Nerve pathology and neuropathic pain after whiplash injury: a systematic review and meta-analysis

There is no clear understanding of the mechanisms causing persistent pain in patients with whiplash associated disorder (WAD). The aim of this systematic review was to assess the evidence for nerve pathology and neuropathic pain in patients with WAD. EMBASE, PubMed, CINAHL (EBSCO), and MEDLINE were searched from inception to 1st September 2020. Study quality and risk of bias were assessed using the Newcastle-Ottawa Quality Assessment Scales. Fifty-four studies reporting on 390,644 patients and 918 controls were included. Clinical questionnaires suggested symptoms of predominant neuropathic characteristic in 34% of patients (range 25-75%). Mean prevalence of nerve pathology detected with neurological examination was 13% (0-100%) and 32% (10-100%) with electrodiagnostic testing. Patients independent of WAD severity (Quebec Task Force grades I-IV) demonstrated significantly impaired sensory detection thresholds of the index finger compared to controls, including mechanical (SMD 0.65 [0.30;1.00] p< 0.005), current (SMD 0.82 [0.25;1.39] p=0.0165), cold (SMD -0.43 [-0.73;-0.13] p=0.0204) and warm detection (SMD 0.84 [0.25;1.42] p=0.0200). Patients with WAD had significantly heightened nerve mechanosensitivity compared to controls upon median nerve pressure pain thresholds (SMD -1.10 [-1.50;-0.70], p<0.0001) and neurodynamic tests (SMD 1.68 [0.92;2.44], p=0.0004). Similar sensory dysfunction and nerve mechanosensitivity was seen in WAD grade II, which contradicts its traditional definition of absent nerve involvement. Our findings strongly suggest a subset of patients with WAD demonstrate signs of peripheral nerve pathology and neuropathic pain. Although there was heterogeneity among some studies, typical WAD classifications may need to be reconsidered and include detailed clinical assessments for nerve integrity.