Defining the link between peripheral neuronal activity and neuropathic pain: observational study protocol to investigate in vivo neurophysiological properties of nociceptors in patients with chronic neuropathic pain
Abstract
Introduction: Neuropathic pain affects up to 10% of the population and remains difficult to diagnose and treat effectively. Peripheral nociceptor hyperexcitability is thought to drive pain in a substantial subset of patients, yet human studies have not fully defined which nociceptor populations are abnormal or how these abnormalities relate to clinical phenotype, sensory profiling, or genetic mechanisms. Microneurography uniquely enables direct in vivo recording from human C-fibres, offering a mechanistic approach to patient stratification. This observational study investigates the relationships between neuropathic pain, nociceptor excitability, somatosensory phenotype, and genetic variation.
Methods and analysis: We will conduct an observational controlled study at the University of Oxford (2022-2029) following STROBE guidelines. Adults with and without neuropathy or neuropathic pain will undergo deep phenotyping, including questionnaires, neurological examination, quantitative sensory testing, nerve conduction studies, microneurography, skin biopsy, and genetic and transcriptomic analyses. Microneurography recordings will quantify C-fibre axonal properties, excitability, spontaneous activity, and responses to electrical, thermal, and mechanical stimulation. Participants will be stratified by neuropathy grade, neuropathic pain status, somatosensory phenotype, and genetic variants. Primary analyses will compare axonal excitability and related microneurography measures…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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