Biochemical markers in chronic pain and peripheral nerve entrapment: potential mechanistic links to ultrasound-guided nerve hydrodissection: a structured narrative review

Objective To review the biochemical and inflammatory markers implicated in chronic pain and peripheral nerve entrapment, and to evaluate the biochemical rationale, proposed injectate mechanisms, and current clinical applications of ultrasound-guided nerve hydrodissection (US-HD) as they relate to these markers. Methods This structured narrative review was conducted using a literature search strategy across PubMed/MEDLINE-indexed and major publisher-hosted literature. Structured searches using eleven pre-specified query strings were run against PubMed/MEDLINE-indexed and major publisher-hosted literature (Frontiers, MDPI, Nature Portfolio, Wolters Kluwer, Springer Nature, Cureus), combining “hydrodissection”, “perineural injection” and “nerve entrapment” with “biochemical marker”, “biomarker”, “inflammatory cytokine” and named mediators (IL-6, TNF-α, VEGF, substance P, CGRP, NGF, kynurenine, TRPV1). Of 81 records identified, 64 remained after de-duplication; following title/abstract screening and full-text assessment against pre-defined eligibility criteria, 13 studies were included in the qualitative synthesis. Results Elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), angiogenic mediators (VEGF) and fibrotic markers (TGF- β 1, BMP-7) are associated with nerve entrapment syndromes such as carpal tunnel syndrome (CTS). Neuropeptide and neurotrophic markers, including substance P, CGRP and nerve growth factor (NGF), alongside kynurenine pathway metabolites, are implicated in the maintenance of chronic and neuropathic pain. Mechanistically, dextrose-based hydrodissection injectate is proposed to downregulate TRPV1 receptor activity, while platelet lysate/platelet-rich plasma (PRP) injectate delivers growth factors and may modulate local cytokine profiles. Clinical studies report improvements with US-HD across CTS, myofascial pain syndrome, ulnar neuropathy and knee osteoarthritis, however, the evidence base is small and heterogeneous; no included study measured biochemical markers before and after hydrodissection. Conclusion Biochemical markers provide a plausible mechanistic framework for US-HD, but direct evidence linking biomarker change to hydrodissection or clinical improvement is absent. Proposed injectate mechanisms therefore remain theoretical. Prospective studies incorporating pre- and post-procedural biomarker sampling are needed to bridge this gap.