Biochemical Markers May Explain How Nerve Hydrodissection Eases Chronic Pain

The review was conducted to examine 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 as they relate to these markers. A structured narrative review now maps the biochemical terrain underlying both problems and asks whether ultrasound-guided nerve hydrodissection, a technique that injects fluid around trapped nerves, can be explained by what is known about inflammatory and neurotrophic markers. The review, published in Frontiers in Pain Research, screened 81 records and included 13 studies in its qualitative synthesis, yet its most striking conclusion is a negative one: not a single included study measured biochemical markers before and after hydrodissection.

The search strategy combined terms such as hydrodissection, perineural injection and nerve entrapment with biochemical marker, biomarker, inflammatory cytokine and named mediators including IL-6, TNF-α, VEGF, substance P, CGRP, NGF, kynurenine and TRPV1. The queries ran against PubMed/MEDLINE-indexed and major publisher-hosted literature, including Frontiers, MDPI, Nature Portfolio, Wolters Kluwer, Springer Nature and Cureus. After de-duplication left 64 records, title and abstract screening and full-text assessment against pre-defined eligibility criteria narrowed the field to the 13 studies that formed the evidence base.

The included studies reported associations between biochemical markers and nerve entrapment syndromes such as carpal tunnel syndrome. Elevated pro-inflammatory cytokines, specifically IL-1β, IL-6 and TNF-α, are associated with nerve entrapment syndromes such as carpal tunnel syndrome. Angiogenic mediators, notably vascular endothelial growth factor, and fibrotic markers including TGF-β1 and BMP-7, also appear in this context. Elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), angiogenic mediators (VEGF) and fibrotic markers (TGF-β1, BMP-7) are associated with nerve entrapment syndromes such as carpal tunnel syndrome.

Neuropeptide and neurotrophic markers, including substance P, CGRP and nerve growth factor, alongside kynurenine pathway metabolites, are implicated in the maintenance of chronic and neuropathic pain. Neuropeptides such as substance P and CGRP, the neuropeptide associated with migraine and neurogenic inflammation, are implicated in the maintenance of chronic and neuropathic pain, alongside nerve growth factor and metabolites of the kynurenine pathway.

The review evaluated ultrasound-guided nerve hydrodissection, a technique in which fluid is injected around a nerve, as it relates to these markers. The technique has been applied to carpal tunnel syndrome, ulnar neuropathy, myofascial pain syndrome and knee osteoarthritis, and clinical studies report improvements across these conditions. The review notes that 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.

The biochemical explanations for why the injectate itself might matter are more speculative. Dextrose-based hydrodissection injectate is proposed to downregulate TRPV1 receptor activity. Dextrose-based hydrodissection injectate is proposed to downregulate TRPV1 receptor activity. Platelet lysate/platelet-rich plasma (PRP) injectate delivers growth factors and may modulate local cytokine profiles. The review is explicit that these mechanisms remain theoretical: because no included study measured biomarkers before and after the procedure, there is no direct evidence linking any biochemical change to hydrodissection or to clinical improvement.

The review concludes that biochemical markers provide a plausible mechanistic framework for US-HD, but direct evidence linking biomarker change to hydrodissection or clinical improvement is absent. The clinical improvements reported across carpal tunnel syndrome, myofascial pain syndrome, ulnar neuropathy and knee osteoarthritis come from a small and heterogeneous evidence base, and the review does not claim that hydrodissection works through any specific molecular pathway. What the biochemical literature provides is a plausible framework: if entrapment syndromes are characterized by elevated cytokines, angiogenic activity and fibrosis, and if chronic pain is maintained by neuropeptides and neurotrophic factors, then a procedure that alters the perineural environment could plausibly interact with those systems. The review concludes that proposed injectate mechanisms therefore remain theoretical.

The review’s authors argue that prospective studies incorporating pre- and post-procedural biomarker sampling are needed to bridge the gap between mechanism and outcome. The review states that prospective studies incorporating pre- and post-procedural biomarker sampling are needed to bridge this gap. The authors also note that the evidence base is small and heterogeneous, which limits the strength of any conclusion about clinical efficacy.

Subject of Research: Biochemical markers implicated in chronic pain and peripheral nerve entrapment and their potential mechanistic links to ultrasound-guided nerve hydrodissection

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

Article References: McGrath, H., King, S., Quinton, M., Mullins, C. F., & Harmon, D. (2026). Biochemical markers in chronic pain and peripheral nerve entrapment: potential mechanistic links to ultrasound-guided nerve hydrodissection: a structured narrative review. Frontiers in Pain Research, 7, Article 1964102. https://doi.org/10.3389/fpain.2026.1964102

Image Credits: AI Generated

DOI: 10.3389/fpain.2026.1964102

Keywords: chronic pain, nerve entrapment, carpal tunnel syndrome, hydrodissection, inflammatory cytokines, biomarkers, neuropathic pain, ultrasound-guided injection, substance P, CGRP, nerve growth factor, TRPV1