Assessment of diagnostic criteria for centralized pain in amputees undergoing secondary targeted muscle reinnervation

INTRODUCTION: Pain following peripheral nerve injury (PNI) may include a centralized component that may not respond well to peripheral nerve surgery. Evidence-based diagnostic criteria for centralized pain following PNI have been proposed but remain unvalidated. We evaluated whether the presence of centralized pain predicts poorer outcomes following surgery for neuropathic pain.

METHODS: Centralized pain criteria were assessed in prospectively enrolled amputees who underwent secondary targeted muscle reinnervation for pain between 2018-2025, with a minimum of 6-month follow-up. Pain trajectories were analyzed using multilevel mixed-effects models of numeric rating scale scores (0-10). Sustained pain mitigation was defined as a ≥3-point reduction or final pain score ≤3/10 lasting ≥3 months. Five preoperative centralized pain criteria were evaluated: (1) documented PNI, (2) pain >3 months, (3) hypersensitivity beyond the injury zone, (4) mood/cognitive symptoms, and (5) limited response to peripheral nerve block, if performed.

RESULTS: Among 101 patients (median follow-up: 2.5 years (IQR: 1.7-4.1 years)), 70 (69%) achieved sustained pain mitigation. Thirty patients (30%) met all centralized pain criteria. Meeting all the criteria was associated with treatment failure (45% vs. 23%, p=0.043; OR:2.8, 95%CI:1.1-6.9, p=0.026). Test performance showed 45% sensitivity, 77% specificity, 47% positive predictive value, and 76% negative predictive value. Hypersensitivity beyond the injury zone (criterion 3) was independently associated with failure to achieve sustained pain mitigation (42% vs. 21%, p=0.031).

CONCLUSION: Centralized pain predicted worse outcomes following peripheral nerve surgery. The high negative predictive value suggests utility in preoperative risk stratification and patient counseling and supports further clinical validation.

LEVEL OF EVIDENCE: IV - Therapeutic.