Pain medicine training resources: Module 8

Abstract
The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61-70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway.

Abstract
Objective: Factors influencing disability and work absence in complex regional pain syndrome type-1 (CRPS)-1 have not been thoroughly described in the literature. We sought to determine whether demographic variables, work-related factors, CRPS clinical severity ratings, pain scores, or psychological variables were associated with disability and sick leave in early CRPS-1.

Methods: A total of 66 CRPS-1 patients were recruited within 12 weeks of CRPS onset. Patients completed measures of pain, depression, anxiety, stress, pain catastrophizing, and pain-related fear. A physical examination was conducted to assess signs and symptoms of CRPS and to calculate a CRPS severity score. Demographic details, clinical details, treatments, work type, and work status were recorded.

Results: In multivariate analyses, the following factors were associated with greater disability: higher pain scores, more restricted ankle or wrist extension, and higher levels of depression. Among the 49 who were either working or studying before developing CRPS, 28 had stopped work or study at the time of assessment. Multivariate analyses showed that sick leave was more likely among those whose CRPS was triggered by more severe injuries, whose work was more physically demanding, among those with higher disability scores, and there was also a significant effect of depression on sick leave, which was mediated by disability.

Discussion: Although the study was cross-sectional and so cannot differentiate cause from effect, results suggest that even in the early stages of CRPS, a cycle of pain, disability, depression, and work absence can emerge. Treatments aimed to prevent this cycle may help prevent adverse long-term outcomes.

Abstract
Psychological and behavioral factors can exacerbate the pain and dysfunction associated with complex regional pain syndrome (CRPS) and could help maintain the condition in some patients. Effective management of CRPS requires that these psychosocial and behavioral aspects be addressed as part of an integrated multidisciplinary treatment approach. Well-controlled studies to guide the development of a psychological approach to CRPS management are not currently available. A sequenced protocol for psychological care in CRPS is therefore proposed based on available data and clinical experience. Regardless of the duration of the condition, all CRPS patients and their families should receive education about the negative effects of disuse, the pathophysiology of the syndrome, and possible interactions with psychological/behavioral factors. Patients with acute CRPS (<6-8 weeks) may not need additional psychological care. All patients with chronic CRPS should receive a thorough psychological evaluation, followed by cognitive-behavioral pain management treatment, including relaxation training with biofeedback. Patients making insufficient overall treatment progress or in whom comorbid psychiatric disorders/major ongoing life stressors are identified should additionally receive general cognitive-behavioral therapy to address these issues. The psychological component of treatment can work synergistically with medical and physical/occupational therapies to improve function and increase patients' ability to manage the condition successfully.

Abstract
Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features. Few treatments have proven effective, in part, because of a historically poor understanding of the mechanisms underlying the disorder. CRPS research largely conducted during the past decade has substantially increased knowledge regarding its pathophysiologic mechanisms, indicating that they are multifactorial. Both peripheral and central nervous system mechanisms are involved. These include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. Relative contributions of the mechanisms underlying CRPS may differ across patients and even within a patient over time, particularly in the transition from "warm CRPS" (acute) to "cold CRPS" (chronic). Enhanced knowledge regarding the pathophysiology of CRPS increases the possibility of eventually achieving the goal of mechanism-based CRPS diagnosis and treatment.

Abstract
Numerous studies have shown that pain-related fear is one of the strongest predictors of pain disability in patients with chronic musculoskeletal pain, and there is evidence that the reduction of pain-related fear through an exposure treatment can be associated with restoration of functional abilities in patients with complex regional pain syndrome type I (CRPS-I). These findings suggest that pain-related fear may be associated with functional limitations in neuropathic pain as well. The aim of the current study was to test whether the debilitating role of pain-related fear generalizes to patients with CRPS-I. The results of 2 studies are presented. Study I includes a sample of patients with early CRPS-I referred to an outpatient pain clinic. In Study II, patients with chronic CRPS who are members of a patients' association were invited to participate. The results show that in early CRPS-I, pain severity but not fear of movement/(re)injury as measured with the Tampa Scale for Kinesiophobia was related to functional limitations. In patients with chronic CRPS-I, however, perceived harmfulness of activities as measured with the pictorial assessment method significantly predicted functional limitations beyond and above the contribution of pain severity. Not fear of movement/(re)injury in general, but the perceived harmfulness of activities appears a key factor that might be addressed more systematically in the clinical assessment of patients with CRPS-I. These results support the idea that pain-related fear might be a promising concept in the understanding of pain disability in patients with neuropathic pain.

Perspective: This is the first study showing that perceived harmfulness of activities contribute to the functional limitations in CRPS-I. The current findings may help clinicians customizing cognitive-behavioral treatments for patients with chronic neuropathic pain.

Abstract
Dysfunction in the central nervous system is thought to underlie the movement disorders that commonly occur in complex regional pain syndrome (CRPS), with much of the literature focusing on reorganization of the primary motor cortex (M1). Presumed changes in the M1 representation of the CRPS-affected body part have contributed to new CRPS treatments, which are increasingly being integrated in the clinic. We systematically investigated the evidence for altered M1 function in CRPS. We adhered to rigorous systematic review procedure in our search strategy, risk-of-bias appraisal, and data extraction. Eighteen studies comprising 14 unique data sets were included. The included studies used several neuroimaging techniques, whose outcomes we grouped into M1 cortical excitability, spatial representation, reactivity, and glucose metabolism, and conducted meta-analyses where possible. Risk of bias across studies was high, mainly due to missing data and unblinded assessment of outcomes. No definitive conclusions can be drawn regarding M1 spatial representation, reactivity, or glucose metabolism in CRPS. There is limited evidence for bilateral M1 disinhibition in CRPS of the upper limb.

Perspective: Despite widely held assumptions of primary motor cortex dysfunction in complex regional pain syndrome, there is only evidence to support bilateral disinhibition, and there is high risk of bias across the literature.

Abstract
Purpose: Although multiple treatments have been advocated for complex regional pain syndrome (CRPS), the levels of supportive evidence are variable and sometimes limited. The purpose of this updated review is to provide a critical analysis of the evidence pertaining to the treatment of CRPS derived from recent randomized-controlled trials (RCTs).

Source: The MEDLINE, EMBASE, Psychinfo, and CINAHL databases were searched to identify relevant RCTs conducted on human subjects and published in English between 1 May 2009 and 24 August 2017.

Principal findings: The search yielded 35 RCTs of variable quality pertaining to the treatment of CRPS. Published trials continue to support the use of bisphosphonates and short courses of oral steroids in the setting of CRPS. Although emerging evidence suggests a therapeutic role for ketamine, memantine, intravenous immunoglobulin, epidural clonidine, intrathecal clonidine/baclofen/adenosine, aerobic exercise, mirror therapy, virtual body swapping, and dorsal root ganglion stimulation, further confirmatory RCTs are warranted. Similarly, trials also suggest an expanding role for peripheral sympathetic blockade (i.e., lumbar/thoracic sympathetic, stellate ganglion, and brachial plexus blocks).

Conclusions: Since our prior systematic review article (published in 2010), 35 RCTs related to CRPS have been reported. Nevertheless, the quality of trials remains variable. Therefore, further research is required to continue investigating possible treatments for CRPS.

Abstract
A series of developments in relation to the accountability of expert witnesses and the admissibility of their opinions is taking place. This extends to encroachments in the United Kingdom on expert witness immunity, the imposition of disciplinary liability for registered health practitioners in Australia and the United Kingdom, and recommendations from the United Kingdom Law Commission for a systematised procedure for reliability determination as a prerequisite for admissibility rulings. This combination of measures is indicative of international concern about the contemporary role of expert witnesses. It highlights the need for both empirical information about whether the anecdotal and experiential concerns about expert evidence are well-founded and for the provision of better and clearer guidance to experts and litigators alike about the underpinnings and methodologies that are permissible for admissible and probative expert opinions.

Abstract
Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the "Budapest Criteria") regarding diagnostic accuracy. Structured evaluations of CRPS-related signs and symptoms were conducted in 113 CRPS-I and 47 non-CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.

Abstract
Objective: This is the fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy).

Methods: Expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included. The literature review was supplemented with knowledge gained from extensive empirical clinical experience, particularly in areas where high-quality evidence to guide therapy is lacking.

Results: The research quality, clinical relevance, and "state of the art" of diagnostic criteria or treatment modalities are discussed, sometimes in considerable detail with an eye to the expert practitioner in each therapeutic area. Levels of evidence are mentioned when available, so that the practitioner can better assess and analyze the modality under discussion, and if desired, to personally consider the citations. Tables provide details on characteristics of studies in different subject domains described in the literature.

Conclusions: In the humanitarian spirit of making the most of all current thinking in the area, balanced by a careful case-by-case analysis of the risk/cost vs benefit analysis, the authors offer these "practical" guidelines.

Abstract
Introduction: Complex regional pain syndromes (CRPS) are rare painful conditions characterized by considerable variability in possible triggering factors, usually traumatic, and in the clinical scenario. The limited knowledge of the pathophysiological mechanisms has led to countless treatment attempts with multiple conservative and surgical options that act by different mechanisms of action.

Areas covered: In this narrative review, the authors discuss key points about CRPS definitions, diagnostic criteria and pitfalls, pathophysiological hypotheses, and treatment strategies with particular reference to pharmacotherapy. The article was based on a literature search using PubMed while the available guidelines for the management of CRPS were also examined.

Expert opinion: According to the quality of evidence, pharmacological interventions for CRPS seem to be more effective all the more so when they act on peripheral mechanisms, particularly on nociceptive pain, and when applied early in the disease, while reliable evidence about central mechanisms of chronic pain in CRPS is lacking. In our opinion, drug therapy should be preferred as early as possible, particularly in warm forms of CRPS to prevent significant functional limitation, psychological distress, and social and economic fallout.

Abstract
Background: There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery (GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome (CRPS). However, whether GMI is effective in clinical practice is not established.

Aim: To establish whether GMI is effective in clinical practice.

Methods: We undertook a prospective audit of GMI treatment at two UK centres with a special interest in the management of patients with CRPS. All patients received GMI, in conjunction with a range of other 'best practice' physical and psychological interventions.

Results: The patients' average pain intensities did not improve with treatment [centre 1: n = 20, pre-post numeric rating scale (NRS) difference 0.6 [confidence interval (CI) -0.3 to 1.5]; centre 2: n = 12, pre-post NRS difference 0.2 (CI: -0.9 to 1.2)]. Patients at centre 1 reported significant functional improvement. Improved performance on left/right judgement replicated in both centres seen in the clinical trials.

Conclusions: The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice.

Abstract
Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo- and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold-type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation-induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism-based treatment and improve clinical outcome.

Abstract
Background: Complex regional pain syndrome (CRPS) I is a debilitating neuropathic pain disorder characterized by burning pain and allodynia. Spinal cord stimulation (SCS) is effective in the treatment of CRPS I in the medium term but its long-term efficacy and ability to improve functional status remains controversial.

Objective: To evaluate the ability of SCS to improve pain, functional status, and quality of life in the long term.

Methods: We retrospectively analyzed 25 patients over a mean follow-up period of 88 months. The parameters for evaluation were visual analog scale (VAS), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), EuroQoL-5D (EQ-5D) and Short Form 36 (SF-36), and drug consumption. Evaluations were conducted at point of entry, 3 months, 12 months, and last follow-up at 88 months (mean).

Results: At baseline, the mean scores were VAS 8.4, ODI 70%, BDI 28, EQ-5D 0.30, and SF-36 24. In general, maximum improvement was recorded at follow-up at 3 months (VAS 4.8, ODI 45%, BDI 15, EQ-5D 0.57, and SF-36 45). At last follow-up, scores were 5.6, 50%, 19, 0.57, and 40, respectively. Despite some regression, at last follow-up benefits were maintained and found to be statistically significant (P < .001) compared with baseline. Medication usage declined. SCS did not prevent disease spread to other limbs. Best results were achieved in stage I CRPS I, patients under 40 years of age, and those receiving SCS within 1 year of disease onset.

Conclusion: SCS improves pain, quality of life, and functional status over the long term and consequently merits early consideration in the treatment continuum.

Abstract
Complex regional pain syndrome (CRPS) is a disabling pain condition poorly understood by medical professionals. Because CRPS is particularly enigmatic, and has significant impact on patient function, researchers have examined psychological processes present among patients with this diagnosis. This systematic review examines psychosocial factors associated with CRPS, both predictors and sequelae. Our conclusions are that CRPS is associated with negative outcomes, both psychological (e.g., increased depression and anxiety) and psychosocial (e.g., reduced quality of life, impaired occupational function) in nature. However, research does not reveal support for specific personality or psychopathology predictors of the condition.

Abstract
A complex regional pain syndrome (CRPS)--multiple system dysfunction, severe and often chronic pain, and disability--can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.

Abstract
This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called "chronic secondary pain" where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.

Abstract
Objectives: We conducted a systematic review of the literature with meta-analysis to determine whether complex regional pain syndrome (CRPS) is associated with a specific inflammatory profile and whether this is dependent on the duration of the condition.

Methods: Comprehensive searches of the literature using MEDLINE, Embase, Scopus, Web of Science, and reference lists from published reviews identified articles that measured inflammatory factors in CRPS. Two independent investigators screened titles and abstracts, and performed data extraction and risk of bias assessments. Studies were subgrouped by medium (blood, blister fluid, and CSF) and duration (acute and chronic CRPS). Where possible, meta-analyses of inflammatory factor concentrations were performed and pooled effect sizes were calculated using random-effects models.

Results: Twenty-two studies were included in the systematic review and 15 in the meta-analysis. In acute CRPS, the concentrations of interleukin (IL)-8 and soluble tumor necrosis factor receptors I (sTNF-RI) and II (sTNF-RII) were significantly increased in blood. In chronic CRPS, significant increases were found in 1) TNFα, bradykinin, sIL-1RI, IL-1Ra, IL-2, sIL-2Ra, IL-4, IL-7, interferon-γ, monocyte chemoattractant protein-1 (MCP-1), and sRAGE (soluble receptor for advanced glycation end products) in blood; 2) IL-1Ra, MCP-1, MIP-1β, and IL-6 in blister fluid; and 3) IL-1β and IL-6 in CSF. Chronic CRPS was also associated with significantly decreased 1) substance P, sE-selectin, sL-selectin, sP-selectin, and sGP130 in blood; and 2) soluble intercellular adhesion molecule-1 (sICAM-1) in CSF. Most studies failed to meet 3 or more of our quality criteria.

Conclusion: CRPS is associated with the presence of a proinflammatory state in the blood, blister fluid, and CSF. Different inflammatory profiles were found for acute and chronic cases.

Abstract
Background: Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I.

Method: A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment.

Results: For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I.

Conclusions: Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines.

Abstract
Forensic psychiatric reports are often the final product of a psychiatrist's work in a particular case because most cases do not go to trial but instead are settled through negotiation or plea bargaining. This article addresses the planning, writing, and editing of forensic reports. Planning a report requires thorough data gathering, and thoughtful organization of the report into specific subheadings. Throughout the report there should be a clear separation of factual data from professional opinions. Ten pitfalls of report writing are identified. The most important part of the forensic report is the opinion section. The evidence for the opinion should begin with the strongest points and the reasons supporting the opinion should be completely explained. Finally, ethical issues are addressed.

Abstract
Background: Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known.

Objectives: To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II.

Search methods: We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress.

Selection criteria: We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist-administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability.

Data collection and analysis: Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed 'Risk of bias' assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at 'high' risk of bias (15 trials) and the remainder were at 'unclear' risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach.We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) -21.00, 95% CI -31.17 to -10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving 'impairment' at long-term (12 month) follow-up compared to a minimal 'social work' intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI -4.71 to -2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD -2.3, 95% CI -2.88 to -1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror).There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-term in people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I.Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review.

Authors' conclusions: The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered.

Abstract
Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.