Causalgia: A Review of Nerve Resection, Amputation, Immunotherapy, and Amputated Limb CRPS II Pathology.

BACKGROUND: Causalgia and complex regional pain syndrome (CRPS) type II with nerve injury can be difficult to treat. Surgical peripheral nerve denervation for causalgia has been largely abandoned by pain clinicians because of a perception that this may aggravate a central component (anesthesia dolorosa). METHODS: We selectively searched Pubmed, Cochrane, MEDLINE, EMBASE, CINAHL Plus, and Scopus from 1947 for articles, books, and book chapters for evidence of surgical treatments (nerve resection and amputation) and treatment related to autoimmunity and immune deficiency with CRPS. RESULTS: Reviews were found for the treatment of causalgia or CRPS type II (n = 6), causalgia relieved by nerve resection (n = 6), and causalgia and CRPS II treated by amputation (n = 8). Twelve reports were found of autoimmunity with CRPS, one paper of these on associated immune deficiency and autoimmunity, and two were chosen for discussion regarding treatment with immunoglobulin and one by plasma exchange. We document a report of a detailed and unique pathological examination of a CRPS type II affected amputated limb and related successful treatment with immunoglobulin. CONCLUSIONS: Nerve resection, with grafting, and relocation may relieve uncomplicated causalgia and CRPS type II in some patients in the long term. However, an unrecognized and treatable immunological condition may underly some CRPS II cases and can lead to the ultimate failure of surgical treatments.

Corrigendum: A role for pathogenic autoantibodies in small fiber neuropathy?

[This corrects the article DOI: 10.3389/fnmol.2023.1254854.].

A role for pathogenic autoantibodies in small fiber neuropathy?

The immune system has a role in neuropathic pain which includes autoimmune mechanisms (e.g., autoantibodies). Clinical studies have identified a number of conditions where neuropathic pain is common and that are associated with autoantibodies targeting antigens within the nervous system. Interestingly sensory symptoms can be relieved with immunotherapies or plasma exchange, suggesting that pain in these patients is antibody-mediated. Recent preclinical studies have directly addressed this. For example, passive transfer of CASPR2 autoantibodies from patients cause increased pain sensitivity and enhanced sensory neuron excitability in mice confirming pathogenicity and demonstrating that patient autoantibodies are a mechanism to cause neuropathic pain. Small fiber neuropathy (SFN) exclusively affects small sensory fibers (typically nociceptors) and is characterized by severe neuropathic pain. Known causes include diabetes, B12 deficiency and rare variants in sodium channel genes, although around 50% of cases are idiopathic. SFN is associated with autoimmune conditions such as Sjorgen's syndrome, Sarcoidosis and Celiac disease and immunotherapy in the form of Intravenous immunoglobulin (IVIG) has proved an effective treatment. Autoantibodies have been identified and, in some cases, passive transfer of SFN patient IgG in mice can recapitulate neuropathic pain-like behavior. Here we will discuss clinical and preclinical data relating to the idea that pathogenic autoantibodies contribute to SNF. We discuss putative pathogenic antibodies, cellular targets and the molecular mechanisms by which they cause sensory neuron damage and the development of neuropathic pain. Finally, we will comment on future directions which may provide further insights into the mechanisms underlying SFN in patients.

Cross-sectional study of patient satisfaction with oral analgesics in patients with chronic pain in Japan.

BACKGROUND: Chronic pain is often difficult to treat, and many patients are not satisfied with analgesic treatment. The authors assessed patient satisfaction with oral analgesics in patients with chronic pain in Japan. RESEARCH DESIGN AND METHODS: This was an observational cross-sectional study conducted in dispensing pharmacies. A patient satisfaction questionnaire survey was conducted in 781 patients prescribed one nonsteroidal anti-inflammatory drug (NSAID) or neuropathic pain (NeP) drug for at least 90 consecutive days. The primary endpoint was patient satisfaction with analgesics. The secondary endpoints were pain relief, activity of daily living (ADL) improvement and doctor-patient communication. RESULTS: The proportions of patients who answered 'satisfied if anything' or better for patient satisfaction in the NSAID and NeP drug groups were 70.0% and 65.2%, respectively, whereas those of patients who answered 'satisfied' were 43.3% and 29.4%, respectively. The proportions of patients with improved pain relief, ADL improvement, and good doctor-patient communication were numerically higher than those of patients who answered 'satisfied if anything' or better. CONCLUSIONS: Approximately two-thirds of the patients were satisfied with current analgesics. Patient satisfaction with oral analgesics could be influenced by multiple factors. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000036456.