Case report: Dorsal root ganglion stimulator lead fracture.

BACKGROUND: One of the unique advances in neuromodulation for chronic pain has been spinal cord stimulators (SCS) and dorsal root ganglion stimulators (DRG-S). These devices have aided in conditions such as neuropathic pain, complex regional pain syndromes, failed back surgery, and peripheral neuropathies. With these benefits, however, complications from implantable stimulators have included lead fractures and migration. The authors reviewed a lead migration, kinking, and subsequent fracture event involving a patient with complex regional pain syndrome (CRPS) II, who was treated with a DRG-S. CASE PRESENTATION: The case report follows this patient, from their past medical history to assessment of appropriate qualifications for neuromodulation, to successful surgical placement, to follow-up care. The authors further monitored assessment of inefficacy of pain relief, and identification of lead migration and kinking through imaging. In the process of removal, due to lead stress, lead fracturing occurred. After lead removal, the leads were fully replaced, and the patient was followed up and experienced improved pain relief. CONCLUSION: The case report assesses probable mechanisms of lead fracture and considerations for physicians for future assessment and triage of neuromodulation efficacy.

[Complex regional pain syndrome]. / Syndrome douloureux régional complexe.

Complex regional pain syndrome is a clinical entity that usually occurs following trauma, surgery, or other triggering event. Patients complain of pain described as burning, associated with sensory, vasomotor, sudomotor, motor and/or trophic disorders. The pain appears disproportionate to the initial lesion. The diagnosis is purely clinical and based on the Budapest criteria. It is a diagnosis of exclusion. The pathophysiology is still poorly understood and is thought to be multifactorial. Several mechanisms have been described: an inflammatory state, an overactivation of the sympathetic autonomic nervous system and a poor perception of pain at the central level. The management of signs and symptoms is therefore global. It involves physiotherapy and occupational therapy, often combined with analgesic medications. Psychological treatment may be proposed in certain circumstances. The natural evolution is rather favourable.

Le syndrome douloureux régional complexe constitue une entité clinique survenant habituellement suite à un traumatisme, une chirurgie ou un autre événement déclencheur. Les patients se plaignent d'une douleur décrite comme une brûlure, associée à des troubles sensoriels, vasomoteurs, sudomoteurs, moteurs et/ou trophiques. La douleur apparaît disproportionnée par rapport à la lésion initiale. Le diagnostic est purement clinique et repose sur les critères de Budapest. Il s'agit d'un diagnostic d'exclusion. La physiopathologie est encore peu connue, et serait multifactorielle. Plusieurs mécanismes sont décrits : un état inflammatoire, une suractivation du système nerveux autonome sympathique et une mauvaise perception de la douleur au niveau central. La prise en charge des signes et symptômes est donc globale. Elle fait intervenir une rééducation en kinésithérapie et ergothérapie, souvent associée à un traitement antalgique médicamenteux. Une prise en charge en psychologie peut être proposée dans certaines circonstances. L'évolution naturelle est plutôt favorable.

Incidence and risk factors for complex regional pain syndrome in radius fractures: meta-analysis.

PURPOSE: This meta-analysis aimed to evaluate the incidence and risk factors for complex regional pain syndrome (CRPS) in radius fractures. METHODS: The meta-analysis was performed using the PubMed, Embase, Scopus, and Cochrane Collaboration Library databases. Studies focusing on patients with conservative or surgically treated radius fractures leading to CRPS were included. A control group consisting of patients with radius fractures and no CRPS (-) was included. The outcome measures were incidence and risk factors. Comparative studies were also included. Data were combined using Review Manager 5.4. RESULTS: Out of 610 studies, nine studies were included. The incidence of CRPS after radius fractures ranged from 0.19 to 13.63% (95% CI: 11.12-16.15%). Open fractures, high-energy mechanisms in radial head fractures, and associations with ulnar fractures were risk factors for CRPS [(RR: 0.98; 95% CI: 0.97-1.00), (RR: 0.18; 95% CI: 0.07-0.47), and (RR: 1.25; 95% CI: 1.17-1.35), respectively]. Other risk factors were female sex and high body mass index [(RR: 1.20; 95% CI: 1.05-1.37) and (MD: 1.17; 95% CI: 0.45-1.88)]. Psychiatric factors also increased the incidence of CRPS (RR: 2.04; 95% CI: 1.83-2.28). On the other hand, the type of surgery (external fixation or open reduction and internal fixation) and manipulations; associated comorbidities (diabetes and hypertension) together with tobacco and alcohol abuse; marital status, educational level, employment status, and socioeconomic status were not risk factors (p > 0.05). CONCLUSION: The incidence of CRPS in radius fractures was 13.63%. Fractures with greater complexity or greater associated tissue damage, female sex, high BMI, and psychiatric disorders were risk factors for the development of CRPS. LEVEL OF EVIDENCE: Meta-analysis of cohort and case series studies; II.

Latent infection after spinal cord stimulation device implantation for complex regional pain syndrome: A case report.

RATIONALE: Spinal cord stimulation (SCS) is one of the invasive treatments of complex regional pain syndrome (CRPS). The positive effect has been observed for several years after implantation. However, infection is a common cause of SCS failure and device removal. PATIENT CONCERNS: Here we describe a case of latent infection at the implantable generator pocket site 9 years after SCS implantation in a patient with CRPS. DIAGNOSES: A 52-year-old patient was diagnosed with type 1 CRPS. The right foot pain was intractable with standard treatments. SCS implantation was performed and SCS worked well without complication. Nine years later, the patient revisited due to pain, tenderness, and redness at the abdominal wall for 2 weeks. The right foot pain was maintained with NRS 4 for 8 years, and the stimulation stopped 1 year back. SCS infection was diagnosed. INTERVENTIONS: The patient underwent SCS removal surgery. OUTCOMES: All SCS devices were removed successfully. The patient was discharged without any complications. CONCLUSIONS: While uncommon, infection after SCS implantation can occur even 9 years later. Immediate diagnosis, proper antibiotics, and surgical removal could be needed to prevent further spread of infection and better prognosis.

Management of complex regional pain syndrome in trauma and orthopaedic surgery-a systematic review.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a neurological pain disorder that is challenging to diagnose and manage, resulting in increased morbidity and costs. It most commonly occurs following traumatic injury, such as a fracture, crush injury or surgery. Recent research has evaluated the efficacy of treatments which have contradicted previous hypotheses. This systematic review summarizes these findings to improve clinician's decision-making. SOURCES OF DATA: A comprehensive search of PubMed, MEDLINE and Embase databases from inception through January 2021 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened relevant articles discussing the management of CRPS in adult trauma patients. All prospective and retrospective studies, non-randomized comparison studies and case series were considered for inclusion. Data extraction was performed by populating a predefined data abstraction sheet. AREAS OF AGREEMENT: There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates, sympathectomy and brachial plexus blocks in the management of CRPS. AREAS OF CONTROVERSY: The latest evidence suggests that vitamin C has no significant role to play in the treatment or prevention of CRPS. GROWING POINTS: A multidisciplinary team approach and early diagnosis are imperative for successful treatment of CRPS. The Budapest criteria and the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines should be used when diagnosing CRPS. There is currently no clear evidence of superiority in any treatment. AREAS TIMELY FOR DEVELOPING RESEARCH: There are few high-quality studies that inform the best treatment modalities for CRPS. Though emerging treatments show promise, further research is needed.

Diagnosis and Outcomes of 225 Consecutive Cases of Complex Regional Pain Syndrome of the Hand.

BACKGROUND: The lack of specific tests and potential diagnostic inaccuracy may be behind the stunning figures of complex regional pain syndrome (CRPS) cases. The author tested the hypothesis that patients diagnosed with CRPS at referral could be assigned to recognized conditions and treated accordingly. METHODS: From January of 2018 to April of 2021, 225 consecutive patients attended the author's office having been diagnosed with and treated for CRPS for an average of 16 ± 26 months. There were 180 women and 45 men; no patient was excluded. RESULTS: All patients could be allocated in named conditions: 79 had a wrong diagnosis; seven had a true causalgia; 16 were dystonic-psychogenic hands; 20 presented a flare reaction; and 90 had an "irritative" carpal tunnel syndrome. The remaining 13 patients had a miscellany of symptoms within a substandard management setting. Surgery was offered to 175 with a correctable cause; 50 (20 of whom had a tangible cause responsible for their pain) declined, and their outcome is unknown. The remaining 125 were operated on and tracked for an average of 20 ± 9 months. In the operated group, pain dropped 7.5 ± 2.2 points ( P < 0.0001) on a numerical rating scale of 0 to 10. Disabilities of the Arm, Shoulder, and Hand questionnaire scores fell from 80 to 16 ( P < 0.0001). Patients who were operated on rated their satisfaction on a scale of 0 to 10 as 8.9 ± 1.9. CONCLUSIONS: Unlike with CRPS, all patients in this series had a true, diagnosable condition explaining their clinical picture. Most patients who agreed to be operated on had a favorable outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Comparison of Epidemiological Data of Complex Regional Pain Syndrome (CRPS) Patients in Relation to Disease Severity-A Retrospective Single-Center Study.

A retrospective data analysis of 159 complex regional pain syndrome (CRPS) patients (n = 116 women, 73.0%, mean age 60.9 ± 14.4 years; n = 43 men, 27.0%, mean age 52.3 ± 16.7 years) was performed from 2009 to 2020. The right side was affected in 74 patients (46.5%), the left in 84 patients (52.8%), and 1 patient (0.7%) developed a bilateral CRPS. Data were analyzed for the frequency and distribution of symptoms. The number of reduction maneuvers and the number of Budapest criteria were compared in relation to the severity of CRPS. Hand and wrist (n = 107, 67.3%), followed by foot and ankle (n = 36, 22.6%) and other locations (n = 16, 10.1%) were mainly affected by CRPS. The main causes included direct trauma (n = 120, 75.5%), surgery without previous trauma (n = 25, 15.7%), other causes (n = 9, 5.7%), and spontaneous development (n = 3, 1.9%); there was also missing documentation (n = 2, 1.3%). The most common symptoms were difference in temperature (n = 156, 98.1%), limitation of movement (n = 149, 93.7%), and swelling (n = 146, 91.8%). There was no correlation between the number of reduction maneuvers and the number of Budapest criteria. In summary, patients with the following constellation are at increased risk of CRPS: a female, over 60 years old, who has fallen and has sustained a fracture in the hand or wrist with persistent pain and has been immobilized with a cast for approx. 4 weeks.

Complex regional pain syndrome following vascular access creation for hemodialysis.

Pain and swelling of a limb following creation of arterio-venous fistula (AVF) are often attributable to vascular disorders like venous hypertension or limb ischaemia. Here we report the case of a 70-years old man who developed pain and swelling of upper limb distal to the AVF during second post-operative week due to a complex regional pain syndrome (CRPS). CRPS is characterized by pain that is disproportionate to the invoking injury, autonomic dysfunction, trophic changes and functional impairment of affected limb. Hyperalgesia and allodynia are pain patterns characteristic of CRPS. CRPS has been reported rarely following AVF creation surgery. Prompt diagnosis of CRPS is important to avoid misdiagnosis of vascular disorders and for implementation of right therapeutic strategy.

Glomus Tumor of the Lower Extremity Previously Misdiagnosed as Complex Regional Pain Syndrome in Close Proximity to a Myxofibrosarcoma: A Case Report.

Complex regional pain syndrome (CRPS) is a potentially devastating condition that can result in severe psychological and social morbidity. It is a diagnosis of exclusion, and other pathologic entities must be ruled out first. Glomus tumors are exquisitely painful benign vascular tumors that are most common in the hand and are rarely found in the lower extremity. Here, we present a case of a patient who developed a focus of severe anterior knee pain and tenderness a few months after a car accident that had been misdiagnosed as CRPS for 15 years. She coincidentally developed a sarcoma of her ipsilateral leg distal to this site. Magnetic resonance imaging of the sarcoma included the area of knee pain where, interestingly, it identified a separate small soft-tissue mass. A glomus tumor was diagnosed histologically in a needle biopsy specimen from this mass, which was resected along with the sarcoma. For the first time in 15 years, despite the additional sarcoma surgery, she reported relief of her pain and complete resolution of her "CRPS."

Relative Prevalence and Associated Factors of Complex Regional Pain Syndrome Type I in Patients with Radial Head Fractures Treated with Open Reduction and Internal Fixation: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to examine the incidence and associated factors of complex regional pain syndrome type I (CRPS I) in patients who underwent open reduction and internal fixation (ORIF) for radial head fractures. Methods: The study enrolled 601 radial head fracture patients treated with ORIF, 523 of which completed the 1-year follow-up. The incidence of CRPS I in those patients was assessed using the Budapest criteria. Patients were then divided into 2 groups: patients with CRPS I (n = 28) and patients without CRPS I (n = 495). The patients' demographic and clinical data before the operation were prospectively collected by our team. Independent t-tests and χ 2 tests were used as univariate analyses to compare the demographic and clinical data between the two groups. Meanwhile, multivariate regression analysis was conducted to identify the associated risk factors for CRPS I. Results: The incidence of CRPS I in patients with radial head fractures treated with ORIF was 5.5% during the first year following surgery. Significant differences were observed in age, gender, type of trauma, modified Mason Classification, and depressive personality disorders. The logistic regression analysis revealed that the female gender, modified Mason type III fractures, and depressive patients were significantly more likely to develop CRPS I (p=0.021, 0.023, and 0.025, respectively). Conclusions: The incidence of CRPS I among radial head fracture patients undergoing ORIF was 5.5%. In addition, early detection of CRPS I and providing adequate intervention will likely result in greater benefits for those patients.

Atypical dermatologic manifestations in complex regional pain syndrome: a case report.

BACKGROUND: Complex regional pain syndrome is a chronic pain condition characterized by autonomic dysfunction, changes in sympathetic and vasomotor activity, and sensory and motor changes. Complex regional pain syndrome is a clinical diagnosis and may occur after trauma or surgery. Complex regional pain syndrome-related pain may occur spontaneously and is out of proportion with the inciting event. We report herein the rare case of a man who developed concomitant painful generalized ulcerations after diagnosis of complex regional pain syndrome. CASE PRESENTATION: A 43-year-old Caucasian male with history of four-extremity complex regional pain syndrome type 2 secondary to right rotator cuff surgery performed at an outside hospital presented to a tertiary care center for treatment of generalized ulcerations on all extremities of unknown etiology. Dermatology performed an extensive work-up including laboratory evaluations and biopsies, which were relatively unremarkable. His ulcers were treated with vinegar-based dressings, hydrotherapy, and irrigation and debridements. He was started on methadone (replacing a home fentanyl patch), ketamine infusion, and amitriptyline in addition to his home adjuncts. He obtained good symptom control, improved sleep, and diminished cognitive slowing, compared with his fentanyl patches. CONCLUSION: This case report emphasizes an atypical case of generalized ulceration formation in the setting of complex regional pain syndrome. This case highlights the challenging nature of treating complex regional pain syndrome and using multimodal analgesia to target various nociceptive receptors to successfully reduce symptoms.

Complex Regional Pain Syndrome after Carpal Tunnel Syndrome Surgery: A Systematic Review.

Background: Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment. One of the most devastating complications is complex regional pain syndrome. Objectivities: The aim of this study was to systematically analyze available evidence about complex regional pain syndrome after carpal tunnel syndrome surgery (CTSS), its risks, associated factors, and treatments. Material and Methods: Research conducted from 1962 through December 31, 2018, in the following databases: PubMed, Web of Science, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. The quality assessment of the methodology followed the definitions by the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. The GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) was applied to evaluate the efficacy of the stellate ganglion block, one of the most cited and recurrent treatments. Results: Of the 246 studies retrieved, 44 articles were included. Concerning patients' gender, we identified a ratio of 5 females: 3 males. The mean age for women was 57.79, a standard deviation of 14.96, and for men 60.75, a standard deviation of 9.4. Considering the total of primary publications of CTSS outcomes, the accumulated incidence reached the maximum of 0.15 CRPS after CTSS patients/CTSS patients. The known risk factors for CRPS after CTSS: female gender, from the fifth decade of life, tourniquet time, immobilization and surgery on dominant hand. Conclusion: CRPS affects 2-5% of people undergoing CTSS. Its diagnosis is still a challenge and its risk factors are unclear, although it seems more likely to affect women, in the dominant hand. The most used treatments include physiotherapy and stellate ganglion block. Most patients show improvement of symptoms within one year. Further clinical trials comparing treatment modalities are required.

Outcomes of Carpal Tunnel Release in Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy/Sudeck Disease Patients.

BACKGROUND: The clinical features of classic carpal tunnel syndrome are well known. However, some patients who display atypical symptoms and signs of pain and dysesthesias in the hand, worsening of symptoms at night, and above all, inability to make a full fist, respond equally well to carpal tunnel release. This same clinical picture was shared by some patients labeled as having complex regional pain syndrome. Because of the poor outcome of complex regional pain syndrome patients with current regimens, the authors tested the hypothesis that carpal tunnel release could be effective on them. The purpose of this article is to report the outcome of carpal tunnel release in complex regional pain syndrome patients who presented the above signs and symptoms. METHODS: Fifty-three patients with an average age of 55 years presenting the above cluster of symptoms were operated on. All were unilateral cases, had sustained trauma, and were treated for complex regional pain syndrome before referral for an average of 16 months. All patients underwent carpal tunnel release. RESULTS: At a minimum of 6 months' follow-up, pain dropped 7.5 points on a numerical rating scale of 0 to 10 ( p < 0.001). Disabilities of the Arm, Shoulder and Hand scoring fell from 82 to 17 ( p < 0.001). Six patients had an unsatisfactory result. CONCLUSIONS: Some patients with complex regional pain syndrome may respond successfully to a carpal tunnel release operation. Recognition of this possibility is crucial, as the symptoms and signs might lead the clinician away from the proper diagnosis and treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P's < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P's < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P's < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P's < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

First case report of Pacinian corpuscle hyperplasia following complex regional pain syndrome.

Pacinian disorders are exceedingly rare, and the exact pathogenesis is still unknown. The most common symptoms are pain, sensory changes, and a visible or palpable mass, and diagnosis is usually made by pathological examination after the excision of the painful nodule. In this case report, we present the case of a 49-year-old male with Pacinian corpuscle hyperplasia located on the metacarpophalangeal joint, emerging at the same hand of the patient two years after the treatment due to complex regional pain syndrome (CRPS). To the best of our knowledge, this is the first case report revealing the association of CRPS with hyperplasia of Pacinian corpuscles.

Effect of Perioperative Vitamin C on the Incidence of Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome type 1 (CRPS-I) is a complex complication that occurs after limb extremity surgeries. Controversy exists regarding the effectiveness of vitamin C in reducing that condition. Therefore, we conducted this systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. We searched Medline (via PubMed), Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar for relevant studies comparing perioperative vitamin C versus placebo after distal radius, wrist, foot, and ankle surgeries from infinity to May 2021. Continuous data such as functional outcomes and pain scores were pooled as mean differences, while dichotomous variables such as the incidence of complex regional pain syndrome and complications were pooled as odds ratios, with 95% confidence interval, using R software (meta package, version 4.9-0) for Windows. Eight studies were included. The timeframe for vitamin C administration in each study ranged from 42 to 50 days postinjury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo (odds ratio 0.33, 95% confidence interval [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (odds ratio 1.90, 95% confidence interval [0.99, 3.65]), functional outcomes (mean difference 6.37, 95% confidence interval [-1.40, 14.15]), and pain scores (mean difference -0.14, 95% confidence interval [-1.07, 0.79]). Overall, vitamin C was associated with a decreased rate of CRPS-I than placebo, while no significant difference was found regarding complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g).

Separating Fact From Fiction: A Nationwide Longitudinal Examination of Complex Regional Pain Syndrome Following Treatment of Dupuytren Contracture.

BACKGROUND: One of the most feared complications following treatment of Dupuytren contracture is complex regional pain syndrome (CRPS). This study aims to provide a national perspective on the incidence of CRPS following treatment of Dupuytren contracture and identify patient factors to target for risk reduction. METHODS: Using the Truven MarketScan databases from 2007 to 2016, individuals aged ≥18 years who developed CRPS within 1 year of treatment of Dupuytren contracture were identified using the International Classification of Disease diagnosis code for CRPS. Predictor variables included: age, sex, employment status, region, type of procedure, and concurrent carpal tunnel surgery. Multivariable logistic regression was used to analyze outcomes. RESULTS: In all, 48 327 patients received treatment for Dupuytren contracture, including collagenase injection (13.6%); percutaneous palmar fasciotomy (10.3%); open palmar fasciotomy (3.9%); palmar fasciectomy with 0 (10.8%), 1 (29.2%), or multiple (19.6%) digit releases; or a combination of these procedures (12.8%). One hundred forty-five patients (0.31%) were diagnosed with CRPS at a mean of 3.4 months (standard deviation, 2.3) following treatment. Significant predictors of CRPS included female sex (odds ratio [OR], 2.02; P < .001), Southern region (OR, 1.80; P = .022), long-term disability status (OR, 4.73; P = .035), palmar fasciectomy with release of 1 (OR, 5.91; P = .003) or >1 digit (OR, 13.32; P < .001), or multiple concurrent procedures for Dupuytren contracture (OR, 8.23; P = .001). CONCLUSIONS: Based on national commercial claims data, there is a lower incidence of CRPS following treatment of Dupuytren contracture than previously reported. Risk factors identified should help with preoperative counseling and assist clinicians in targeting risk reduction measures.

The autoimmune aetiology of unexplained chronic pain.

Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as 'chronic primary pains' (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, 'nociplasticic pain' has been developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system. Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pain associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble those of the clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the molecular and cellular details. The central nervous system appears largely unaffected by antibody binding, suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream of peripheral processes. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms.