition...We tell people we're dealing with the problems the pain causes, rather than the pain itself. Psychologist (Archie)The consultation's focus moves from the pain itself as the problem, towards the patients' responses to the pain. For clinicians the imperative becomes one of moving the patient away from passive dependency on biomedicine for a cure or marked reduction of their pain, towards active dependency on the pain clinic as a source of the skills and abilities necessary to enable the patient, upon discharge or completion of their programme of therapy, to cope with their pain and not continue to seek further consultations....we're not working on a medical model, trying to cure people, we're teaching people how to manage their pain and return to a normal lifestyle. So many people come here thinking it's the last resort and they've got nothing to lose really... and they start the education process that they'll suddenly turn round and say, ... this should be happening early on. Physiotherapist (Andrew)The clinic team therefore serves an educational function for patients - the objective being to adjust the patient's model of pain from one in which there is a medical 'cure', to one in which the patient is educated to accept that the pain will not necessarily be cured and that ability to manage this pain has a psychological element. This model centres on arriving at a concordance of understanding of chronic pain. This involves setting a clear agenda for chronic pain patients in which the notion of a medical cure for their pain is, in the context of the pain clinic, inappropriate. Rather, the pain clinic team's objectives are to facilitate patients to take responsibility for their own pain management. This requires the team to work with a model of pain that acknowledges the biomedical basis of chronic pain but is not evoked in the consultations with the patient. Instead a psychological model of pain is the central focus of the consultation, with psychosocial interventions such as acceptance, planning, support, limits, and learning to pace physical activities playing an important role.Instruction into the skills necessary to cope with and adapt to their chronic pain, then, becomes a central part of the bio-psychosocial approach. However, it was widely reported that some patients want to get rid of their pain - not confront it. The clinic staff therefore have to work towards getting patients 'on side', which invariably translates as preparing the patient to take responsibility for their pain - assuming other than a paternalistic, dependent bio-medically based relationship.I think education, reversal of physical de-conditioning and improvement of quality of life and coping skills are the important things. I'm not particularly concerned whether I decrease their pain score or not and I would hope by the end of the episode, the treatment episode, the patient feels the same way. So it's really sharing a shared model of what their pain is, and what's important to them is very important, so if they don't see it the same way that you do you're not going to get very far. Anaesthetist (Barry)It was evident that most, if not all team members, assumed patients come to the clinic with a sense of dependency which the staff had then to wean them off. This assumes also that they would not wish to be involved in their pain management but have to be encouraged to do so, and further, that patients need to be convinced of an alternative to the biomedical approach. The objectives of the clinic then are to try and encourage patients to understand their chronic pain as an entity which cannot be cured by biomedicine and to foster a new perspective on their chronic pain.The challenge for the team is not simply to educate patients in a set of skills and coping techniques for patients who otherwise expect a cure or a reduction in their pain, but to enable patients themselves to work towards changing their perspective on their pain....it's not just about giving people strategies, it's about helping people through that process whereby they can accept that pain will happen to all of us and in some cases pain will remain with some people and that it isn't that they're being singled out, I think it is more of a philosophical stance perhaps that we're trying to help people explore. Psychologist (Dawn)...what we're trying to do is give them a compelling story that suggests to them they shouldn't even try the physical stuff. Pain Management Consultant (Harry)For the patient, exploring this philosophical stance may involve a lengthy process of coming to terms with chronic pain and accepting the limitations of biomedicine. Within the time constraints of the clinic, devising means of engaging patients with this process at the outset involved a variety of strategies most often instigated by the lead clinician Patients presenting to pain clinics may have already been screened for any obvious underlying physiological causes by the referring medical practitioner and/or allied health professional. The initial assessment of such patients in most pain clinics was undertaken by the lead clinician  - invariably a consultant anaesthetist whose role included diagnosing conditions requiring medical interventions and where appropriate distinguishing these from cases assessed to require rehabilitation.Where a purely interventionist biomedical approach (injections etc) was deemed inappropriate, management of patients with chronic pain was directed by a holistic bio-psychosocial model.Every patient I see has a full bio-psychosocial assessment by me, so not by a physiotherapist and not by a psychologist, but I'm experienced in assessing patients that way and I'm perfectly happy to consider the patients' problem to be largely psychosocial, psychological, or social, or biological, depending on what the problem is. So I don't have any weighting in my assessment. Anaesthetist (Barry)A key element of this model is its emphasis on the patients' cognitions concerning their pain. This process of re-framing a condition from something that can be resolved or markedly reduced by medical intervention, to that of a more complex condition requiring a multidisciplinary approach to assist the person in learning to cope with it requires pain clinic practitioners to carefully manage patients who may otherwise interpret this reframing as tantamount to being abandoned by biomedicine with an associated loss of hope for improvement.there's nothing more I can do, I'm sending you to our physio, in practice patients' chronic pain was re-framed as a cognitive problem. Specialist lead clinicians trained in interventionist medicine, whilst aware of the boundaries of their knowledge of cognitive based treatment, may have limited expertise in assessing cognitive conditions, compared with clinical psychologists.Undertaking a bio-psychosocial assessment and sanctioning this multidisciplinary treatment model reflects the complex nature of managing chronic pain for which there is no attributable, underlying physical cause. It was evident from pain clinic practitioners we interviewed, that while they espoused a holistic approach - combining multiple disciplinary approaches rather than an incremental approach i.e. I think I can do a basic psychosocial assessment and determine whether that's an important component of the problem, but I wouldn't feel comfortable taking it any further than that.... Anaesthetist (Barry)Moreover their role in the clinic for many is part time and distinct from their other medical diagnostic role. Others regard their experience in managing chronic pain as equipping them to cross boundaries and assume a dual role - as both diagnostic clinician or practitioner and cognitive-based therapist.I may be leaning more towards the psychological approach as well, whereas I do perform injections and I do all that, and I do quite a lot of injections and tablets etc, etc. I also work every other week with psychologists in a combined clinic, so my way of looking at things, I think, is very much determined by my ongoing experience there. .. So I look at a bio-psychosocial assessment as the crux of assessing any patient. Anaesthetist (Alicia)...sometimes I think of myself as a psycho-physiotherapist, I'm very clear that I'm not a psychologist, so when somebody presents with something difficult I just say, okay, that's very interesting, but I can't really talk to you about that, don't really know where to go with that. But if they say I just can't get round to doing anything, then I feel that you need to be a psycho-physiotherapist to get round that, to do with motivation, as I have in that area quite happily...I think we tend to be tellers - stand up, sit down, lift your leg up - and I like being an asker, I think I've learnt to be an asker. Physiotherapist (Eugene)Assessing patient need as requiring either intervention or self-management (rehabilitation) or both is therefore determined by practitioners whose primary expertise is interventionist  and who assess patients with little or no input from other members of the team. Thus there was some acknowledgement that part-time pain clinic clinicians were perhaps not necessarily best placed to assess chronic pain patients' holistic bio-psychosocial status.I think fairly few skills I've got from anaesthetics are in any way appropriate to pain management - sticking needles in is probably about it and that's a very small part of my practice...I think that's one of the big faults of pain management in this country is that we do it part-time. Anaesthetist (Errol)Indeed a number of investigators ,22 recomI think very often you have just a little bit more time with the patient to listen to their side of the story and talk round the subject, rather than indoctrinating them and telling them to go away and what to do, you listen more to what the patient's fears and problems are to help them overcome them themselves really. Physiotherapist/Acupuncturist(Doreen)I think there are lots of psychological stuff and behavioural stuff that you can do with people that will make their lives better. And you sit down from them and you try and figure out what the story is - and the story is often very complicated and often I've got no idea where it's going to start with. But you look for the weaknesses in their story or the problems that they're having, and they're often very psychological. Physiotherapist (Eugene)In these instances chronic musculoskeletal pain is framed as a problem of the patients' cognitions, expectations and beliefs. Physiotherapists, nurses and others we interviewed processed patients by drawing on psychological models - and "narrative reasoning" - approaches more closely identified with specialist clinical psychologists . AlthougA patient perceiving the clinic as the 'end of the treatment road' has implications for their management, particularly when no biomedical intervention is appropriate. Managing the care of such patients is challenging as the patient's expectations may differ from those of the multidisciplinary team. Having a shared agenda which recognises the inappropriateness of biomedical interventions and favouring instead a psychosocial approach, remains the biggest challenge, for practitioners and patients.The first thing is to identify with the patient what they want ... err ... which may sound silly, because they attend the pain clinic to get rid of pain. ...And once you've established that they've got chronic pain, you then take them through the journey of symptom management, so you look at what's been tried in the past, what may be worth trying in the future, so we don't abandon all hope straight away. And at the same time we're also looking at the longer term pain management strategies, so getting them to pace themselves, learning to manage pain better, be more in control of it, how it affects them and relationships and social life and work and all these things. Anaesthetist (Derrick)This was especially so for some physicians whose stated aims for these patients were to relieve or reduce their pain. When this is not realistic it became necessary to shift patients' expectations towards a focus on coming to terms with their pain by developing coping strategies. This shift of focus away from biomedical interventions was considered by team members to be interpreted by some patients, fearful of being discharged, as indicative of being abandoned, and brought into sharp relief potential differences amongst multidisciplinary teams. Some clinics responded with a policy of not discharging patients but rather maintaining an open-ended relationship based on ongoing support for self-management and independence. Others were blunter with those patients with persistent unrealistic expectations:I'll be as blunt as I need to be, I'll say, look, we've done everything we can to try and manage symptoms, we're not going to win. And you present them with the bio psychosocial model, where you say, right, the bio bit doesn't work, so we can look at the psycho bit and the social bit, if you don't want to buy into that then we can't offer anything. Anaesthetist (David)occasionally you do have to poke them in the eye with, I'm sorry, this is where I think it should stop. Rheumatologist (Bernard)..This blunt approach was particularly characteristic of some clinicians who triaged such patients as not suitable for intervention, and anticipated patients disappointment at what might be considered abandonment by bio-medicine.Central to all clinics' management strategies was validating patients' sense of hope - hope for help with their pain - not necessarily reducing it but developing rehabilitation strategies to improve their quality of life. This necessitated establishing patient expectations - some sought only a diagnostic label for their pain. An integral feature of managing patient expectations involved bringing the patients relationship with the clinic to a conclusion. Sometimes managing patients' expectations was more akin to a take it or leave it approach - which potentially serves to exacerbate a sense of abandonment. In this vein coming to terms with chronic pain was considered analogous to the process of bereavement.I think the most difficult patients are the ones where there's a disparity between the diagnostic and the management process, i.e. patients who after years of having had the chronic condition still seek a diagnostic confirmation of the problem and still seek out clinicians, often other clinicians, who still support an ongoing diagnostic process. Because a so-called successful voyage into dealing with chronic pain in my perception is that there needs to be a process of acceptance and a process of bereavement... Anaesthetist (Alicia)This analogy is particularly appropriate in that it acknowledges the transition from seeking relief or reduction of pain to coping with pain as a complex and often lengthy process - one which an interventionist biomedical model is inappropriate.While boundaries between health workers have undergone marked changes in recent years, the impact of these changes for the specialist pain clinic team is not known. A key feature of pain clinics is the multidisciplinary nature of their pain management programmes with all clinics applying a holistic, bio-psychosocial model of pain management in a professed non-hierarchical structure.I think we're all equal and different. Anaesthetist (Charles)I'll bring out the physical and physiotherapy aspects when, say, L  is doing her psychology bit. And she'll back up and if I'm doing the physical bit she'll say can you see how this influences the psychology? So we back each other up, there's one message going out. Physiotherapist (Betty)Multidisciplinary working potentially enables clinics to provide a level of patient benefit that collectively is greater than the sum of the individual team members' contributions. However, this style of working could also undermine the efficiency of the clinic's work. This stems from people working outside the area of their core expertise for which they are trained. Thus although the regulatory body for UK physiotherapists  endorsesWhere professional boundaries were retained, efforts were made to ensure patients experienced integrated rather than disparate care. This shared common purpose was especially evident in accounts of team meetings, whose proceedings were purportedly a forum for all members to contribute equally....every second week we do have a multidisciplinary meeting and everybody's given equal say. And certainly you never know what somebody's really thinking, I suppose. But certainly I get the impression that we're all aware that we have equally important roles to play. And the physiotherapists and nurses - and the managers - do attend our multidisciplinary meeting as well. So I do think its egalitarian. Anaesthetist (Barry)Respect for boundaries was clearly evident but with close working relations there was, albeit unwittingly, some boundary encroachment with, for example, physiotherapists managing some patients by drawing on behavioural psychological constructs. For lead physicians - particularly those with a psychology degree - whose management of chronic pain patients included a cognitive therapy approach - this was considered less a blurring of their traditional boundaries but more accurately a case of role expansion in that bio psychosocial model was perceived as an addition to their professional repertoire of roles - introducing a holistic as well as a purely biomedical assessment.... that's not to suggest that the consultants will give the medical opinions and the physios or other therapists or the nurses might give the psychological side, in fact quite the contrary, a couple of our consultants here have also got a degree in psychology, so they're obviously coming from that flavour as well. So it's for everybody just to chip in on what they think. Physiotherapist (Colin)Team members tended not to encroach on other's territory when initially assessing patients. Rather this assessment, although ostensibly a bio-psychosocial assessment was invariably undertaken by team members whose initial emphasis was on biomedical management followed in turn by psychosocial considerations....at assessment we think about all the 3 aspects and we are always thinking about them integrating. I think in reality - this is just my assumption - I think in reality, yes, they hit the biological first. But then why not, because that's their role - as a psychologist I would maybe get the psychology first. Psychologist (Ben)I work alongside the consultants and basically it's a mostly biomedical assessment in order really to get a reasonable diagnosis or to investigate further. Physiotherapist (Andrew)...the medics initially are after a pain cure, the psychologists aren't, we're after helping people to manage their pain, reduce their distress and live with life despite pain. I think once the medics have gone through their biological bit, can we help them with medication, injections, whatever, I think at that point we're then more all on board together about, okay, it's now time to manage it. Psychologist (Dawn)Notwithstanding issues regarding the cohesiveness of the multidisciplinary team in managing patients with chronic pain, all were united in sharing a clear sense of their role being misunderstood by referral agencies...for the vast majority of people who refer here this is considered to be where you go when you can't think of anything else to do. Anaesthetist (Alicia)You also see a lot of patients who are not adequately investigated before they come here, the important point being we should not be a diagnostic clinic, we're a symptom control clinic, we're a pain management clinic Anaesthetist (Barry)to patients and instead facilitating patients to adopt behavioural and psychological changes enabling them to self-manage their pain. In addressing this challenge we found the multidisciplinary team's management strategies focused on the psychological domain of the bio-psychosocial model. Whilst this aspect of patients' management might logically belong to specialist clinical psychologists, the ethos of pain clinics as multidisciplinary leads its members (irrespective of lack of appropriate training or otherwise in psychology) to embrace psychological constructs as part of their patients' management plans - a position endorsed by some professional ruling bodies.The application of the bio-psychosocial model for chronic musculoskeletal pain management reflects the complex, multi-levelled nature of chronic musculoskeletal pain. There was an impressive consistency in rhetoric from all team members espousing an integrated bio-psychosocial approach to chronic pain management, though some doctors had problems integrating the physical and psycho-social approaches with the traditional bio-medical model. There was less consistency in opinions about how this should be applied and the psychological elements of the approach predominated. The challenge for the team is to move from doing something However, the model is open to various interpretations. For most, there was a sense that because the patient had been assessed as not appropriate for interventions - by default the management strategy was to focus on the cognitive and behavioural factors - working to rehabilitate patients by altering their expectations and help them develops effective coping strategies. As a result, team members whose core discipline did not encompass cognitive and behavioural elements, such as physiotherapists, physicians and nurses, alongside professionally qualified clinical psychologist experts in cognitive behavioural strategies incorporated these into their management plans.For some practitioners, managing patients using the bio-psychosocial model leads them to downplay their biomedical disciplinary background in favour of dealing with the patient's chronic pain by addressing their beliefs, expectations and behaviours. Key to this is an assumption that people with chronic pain for which there is no biomedical intervention suitable for their chronic pain would benefit from being "taught" a set of cognitive-based skills as an integral feature of their rehabilitation programme. Consequently the bio-psychosocial model is adopted only partially with most attention given over to cognitive and behavioural factors - coping strategies, and commensurately less to social factors such as the nature, character and level of social support patients are able to access to assist in managing their chronic pain.Notably absent from the accounts was any acknowledgement or detailed account of how practitioners managed the social aspects of chronic pain i.e. addressing issues relating to how patients social interactions was affected by their chronic pain. For example, issues relating to social support, sense of identity and stigma associated with being a chronic pain sufferer were revealed in our earlier study of patients' perspectives, but these were not broached in any detail among the practitioners interviewed. This contrasts with detailed accounts from a range of practitioners reporting how patients' cognitive and psychological therapeutic needs were managed. It is plausible that implicit in these accounts the patients' social needs were also considered by practitioners. However this was not elaborated upon and there were no accounts framing patients' chronic pain management as requiring consideration of both the patients' cognitive and social adaptive strategies. Whilst this is a feature of many structured pain management programmes which invite participation by patients' relatives (including the pain management unit sampled), it was not evident in the accounts from pain clinic practitioners.a form of influence based not on coercion but rather on "the normal and easy 'way things go" in the organisation" [Partial adoption of the bio-psychosocial model in which the pain clinic team members manage chronic pain primarily as a cognitive/behavioural issue as the accepted interpretation of this model is reminiscent of a form of medical hegemony i.e. "isation"  in that Many of the social aspects of chronic pain, such as housing or financial issues cannot be managed within a hospital clinic as they do not lie within the remit of healthcare professionals in the UK. Even so, clinics were all committed to a bio-psychosocial management strategy promoted by lead clinicians and which serves to justify the application of a multidisciplinary approach in which the disciplinary boundaries of the team become less clearly defined. While this enables a unified team approach to chronic pain management, importantly, variations in its interpretation mean that social factors impinging on patient's ability to manage their chronic pain may be given less consideration in a management pathway emphasising cognitive processes.It is possible that among the practitioners we interviewed, they assessed a sole psychological approach to be most appropriate for patients for whom interventions were inappropriate or ineffective to self manage, having already considered any relevant social components. That they did not articulate which modalities of the bio-psychosocial model they discounted in arriving at a management strategy does not indicate a propensity towards only a cognitive based approach. However, it was the approach utilised by all members of the multidisciplinary team. This would suggest consideration of social factors impacting on chronic pain management strategies were assessed as not as significant and/or relevant to the teams' therapeutic approach. Alternatively it could represent a default approach to which all team members subscribe. If so, this might diminish the potential of a multidisciplinary model for managing patients whose chronic pain is not responsive to interventions or is not considered appropriate.Although this is the largest qualitative study to look at the beliefs of staff who manage patients with this problem across a range of clinics and disciplines, our findings may not reflect processes of all pain clinics and professionals both within the UK and in other countries.Nonetheless the subjects of this study consistently espoused a bio-psychosocial approach to patients with chronic musculoskeletal pain for whom medical interventions were inappropriate. Educating patients to move from expectating a cure for pain and towards learning to live with pain were important goals of the team's work. This concurs well with the views of patients identified in our previous study . We haveThe authors declare that they have no competing interests.GH and MU conceived the study and GH led on its design. GH collected and undertook the initial analysis of the data, drafted the manuscript and its subsequent revisions. MU, AR SP and JC participated in the study's design and contributed to revising the manuscript. SP contributed to validating the analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/51/prepub


Musculoskeletal symptoms including arthralgia and myalgia occur frequently in aging women, particularly during the transition to menopause, when plasma estrogens precipitously decline. In postmenopausal women (PMW) with breast cancer, third-generation aromatase inhibitors (AIs) as adjuvant hormonal therapy have proven to be more effective, and to have a more predictable side effect profile, than tamoxifen. However, AIs further reduce plasma estrogens in PMW, exacerbating musculoskeletal symptoms. Clinical trial data have shown significantly higher incidences of arthralgia and myalgia with AIs compared with women on tamoxifen or placebo. Symptoms may be severe enough to significantly affect quality of life; musculoskeletal symptoms are a frequent reason for discontinuing therapy. In many cases, symptoms can be effectively managed with oral analgesics or other strategies. Early recognition and effective management of musculoskeletal symptoms can help maximize treatment compliance, enabling patients to derive optimal benefit from therapy in terms of preventing recurrence. The third-generation aromatase inhibitors (AIs) have proven superior to tamoxifen when used as adjuvant hormonal therapy in postmenopausal women with hormone receptor positive (HR+) early breast cancer. Major trials have established that AIs improve disease-free survival (DFS) when used either as initial adjuvant therapy or as a switch/sequential option for patients completing 2 or more years of prior tamoxifen treatment –4, and tN = 12) or tamoxifen (N = 5) found that after 6 months, AI users were >2-fold more likely to have decreased grip strength compared with tamoxifen users , and >3.5 times more likely than tamoxifen users to have magnetic resonance imaging (MRI)-assessed worsening of tenosynovial changes  . Hi. Hin = 8amoxifen  24]. Th. Thn = 8Taken together, these studies suggest that the profound suppression of estrogen by AIs in postmenopausal women can result in an exacerbation of menopausal symptoms and the emergence of musculoskeletal AEs, both in the initial adjuvant setting and in those who have received prior tamoxifen treatment. Despite these findings, however, clinical trials of AIs have failed to find a significant worsening in QoL measures for patients on AIs relative to tamoxifen or placebo, suggesting no apparent measurable impact on day-to-day function and activity, even if patients were experiencing musculoskeletal symptoms while on AIs –35.N = 612), the most commonly reported side effects were joint-related , and the AI discontinuation rate was 30%, with 84% of these patients discontinuing therapy primarily because of joint-related symptoms [N = 200) receiving AI treatment for breast cancer  [N = 56) found new or worsening symptoms in 61% of the patients, with a severity of 7.5 on a 10-point scale; notably, 30% rated their pain as 8−10, and the discontinuation rate was 20% for arthralgia [Evidence from patient-perspective studies indicate that joint aches are among the most troublesome symptoms for patients taking AIs. In a large study of AI-related side effects N = 6, the mosmestane) . These ithralgia . There wA temporal relationship between new-onset pain or the worsening of preexisting pain and the initiation of an AI makes the diagnosis of AI-related arthralgia or myalgia rather straightforward. On physical examination, there is absence of the inflammatory findings typical of arthritis . Patient OTC pain medications, including acetaminophen and ibuprofen, are effective therapies for minor arthralgia and myalgia symptoms and are appropriate initial therapies for symptoms of acute joint pain . Many wo Switching between endocrine therapies may be another option for patients whose symptoms are troublesome, persistent, and/or not effectively managed with OTC pain medications. One such strategy involves switching to another AI. This option may be preferable for many patients, as the superior efficacy in preventing recurrence with AIs over tamoxifen is retained.P = .0192) or anastrozole (P = .0126), and three quarters of patients who experienced joint symptoms while on an AI did not have the same problems on tamoxifen. Notably, more than half of the patients with symptoms on one AI did not have the same problems on the other AI, suggesting that switching therapies could improve symptoms for some patients [N = 179) who experienced severe joint pain requiring discontinuation while on anastrozole were switched to letrozole [P = .04). Age, menopause duration, sociodemographic status, and previous osteoarthritis had no impact [P < .001), and QoL measures were significantly improved [The impact of the nonsteroidal AIs (letrozole and anastrozole) on joint pain and stiffness was examined in a randomized adjuvant trial . There wpatients . In the etrozole . Patiento impact . Fewer wimproved . These r Simple, low-cost, or no-cost lifestyle changes have been suggested to improve women's bone health and reduce the risk for osteoporosis. These changes include increased physical activity, load-bearing exercises, smoking cessation, and the avoidance of excessive alcohol and caffeine . The samN = 56) has reported the efficacy of glucosamine in 15% of patients with AI-related arthralgia and/or bone pain [ One small series (one pain . Glucosaone pain . MoreoveP < .0001), joint stiffness (P < .0001), and joint functional symptom interference (P = .0001) were observed with the intervention. The procedure was well-tolerated, and there was also significant improvement in fatigue (P = .005) and anxiety (P = .014) end points examined [ A single-arm feasibility trial has been conducted to determine whether electroacupuncture of affected joints  could reduce pain and stiffness in patients with AI-related arthralgia . Using texamined . Althougexamined . Vitamin D deficiency is associated with a syndrome of musculoskeletal symptoms with generalized nonspecific musculoskeletal pain and stiffness, as well as impaired muscle strength and function that is similar to that induced by AI therapy. Hypovitaminosis D has been suggested as an underlying etiology in individuals with persistent, nonspecific musculoskeletal pain . In addiP = .008, Mann-Whitney test). In addition, more women with 25OHD levels > 66 ng/mL (median level) reported no disability from joint pain than did women with levels < 66 ng/mL . We concluded that vitamin D deficiency and insufficiency were prevalent in postmenopausal women initiating adjuvant AI. Vitamin D3 supplementation with 50,000 IU per week was safe, significantly increased 25OHD levels, and reduced disability from AI-induced arthralgias. A randomized trial to confirm suggestions of a vitamin D protective effect against AI-associated disability from joint pain is underway . Interestingly, our results contrast with those of Dizdar et al., who found significantly higher levels of 25OHD in patients receiving AIs with arthralgia symptoms versus those without symptoms (P = .001) or control patients not receiving AIs (P = .005) [We conducted a pilot study to assess the prevalence of suboptimal vitamin D levels in 60 women initiating adjuvant letrozole for breast cancer, and to determine whether supplementation with 50,000 IU of vitamin D3 weekly could reduce musculoskeletal symptoms in women with suboptimal vitamin D levels . Baselin = .005) . DiffereMusculoskeletal symptoms are frequent in women treated with AIs and may adversely affect compliance with this class of medications. The major clinical trials of the AIs have been inconsistent in reporting musculoskeletal events and have likely underestimated the incidence, in view of the findings from clinical practice. In addition, the evaluation of joint symptoms remains largely subjective, and there is a need for more standardized assessments. Further research is needed to understand the exact mechanism and pathophysiology of this side effect. To date, there are no proven treatment interventions. Early data on vitamin D supplementation look promising, and results from a larger, ongoing phase III trial are awaited.


Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group.61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds , the heat and cold pain thresholds  and the occurrence of paradoxical heat sensation (PHS) were observed.In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb.We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system. Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder, evolving after limb trauma either without (CRPS I), or with definable nerve lesion (CRPS II) A sequence of disease symptoms has been described Several hypotheses about the pathophysiology of CRPS have been proposed emphasizing the importance of peripheral neurogenic inflammation Although sensory alterations accompanying CRPS can be assessed by quantitative sensory testing (QST) Therefore, we conducted a prospective study, investigating an unbiased sample of patients suffering from acute or chronic CRPS I of the upper extremity as well as an age- and gender-matched healthy control group. Patients with CRPS II or CRPS of the lower extremities were excluded, since the probable pathophysiology of CRPS I differs from CRPS II, and sensory thresholds of upper and lower extremities differ significantly Over a period of nine months, 61 consecutive patients presenting with the diagnosis CRPS I of the upper extremity  agreed to participate in the study. The diagnosis CRPS I was established by experienced examiners according to the research diagnosis criteria proposed by Bruehl All tests were performed under minimal distraction in a silent, air-conditioned room, with an ambient temperature of 25–26°Celsius. Subjects were seated on a comfortable chair, and allowed to adapt to the test environment for at least 20 minutes. QST followed a standardised protocol as described by Rolke and colleagues Thermal testing was performed using a Medoc Thermal Stimulus Analyser TSA-2001 device  using a computer-controlled Peltier-based probe. The basic principles of the Peltier stimulator are described in detail elsewhere Warm detection threshold (WDT), cold detection threshold (CDT), thermal sensory limen (TSL), cold pain threshold (CPT), and heat pain threshold (HPT) were measured using the method of limits as follows: For determination of WDT, CDT, CPT and HPT, subjects were applied three successive stimulations starting from a baseline temperature of 32°C. The rate of temperature increase or decrease respectively was 1°C/s. For WDT and CDT, subjects were instructed to press the response button as soon as sensation of cold or warm was detected. For detection of CPT and HPT the patients pressed the button to indicate the onset of cold pain or heat pain. After the button was pressed, the temperature returned immediately to baseline. For safety reasons, the minimal and maximal temperatures allowed were 0°C and 50°C to avoid tissue damage. If the individual pain threshold was not reached within these confines, 0°C or 50°C were assigned as surrogate pain threshold measures. A computer-generated random interval ranging from five to fifteen seconds was intercalated between stimulations. TSL was estimated as the difference limen for cold and warm thresholds when cold and warm stimuli were given in alternating order. For this reason, six alternating warm and cold stimuli were applied without returning to the baseline temperature. Patients were instructed to press the test button when a warm or cold sensation was felt. Subjects were also asked to identify the quality of the sensation at any time a cold or warm stimulus was given. Identification of a cold stimulus as either hot or burning pain was denoted as the occurrence of paradoxical heat sensation (PHS) Center for Epidemiological Studies Depression Test (CES-D). This test combines twenty questions designed to measure levels of depression In patients presenting with CRPS, clinical data were assessed with a standardised protocol obtaining data on the magnitude of pain, edema, skin temperature and levels of depression. Pain ratings were assessed by means of a numeric rating scale (NRS) from 0 to 10. Patients reported the pain level in the ipsilateral hand at the time of presentation. Furthermore, the presence or absence of edema was evaluated by the examiner in a dichotomous way (yes/no). Skin temperature was measured in three consecutive tests on the dorsum of each hand, applying infrared thermometry . Symptoms of depression were assessed by means of the German version of the Demographic and clinical data were compared using an unpaired t-test. Gender proportions as well as the presence of edema were tested by Yates-corrected chi-square. Kolmogorov-Smirnov's test was performed to assess deviations from normal distribution in demographic data.For analysis of WDT and CDT, the mean of the three measurements of temperature change from the baseline temperature of 32°C was calculated. Likewise, TSL was calculated as the mean difference between cold and warm thresholds at alternating stimulation. CDT, WDT and TSL data were transformed into decadic logarithms to achieve secondary normal distributions of these data. For CPT and HPT the arithmetic means were used for analysis. Data were analysed by two way analysis of covariance (ANCOVA) with the main factors: group  and body side , and the covariate age in order to control for the known age-dependency of somatosensation control)/SDcontrol. This operation rendered all z-transformed data directly comparable in units of SD of the control group. Z-transformed data were analysed by four way analysis of covariance (ANCOVA) with the main factors: group , body side , sensory dimension (nociceptive vs. non-nociceptive), and thermal modality (hot vs. cold) and the covariate age.Data were also normalized relative to the mean and standard deviation (SD) of the control group (z-transformation) according to the formula: z = .The impact of the presence or absence of PHS was also analyzed by two way analysis of covariance (ANCOVA) with the main factors: PHS (PHS+ vs. PHS−) and body side , and the covariate age. In addition, all parameters were entered into a forward stepwise multiple regression equation, in order to identify which parameters significantly predicted the occurrence of PHS. A probability level of p<0.05 was considered significant, p<0.10 was considered a significant trend. All analysis was performed using the STATISTICAThere was no difference in mean age between CRPS I patients and healthy subjects, both groups exhibited normal distributions of age. CRPS duration, however, exhibited an obvious bimodal distribution , Table 2No differences were found concerning the levels of pain as well as depression between acute and chronic CRPS patients . However2,113 = 30.04, p<<0.0001), body side  and group x side interaction  for the cold detection threshold (CDT). In healthy control subjects, CDT was highly correlated  and very symmetrical between body sides   revealed a highly significant effect of group (F = 0.88) . In cont = 0.88) . CDT in  = 0.88) . Thus, p2,113 = 27.66, p<<0.0001, body side: F1,113 = 13.12, p<0.001, and group x side interaction: F2,113 = 4.22, p<0.05), loss of symmetry , and deterioration of correlation between sides (r = 0.56 vs. r = 0.35) (Warm detection thresholds (WDT) exhibited a similar overall pattern: ANCOVA (group: F = 0.35) . WDT was = 0.35) . Further = 0.35) . In aggr2,113 = 22.42, p<<0.0001, body side: F1,113 = 19.12, p<0.001 and group x side interaction: F2,113 = 10.36, p<0.0001) revealed a strong ipsilateral threshold increase in acute CRPS, even more increased in chronic CRPS . A similar pattern was observed in the contralateral hand  , assessed by alternating CDT and WDT, yielded the same results: ANCOVA (group: Fed hand) .2,113 = 7.33, p<0.001), but neither body side, nor group x side interaction were significant (both p>0.70). HPT was symmetrical in all groups (p>0.50 each) and significantly correlated between body sides although significantly less well in CRPS . HPT was significantly lowered in acute CRPS patients when compared to healthy controls . In chronic CRPS, however, HPT had almost normal values  exhibited a highly significant group effect in ANCOVA  and body side  in ANCOVA, but no group x side interaction (p = 0.22). High symmetry  and correlation in healthy subjects was not found in CRPS patients (r = 0.70 vs. r = 0.85) (p<0.05 vs. controls:)  exhibited a highly significant effect of group (Fntrols:) . Acute Cntrols:) .2,113 = 2.37, p = 0.07), indicating that overall side differences of sensitivity in CRPS patients were not marked. In contrast, a highly significant interaction for group x thermal detection vs. thermal pain was found  based on pronounced sensory loss  relative to the control group in acute CRPS, and even more pronounced in the chronic stage. In contrast, a gain  in thermal pain  was found, which was less marked in the chronic stage of CRPS  was based on more prominent sensory loss in thermal detection in the affected hand of CRPS patients. Separate ANCOVAs for thermal detection or pain thresholds of CRPS patients confirmed a significant asymmetry of loss in thermal detection , but not in thermal pain .The pattern of changes in different parameters of thermal sensitivity were compared in normalized data (z- transformed vs. control subjects)  of CRPS . A highlParadoxical heat sensations (PHS) occurred in only 1/336 TSL trials in both hands of healthy controls (0.3%). In contrast, PHS was a very frequent finding in the affected and contralateral hand in acute CRPS . PHS+ patients displayed significantly more cold pain hyperalgesia than PHS– patients , but no difference in e.g. heat hyperalgesia  or absence (PHS−) of PHS on any other sensory measure was explored. ANCOVAs (corrected for age) revealed no impact of PHS+ or PHS− on either CDT, WDT, TSL or HPT . In contrast, PHS+ and PHS– patients differed significantly in their cold pain thresholds , namely age , duration of acute CRPS , and CPT .As there is a vivid discussion about the pathophysiological mechanisms underlying CRPS I and II In the study at issue, a standardised protocol for thermal testing was used The distinction of acute vs. chronic CRPS was justified by a natural gap in an obviously bimodal distribution concerning duration of disease . FurtherBesides pain, acute CRPS is inter alia accompanied by edema, reddening and increased skin temperature. Any of these symptoms  suggest the presence of inflammation, and thus it has been hypothesized, that at least in the early phase, aseptic inflammation is a critical feature of CRPS In this study, the presence of heat hyperalgesia in the acute CRPS group indicates peripheral sensitisation of heat-sensitive C-fibre nociceptors, which is a hallmark sign of inflammatory processes Apart from signs of inflammatory hyperalgesia, our findings suggest a pronounced degeneration of thinly myelinated A-delta cold fibres as well as unmyelinated C warm fibres in acute CRPS. The degeneration hypothesis is based on a highly significant increase in warm and cold detection thresholds, indicating emerging A-delta and C-fibre dysfunction Apart from inflammation, the presence of cold hyperalgesia can also be explained by a second mechanism. This involves central disinhibition of cold-sensitive nociceptive pathways, namely by an degenerative insufficiency of A-fibre inputs to control nociceptive inputs, since cold hyperalgesia is reliable induced by experimental acute and selective A-fibre conduction blockade The hypothesis of cold pain hyperalgesia being caused by a combination of inflammation and A-delta-fibre degeneration is emphasised by the incomplete recovery of CPT in chronic CRPS. Heat hyperalgesia, which is mainly caused by inflammatory C-fibre sensitisation, resolved almost completely, as suggested by a return of HPT to almost normal values in the chronic stage of the disease. At the same time, significant cold hyperalgesia persisted in the chronic stage, when signs of axonal degeneration were even more pronounced see .Paradoxical heat sensation (PHS), i.e. a sensation of hot or burning pain to mild cold stimulation following a preceding mild warm stimulus, represents a disturbance of sensory integration in thermosensation. It is hardly ever present in the hands of healthy subjects  In chronic CRPS, symptoms of inflammation disappear, while neurological signs of small nerve fibre degeneration prevail. As discussed above, paradoxical heat sensation not only requires an A-delta fibre dysfunction, but is also more likely to occur when C-fibre input is increased, as in the condition of inflammatory peripheral sensitisation. In chronic CRPS, when clinical signs of inflammation subside, PHS was thus almost absent. Furthermore, no heat hyperalgesia was detectable, indicating the absence of a relevant peripheral inflammation. Additionally, cold as well as warm detection thresholds deteriorated, indicating a further impairment of small fibre function. This is in order with a recent study by Oaklander and colleagues, showing that CRPS I leads to small fibre axonal degeneration Unexpectedly, in acute as well as in chronic CRPS I, QST-results revealed changes in the contralateral hand, which mirrored the sensory changes in the hand primarily affected by the disease. These changes were not always as pronounced as the alterations on the ipsilateral (affected) side. Namely, there was a lesser degree of loss of cold and warm detection. Notably however, hyperalgesia in acute CRPS was equally pronounced on the ipsilateral as well as on the contralateral side. This might necessitate the conclusion, that inflammatory hyperalgesia is not limited to the affected limb. This may be related to an exaggerated level of neurogenic inflammation, since an increased axon reflex vasodilation has been shown to occur in the contralateral hand of former CRPS patients QST is a behavioural functional measure of sensory function. Thus, it does not provide direct evidence of either structural loss of axons innervating the tested area or phenotypic changes of sensory nerve fibers.So far, epidermal nerve fibre density and Quantitative Sensory Testing show only weak correlations In the absence of structural changes, an increase in thermal detection thresholds can also result from functional impairment of a sensory pathway. Particularly, tactile but also thermal sensitivity is modulated dynamically by nociceptive input, and hypoaesthesia secondary to clinical as well as experimental pain conditions has been delineated Furthermore, the involvement of supraspinal changes must be taken into account, particularly in order to understand the contralateral spread of symptoms. This is important, since thalamic as well as cortical reorganisation has been demonstrated to occur in patients suffering from CRPS I As a note of caution to the interpretation of our data, however, the degree of cortical reorganisation in the respective studies seemed to be associated with an impairment of tactile discrimination and was well correlated with the extent of mechanical hyperalgesia In conclusion, the present QST results suggest that in acute CRPS I, aseptic neurogenic inflammation accompanies or even initiates tissue changes, precipitating peripheral sensitisation and thus leading to hyperalgesia. Concomitantly, the same fundamental process may also initiate a hitherto unknown sequence of responses that eventually lead to the degeneration of small fibres. The exact time course of these events is not delineated yet. However, in chronic CRPS I, inflammation and ensuing signs of peripheral hyperalgesia subside, while at the same time, the degeneration of A-delta and C-fibres might further progress. It is unknown, whether this represents a final stage of trophic changes. All QST changes were, to a lesser degree, also present in the contralateral limb, indicating that pathophysiological changes in CRPS I might also be subclinically present in the extremity which is not primarily affected by the disease.