Continence (Dec 2023)
MTHFR mutation
Abstract
Introduction and Objective:: Chronic pelvic pain (CPP) is a heterogeneous condition with multiple etiologies. Better characterization and understanding of CPP will lead to new therapeutic options and individualization of care, especially in patients with chronic overlapping pain syndromes (COPCs), which increase complexity of diagnosis. In this study, we present 6 patients with COPC and complex CPP, non-focal exam, who tested negative for small fiber neuropathy but who reported a history of methylenetetrahydrofolate reductase (MTHFR) mutations, and retrospective review of 76 patients with MTHFR mutation. This study explores through literature review whether MTHFR mutations play a role in the pathogenesis of chronic pelvic pain and overlapping pain conditions in a subset of patients with COPCs. Methods:: Study design included an observational study of 6 patients, a retrospective cross-sectional study of 76 patients, and a literature review. Patients at our institution who tested positive for MTHFR mutations were included in the study; most had been seen in the cardiology/hematology clinics due to the association of MTHFR with clotting disorders. Chart review was performed to identify the presence of pain syndromes and specifically CPP. A review of the literature was undertaken to form a hypothesis for mechanisms that could explain the association between MTHFR mutations and chronic overlapping pain syndromes. Results:: Of 76 patients with MTHFR mutations seen primarily in non-pain focused cardiology visits, 30 (39%) had some form of pain syndrome documented, 11 of whom (14%) specifically had CPP. The review below suggests that MTHFR plays a role in the maintenance of nerve tissue and conductance, neural tube defects, and paresthesia. Literature review revealed that MTHFR mutations have been linked with chronic pain and pathological processes such as chronic migraine, interstitial cystitis/bladder pain syndrome, sequelae of chronic Lyme disease, and fibromyalgia. Conclusions:: The etiology of chronic pelvic pain is complex. Multisystem pain extending beyond the pelvis complicates the differential diagnosis but suggests a systemic cause. MTHFR mutations may play a unifying role in a subset of chronic pelvic pain patients with concomitant chronic overlapping pain syndromes. The mutations may affect folate metabolism pathways in these patients and hinder the ability to maintain nerve fibers over time, leading to dereliction of pain signal conduction. Disturbance of these pathways may have a role in chronic overlapping pain syndromes and complex pelvic pain.
