Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. OBJECTIVES: To define recovery from the patients' perspective and better understand their priorities for treatment approaches. METHODS: Establishing an international consortium, we used a 2-Round Delphi-based study in eight countries across Europe and North America. Participants ≥18 years who met, or had met, Budapest clinical criteria were included. Round 1 participants completed the statement: 'I would/do consider myself recovered from CRPS if/because…' alongside demographic and health questionnaires. Data were thematically organised and represented as 62 statements, from which participants identified and ranked their recovery priorities in Round 2. RESULTS: Round 1 (N = 347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily living; bodily functions; external factors; participation and personal factors. The top five priority statements in Round 2 (N = 252) were: no longer having (1) CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of movement, (4) need for medication, (5) stiffness in the affected limb. With very few exceptions, priorities were consistent, irrespective of patient demographics/geography. Symptoms affecting daily activities were among those most frequently reported. CONCLUSIONS: Our data showed a small number of themes are of highest importance to CRPS patients' definition of recovery. Patients want their pain, movement restriction and reliance on medication to be addressed, above all other factors. These factors should therefore be foremost concerns for future treatment and rehabilitation programmes. SIGNIFICANCE: Those with longstanding CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining recovery is therefore problematic in CRPS. Our study has identified patients' definition of recovery from CRPS, in order of priority, as relief from: their CRPS-related pain, generalised pain, movement restriction, reliance on medication, and stiffness.

Brain dynamics for perception of tactile allodynia (touch-induced pain) in postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a debilitating chronic pain condition often accompanied by a sensation of pain when the affected region is touched (tactile allodynia). Here we identify brain regions involved in stimulus-induced touch-evoked pain (dynamical mechanical allodynia, DMA), compare brain activity between DMA and spontaneous pain (described earlier for the same patients in [Geha PY, Baliki MN, Chialvo DR, Harden RN, Paice JA, Apkarian AV. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain 2007;128:88-100]), delineate regions that specifically code the magnitude of perceived allodynia, and show the transformation of allodynia-related information in the brain as a time-evolving network. Eleven PHN patients were studied for DMA and its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of pain while the affected body part was brushed during fMRI were contrasted with non-painful touch when brushing was applied to an equivalent opposite body site, and with fluctuations of a bar observed during scanning, at three sessions relative to Lidoderm treatment. Lidoderm treatment did not decrease DMA ratings but did decrease spontaneous pain. Multiple brain areas showed preferential activity for allodynia. However, mainly responses in the bilateral putamen and left medial temporal gyrus were related to the magnitude of allodynia. Both DMA and spontaneous pain perceptions were best represented within the same sub-cortical structures but with minimal overlap, implying that PHN pain modulates behavioral learning and hedonics. These results have important clinical implications regarding adequate therapy.

Prospective, randomized, single-blind, sham treatment-controlled study of the safety and efficacy of an electromagnetic field device for the treatment of chronic low back pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of therapeutic electromagnetic fields (TEMF) on chronic low back pain. Secondary objectives included the investigation of the effects of TEMF on psychometric measures. SETTING: Pain Research center in an Urban Academic Rehabilitation Facility. DESIGN: Prospective, randomized, single-blind, placebo (sham) treatment-controlled design in which participants were evaluated over a 6-week period. A total of 40 subjects were randomly assigned: 20 subjects to 15 milliTESLA (mT) treatment using a prototype electromagnetic field device and 20 to sham treatment. INTERVENTIONS: After a 2-week baseline period, eligible individuals were randomized to one of the treatment groups (sham or 15 mT) for six 30-minute treatments over 2 weeks, then a 2-week follow-up period. OUTCOME MEASURES: The primary outcome measure was the self-report of pain severity using a 100 mm visual analog scale collected using a twice daily McGill Pain Questionnaire-Short Form. Several secondary measures were assessed. RESULTS: Both groups (15 mT and sham) improved over time (P < 0.05). Although groups were similar during the treatment period, treated subjects (TEMF of 15 mT) improved significantly over sham treatment during the 2-week follow-up period (20.5% reduction in pain; F(1,34) = 10.62, P = 0.003). There were no reported serious adverse events. CONCLUSIONS: This study demonstrates that TEMF may be an effective and safe modality for the treatment of chronic low back pain disorders. More studies are needed to test this hypothesis.

Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy.

Postherpetic neuralgia (PHN) is a debilitating chronic pain condition, yet there is a lack of knowledge regarding underlying brain activity. Here we identify brain regions involved in spontaneous pain of PHN (n=11) and determine its modulation with Lidoderm therapy (patches of 5% lidocaine applied to the PHN affected body part). Continuous ratings of fluctuations of spontaneous pain during fMRI were contrasted to ratings of fluctuations of a bar observed during scanning, at three sessions: (1) pre-treatment baseline, (2) after 6h of Lidoderm treatment, and (3) after 2 weeks of Lidoderm use. Overall brain activity for spontaneous pain of PHN involved affective and sensory-discriminative areas: thalamus, primary and secondary somatosensory, insula and anterior cingulate cortices, as well as areas involved in emotion, hedonics, reward, and punishment: ventral striatum, amygdala, orbital frontal cortex, and ventral tegmental area. Generally, these activations decreased at sessions 2 and 3, except right anterior insular activity which increased with treatment. The sensory and affective activations only responded to the short-term treatment (6h of Lidoderm); while the ventral striatum and amygdala (reward-related regions) decreased mainly with longer-term treatment (2 weeks of Lidoderm). Pain properties: average magnitude of spontaneous pain, and responses on Neuropathic Pain Scale (NPS), decreased with treatment. The ventral striatal and amygdala activity best reflected changes in NPS, which was modulated only with longer-term treatment. The results show a specific brain activity pattern for PHN spontaneous pain, and implicate areas involved in emotions and reward as best reflecting changes in pain with treatment.

Cognitive factors influence outcome following multidisciplinary chronic pain treatment: a replication and extension of a cross-lagged panel analysis.

Reducing maladaptive cognitions is hypothesized to constitute an active therapeutic process in multidisciplinary pain programs featuring cognitive-behavioral interventions. A cross-lagged panel design was used to determine whether: a) early-treatment cognitive changes predicted late-treatment pain, interference, activity and mood changes, but not vice versa; b) three cognitive factors made unique contributions to outcome; c) substantial cognitive changes preceded substantial improvements in outcome. Sixty-five chronic pain patients, participating in a 4-week multidisciplinary program, completed measures of pain helplessness, catastrophizing, pain-related anxiety (process factors), pain severity, interference, activity level and depression (outcomes) at pre-, mid- and posttreatment. Results showed that early-treatment reductions in pain helplessness predicted late-treatment decreases in pain and interference, but not vice versa, and that early-treatment reductions in catastrophizing and pain-related anxiety predicted late-treatment improvements in pain severity, but not vice versa. Findings suggested that the three process factors predicted improvements mostly in common. However, little evidence was found that large early-treatment reductions in process variables preceded extensive improvements in pain. Findings replicate those of a recent report regarding cross-lagged effects, and offer support that cognitive changes may indeed influence late-treatment changes in outcomes.

Nicotine and caffeine intake in complex regional pain syndrome.

UNLABELLED: {\it OBJECTIVE: } Nicotine and caffeine are vasoconstrictors. Complex regional pain syndrome (CRPS) is defined to involve disproportionate pain and autonomic dysfunction [1]. The objectives of this study were to identify the prevalence of smoking and caffeine intake in CRPS, to explore the relationship of pain intensity with smoking and caffeine consumption, and to explore the relationship of pain intensity, anxiety and disability among CRPS patients who smoke, use caffeine, or both. {\it DESIGN: } One hundred eleven patients, with CRPS type I or II, from two academic rehabilitation pain clinics were reviewed. Data were collected retrospectively by reviewing CRPS patients' self-reported pain level using visual analogue scales (VAS), Beck Depression Inventory (BDI), Pain Disability Index (PDI), and Pain Anxiety Symptoms Scale (PASS). Status of daily smoking and caffeine consumption were also recorded. {\it RESULTS: } Smoking prevalence among CRPS was significant higher than the national average (p < 0.001). There were no significant relationships between the perceived pain level and either daily smoking, daily caffeine intake, or both (p > 0.430). In patients with CRPS I higher PASS scores were positively associated with dichotomous use of smoking and caffeine (p < 0.05). The PASS scores among patients with CRPS~II were not available for analysis. {\it CONCLUSIONS: } The smoking prevalence was higher than the national average among patients with CRPS I and II. Among patients with CRPS~I smoking and caffeine consumption were greater in those who reported more pain-related anxiety, but did not influence pain intensity. The clinical implications of these findings will be discussed.

A fourth empirically derived cluster of chronic pain patients based on the multidimensional pain inventory: evidence for repression within the dysfunctional group.

The authors proposed that chronic pain patients with repressive defenses are not represented in current 3-cluster solutions of the Multidimensional Pain Inventory (MPI; R. D. Kerns, D. C. Turk, & T. E. Rudy, 1985) and that such a group can be distinguished by using a measure of defensiveness together with subscales of the MPI. They expected these patients to be described both by high defensiveness and by elevated pain and disability but minimal emotional distress. For 178 pain patients, hierarchical cluster analyses were performed on the MPI and Balanced Inventory of Desirable Responding (D. L. Paulhus, 1984). A 3-cluster solution replicated past findings in identifying dysfunctional, interpersonally distressed, and adaptive coper groups. A 4-cluster solution fit the data better, with a repressor group described by high pain, low activity and low distress emerging from the dysfunctional group. Profile analysis of validation measures showed that repressors scored comparably with dysfunctional patients on somatic symptoms of depression, pain severity, and perceived disability but significantly higher on these factors than the adaptive copers. Repressors scored comparably with adaptive copers on cognitive-affective symptoms of depression, anxiety, and anger but significantly lower on these variables than dysfunctional patients. Repressors also reported greater pain severity and perceived disability relative to their reports of negative affect, whereas dysfunctional and adaptive coper groups exhibited no such disparities. Without a measure of defensiveness, the MPI may misclassify a distinct group of patients as dysfunctional, but who readily endorse physical symptoms yet report low levels of emotional distress.

Conducting clinical trials to establish drug efficacy in chronic pain.

Design of clinical trials to establish drug efficacy in chronic pain is a complicated issue, and numerous factors must be considered in identifying an optimal study design. Investigators should begin by identifying a focused and testable research question, with the outcome variables operationalized in a way that allows appropriate quantitative analysis. The prospective, randomized, placebo-controlled, doubled-blind study using validated quantitative measures is considered the optimal clinical trial design. Within this general study type, the between-subjects design has less statistical power than does the crossover design, in which the patient serves as his or her own control. However, potential problems with the drug effects from the first condition carrying over into, and confounding, the second drug condition present a noteworthy limitation that must be addressed through adequate washout periods and statistical control if crossover designs are used. Retrospective designs may be useful primarily to take advantage of samples of convenience for development of pilot data that provide the basis for conducting better-controlled prospective studies. Sample selection issues must be considered during study design, including the sample size required (based on statistical power analysis), appropriate inclusion and exclusion criteria, and likely availability of qualifying patients. There are numerous statistical options for analyzing data that must be selected based on whether data are parametric or nonparametric, whether within-subject (crossover) or between-subject comparisons are used, and whether baseline values of outcome measures affect the degree of change in these measures over the course of the study. Involvement of a biostatistical consultant is recommended during all phases of clinical trials.

A clinical approach to complex regional pain syndrome.

The clinical approach to complex regional pain syndrome (CRPS) is complicated by a lack of precision diagnostically, and a lack of evidence-based information for treatment. The vagaries of diagnosis were somewhat improved by the Orlando Conference (1993), where a consensus panel of experts developed a new taxonomy and criteria. Unfortunately the criteria can be based entirely on subjective grounds (patient history), and as such provides a very sensitive but not very specific device. There is some effort in the research community to amend these criteria to make them more specific. We encourage the practicing physician to include as much objective data along with the quasi-objective and subjective information currently used in formulating the diagnosis. This imprecision in diagnostic issues has significantly hampered treatment because it has not led to solid, generalizable, randomized controlled trials. To date there are no substantial scientific trials of any particular therapy or medication in the specific diagnosis of CRPS. Much can be inferred from the work with peripheral neuropathy and central pain. However, it is unlikely that this will be a perfect concordance with best therapy for CRPS. It remains our responsibility to diagnose each patient as best we can, supported by the best possible objective signs and testing. Once the diagnosis is made it is necessary to proceed in a pragmatic empirical way, following the best guidelines available. The guidelines should be considered a "rough sketch" and the key to clinical success will be flexibility, a vast fund of the available knowledge, patience, and compassion. To allow the deficiencies in the science to paralyze the clinical process is therapeutic nihilism, and not acceptable.

Signs and symptoms of the myofascial pain syndrome: a national survey of pain management providers.

OBJECTIVE: The goal of this study was to assess clinical consensus regarding whether myofascial pain syndrome (MPS) is a legitimate and distinct diagnosis as well as the signs and symptoms characterizing MPS. DESIGN: A standardized mailed survey with return postage provided. SUBJECTS: A total of 1,663 American Pain Society members in medically related disciplines listed in the 1996/1997 directory. OUTCOME MEASURES: A standardized survey assessing clinical opinion regarding whether MPS is a legitimate diagnosis, whether MPS is a clinical entity distinct from fibromyalgia, and the signs and symptoms believed to be "essential to," "associated with," or "irrelevant to" to the diagnosis of MPS. RESULTS: Of the 403 surveys returned, 88.5% respondents reported that MPS was a legitimate diagnosis, with 81% describing MPS as distinct from fibromyalgia. The only signs and symptoms described as essential to the diagnosis of MPS by greater than 50% of the sample were regional location, presence of trigger points, and a normal neurologic examination. Regarding the signs and symptoms considered to be essential or associated with MPS, more than 80% of respondents agreed on regional location, trigger points, normal neurologic examination, reduced pain with local anesthetic or "spray and stretch," taut bands, tender points, palpable nodules, muscle ropiness, decreased range of motion, pain exacerbated by stress, and regional pain described as "dull," "achy," or "deep." Sensory or reflex abnormalities, scar tissue, and most test results were considered to be irrelevant to the diagnosis of MPS by a large proportion of the respondents. CONCLUSIONS: There was general agreement across specialties that MPS is a legitimate diagnosis distinct from fibromyalgia. There was a high level of agreement regarding the signs and symptoms essential or associated with a diagnosis of MPS. Differences across specialties are discussed. This survey provides a first step toward the development of consensus-based diagnostic criteria for MPS, which can then be validated empirically.

A review of three commonly prescribed skeletal muscle relaxants.

Skeletal muscle relaxants (SMR) are commonly used drugs prescribed for the treatment of muscle spasm and discomfort. Although many have been in use for decades, physicians may be unaware of the accumulating evidence of their risks, benefits, safety and side effects. This review examines the efficacy, side effects, and safety of three commonly prescribed SMRs: metaxalone, cyclobenzaprine, and carisoprodol. All three appear to have equal efficacy, but their side effects vary considerably. Metaxalone has the fewest reports of side effects, and no reports of major safety issues. Cyclobenzaprine, closely related to the tricyclic antidepressants, causes the expected lethargy and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances. Carisoprodol raises the greatest concern. Reports in the literature suggest a significant potential for physical and psychological dependence perhaps suggesting a potential for misuse. It also has, perhaps, the greatest toxicity. A secondary goal of this review is to stimulate more discourse about these commonly used, but poorly understood compounds.

Theoretical review: altered pain regulatory systems in chronic pain.

This review synthesizes the existing literature regarding the relationship between resting blood pressure and pain sensitivity, and the literature indicating possible endogenous opioid dysfunction in chronic pain. Adaptive interactions between the cardiovascular and pain regulatory systems occur in healthy individuals, with greater blood pressure associated with decreased acute pain sensitivity. Endogenous opioids appear necessary for full expression of this relationship. There is ample evidence indicating diminished endogenous opioid CSF/plasma levels in chronic pain patients, yet little is known about the functional effects of these opioid changes. A theoretical model is proposed based upon the literature reviewed suggesting progressive dysfunction in endogenous opioid systems with increasing chronic pain duration. This dysfunction is hypothesized to result in dysregulation of normally adaptive relationships between the cardiovascular and pain regulatory systems, resulting in increased chronic pain intensity and increased acute pain sensitivity among chronic pain patients. Preliminary data are consistent with the hypothesis of progressive opioid changes resulting in dysfunctional alterations in the adaptive blood pressure-pain relationship. Clinical implications of this theory are discussed.

Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive?

This is a multisite study examining the internal validity and comprehensiveness of the International Association for the Study of Pain (IASP) diagnostic criteria for Complex Regional Pain Syndrome (CRPS). A standardized sign/symptom checklist was used in patient evaluations to obtain data on CRPS-related signs and symptoms in a series of 123 patients meeting IASP criteria for CRPS. Principal components factor analysis (PCA) was used to detect statistical groupings of signs/symptoms (factors). CRPS signs and symptoms grouped together statistically in a manner somewhat different than in current IASP/CRPS criteria. As in current criteria, a separate pain/sensation criterion was supported. However, unlike in current criteria, PCA indicated that vasomotor symptoms form a factor distinct from a sudomotor/edema factor. Changes in range of motion, motor dysfunction, and trophic changes, which are not included in the IASP criteria, formed a distinct fourth factor. Scores on the pain/sensation factor correlated positively with pain duration (P<0. 001), but there was a negative correlation between the sudomotor/edema factor scores and pain duration (P<0.05). The motor/trophic factor predicted positive responses to sympathetic block (P<0.05). These results suggest that the internal validity of the IASP/CRPS criteria could be improved by separating vasomotor signs/symptoms (e.g. temperature and skin color asymmetry) from those reflecting sudomotor dysfunction (e.g. sweating changes) and edema. Results also indicate motor and trophic changes may be an important and distinct component of CRPS which is not currently incorporated in the IASP criteria. An experimental revision of CRPS diagnostic criteria for research purposes is proposed. Implications for diagnostic sensitivity and specificity are discussed.

External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain.

Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.

Gabapentin: a new tool in the treatment of neuropathic pain.

Human neuropathic pain remains a prevalent and pervasive problem in our society. Pharmacologically there is also no single, uniformly well-tolerated drug that is reliably helpful. Gabapentin has emerged as a useful new tool based on the results of two large multicenter trials in models of human neuropathy. Gabapentin proved to be a significantly better analgesic than placebo, was well tolerated in the elderly population, and had a significant positive impact on several subjective and objective outcome measures. A discussion of the standard treatments and the studies supporting this new tool is the purpose of this review.

New developments in rehabilitation of neuropathic pain syndromes.

The common medical treatments of neuropathic pain, medication and nerve blocks, are often only partially effective in providing significant and long-term pain relief. Patients suffering chronic pain often fall prey to associated emotional suffering, functional impairment, and difficulties in multiple areas of their lives, including family disruption, social withdrawal, and vocational disability. An interdisciplinary approach to pain management draws on the skills of physical and occupational therapists, pain psychologists, biofeedback specialists, and vocational counselors. It focuses on both pain management and functional restoration, and should be considered standard treatment for chronically painful conditions. Interdisciplinary pain management views the patient as an active agent, responsible for learning and applying self-management techniques for controlling pain, with the staff assuming a teaching and consulting role. Although much more labor intensive, interdisciplinary pain management is more effective over time in managing chronic pain, in preventing unnecessary emotional and physical impairment, and in controlling overall medical costs.

IASP diagnostic criteria for complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain.

OBJECTIVE: To assess the ability of the International Association for the Study of Pain Complex Regional Pain Syndrome (CRPS) diagnostic criteria and associated features to discriminate between CRPS patients and patients with painful diabetic neuropathy. DESIGN: Prospective assessment of signs and symptoms in a series of CRPS and diabetic neuropathy patients. SETTING: University of Washington Multidisciplinary Pain Center. PATIENTS: A consecutive series of 18 CRPS patients and 30 diabetic neuropathy patients. INTERVENTIONS: Patients completed a 10-item patient history questionnaire assessing symptoms of CRPS prior to medical evaluation. The evaluating physician completed a 10-item patient examination questionnaire assessing objective signs of CRPS. OUTCOME MEASURES: The analyses conducted were designed to test the ability of CRPS signs and symptoms and associated features to discriminate between CRPS patients and diabetic neuropathy patients. RESULTS: Data analysis suggested that CRPS decision rules may lead to overdiagnosis of the disorder. Diagnosis based on self-reported symptoms can be diagnostically useful in some circumstances. The addition of trophic tissue changes, range of motion changes, and "burning" quality of pain did not improve diagnostic accuracy, but the addition of motor neglect signs did. Test of a CRPS scoring system resulted in improved accuracy relative to current criteria and decision rules. CONCLUSIONS: Poorly understood disorders lacking prototypical signs/symptoms and diagnostic laboratory testing must rely on the development of reliable diagnostic guidelines. The results of this study should assist in the further refinement of the CRPS diagnostic criteria.

Controlled trial of ketorolac in tension-type headache.

Intramuscular ketorolac 60 mg, meperidine 50 mg plus promethazine 25 mg, and normal saline were compared in acute exacerbations of tension-type headache. Forty-one subjects (30 females and 11 males) were randomized into three groups and evaluated by the McGill Short-Form Pain Questionnaire before treatment, and 0.5, 1, 2, 3, 4, 5, and 6 hours after treatment. All three groups showed a significant treatment effect that persisted for the 6 hours of evaluation. Ketorolac treatment was significantly better than placebo at 0.5 and 1 hour by the Visual Analog Scale (VAS) and Pain Rating Index, and better than meperidine at 2 hours (by the VAS). Meperidine and placebo did not differ at any time point. Ketorolac is effective in short-term treatment of tension-type headache.