The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p < 0.001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS.

Complex regional pain syndrome (CRPS) is a clinical disorder that is characterized by severe, continuous pain in the affected extremity, which is accompanied by sensory, vasomotor, sudomotor/oedema, and motor/trophic changes. 1. The pain is regionally restricted (i.e. cannot be related to a specific dermatome) and disproportionate to the inciting event. 1,2 CRPS is usually precipitated by trauma (mostly fractures) or surgery. 2,3 The upper extremity is affected more often than the lower extremity. 2-4 CRPS is usually limited to one extremity, though cases of CRPS in multiple extremities have been described. 2 The incidence of CRPS has been reported to range from 5.5 to 26.2 per 100 000 person-years. 3,5 Women are more frequently affected than men, with studies reporting a three-to four-fold higher incidence in women. 3,5 The highest incidence was found in women aged 61-70 yr. 3 Two distinctive forms of CRPS are currently described in the literature: CRPS type I where there is no demonstrable nerve lesion and CRPS type II where there is demonstrable nerve lesion. 1,4,6 CRPS types I and II do not differ in clinical presentation and the choice of treatment. 7 Consequently, CRPS will be used as a general term in this article referring to both CRPS type I and CRPS type II. CRPS can have a severe impact on the quality of life of patients and can lead to substantial physical and social disability. 8,9 It is therefore important for clinicians to recognize and diagnose this disorder in order to provide appropriate care and guidance to patients suffering from this debilitating disease. Key points • Complex regional pain syndrome (CRPS) is a post-traumatic disorder characterized by a nondermatomal distributed, severe, continuous pain in the affected limb and is associated with sensory, motor, vasomotor, sudomotor, and trophic disturbances.

Complex regional pain syndrome (CRPS) is characterized by continuous pain that is often accompanied by sensory, motor, vasomotor, sudomotor, and trophic disturbances. If left untreated, it can have a significant impact on the quality of life of patients. The diagnosis of CRPS is currently based on a set of relatively subjective clinical criteria: the New International Association for the Study of Pain clinical diagnostic criteria for CRPS. There are still no objective laboratory tests to diagnose CRPS and there is a great need for simple, objective, and easily measurable biomarkers in the diagnosis and management of this disease. In this review, we discuss the role of inflammation in the multi-mechanism pathophysiology of CRPS and highlight the application of potential biomarkers of inflammation in the diagnosis and management of this disease.

Complex regional pain syndrome (CRPS) is a debilitating painful condition of a distal extremity that can develop after tissue damage. CRPS is thought to be a multimechanism syndrome and ideally the most prominent mechanism(s) should be targeted by drugs in an individually tailored manner. This review gives an overview of the action and evidence of current and future pharmacotherapeutic options for CRPS. The available options are grouped in four categories by their therapeutic actions on the CRPS mechanisms, i.e. inflammation, central sensitisation, vasomotor disturbances and motor disturbances. More knowledge about the underlying mechanisms of CRPS helps to specifically target important CRPS mechanisms. In the future, objective biomarkers could potentially aid in selecting appropriate mechanism-based drugs in order to increase the effectiveness of CRPS treatment. Using this approach, current and future pharmacotherapeutic options for CRPS should be studied in multicentre trials to prove their efficacy. The ultimate goal is to shift the symptom-based selection of therapy into a mechanism-based selection of therapy in CRPS.

Objectives Ketamine is used to treat chronic refractory pain. However, there are no scientific guidelines for ketamine use in the Netherlands. The aim of this survey was to provide an overview of the use of ketamine for chronic pain in the Netherlands. Methods All pain clinics in the Netherlands were contacted. A digital survey, available from June 2019 to January 2020, was sent to 68 pain clinics. The survey was completed by one pain physician as a representative of the entire pain department. The survey included questions about ketamine treatment indications, administration, dose, duration, treatment repetition and the inpatient or outpatient setting. Results The survey was completed by 51 pain clinics (75.0%). Thirty-one clinics used ketamine for chronic pain treatment. The most common indication was Complex Regional Pain Syndrome (83.9%). Pain clinics administered ketamine via intravenous infusions (96.8%), iontophoresis (61.3%), subcutaneous (3.2%) or oral administration (3.2%). Intravenous ketamine treatment was offered in an inpatient setting in 14 pain clinics, in both an inpatient and outpatient setting in 11 pain clinics and in six pain clinics in an outpatient setting. In the outpatient setting, the median starting dose was 5 mg/h (IQR=17.5–5). The median maximum dose was 27.5 mg/h (IQR=100–11.9). The median infusion duration was 6 h (IQR=8–4). In the inpatient setting, the median starting dose was 5 mg/h (IQR=5–1.5) and the median maximum dose was 25 mg/h (IQR=25–14). Patients were admitted to hospital for a median of 4 days (IQR=5–1). Conclusions The results of this Dutch nationwide survey study show that there are heterogeneous treatment protocols with different indications, treatment setting and dosing regimen for the treatment of chronic pain with ketamine. This study encourages the formulation of a broader consensus and the development of evidence based guidelines for ketamine treatment.