A novel injectable hydrogel that slowly releases dexamethasone and mepivacaine provided sustained pain relief for at least 14 days in rats with nerve injury, while significantly reducing expression of pain-related neuropeptide CGRP.
Pain relief sustained for 14+ daysThe hydrogel significantly reduced both cold and mechanical pain sensitivity in nerve-injured rats from day 7 through at least day 14, while also lowering expression of the pain neuropeptide CGRP.
What the researchers found
The CHA-DEX-MEPI hydrogel demonstrated sustained release of both dexamethasone and mepivacaine for more than 72 hours, compared to rapid clearance with standard solution injections.
In activated macrophages, the hydrogel prolonged reduction of inflammatory cytokine gene expression for three days compared to a simple drug solution.
In rats with chronic constriction nerve injury, the hydrogel significantly reduced both cold and mechanical allodynia (pain from normally non-painful stimuli) beginning seven days post-injury. At 14 days post-injury, the hydrogel produced sustained reductions in key nociceptive markers including TRPV1, TRPA1, and importantly CGRP — a neuropeptide directly involved in pain transmission and neurogenic inflammation.
Why it matters
Chronic neuropathic pain affects millions of people and is notoriously difficult to treat. Current epidural injections provide temporary relief but require frequent repeat procedures and can cause side effects from uncontrolled drug spread. A hydrogel that keeps medications exactly where they're needed and releases them slowly could extend pain relief from hours to weeks, potentially reducing the number of procedures needed and improving quality of life for chronic pain patients.
How the study worked
The hydrogel was synthesized by combining glycolic chitosan and oxidized hyaluronic acid, which self-crosslink to form an injectable gel. Dexamethasone and mepivacaine were embedded within the gel matrix. In vitro testing used bone marrow-derived macrophages activated with LPS to assess anti-inflammatory duration. In vivo testing used the chronic constriction injury (CCI) model in Sprague-Dawley rats, with pain responses measured over 14 days using cold and mechanical allodynia tests. Nociceptive marker expression (TRPV1, TRPA1, CGRP) was assessed at 14 days post-injury.
What this study cannot tell us
This is an animal study using a surgically induced nerve injury model, which may not fully represent the diverse causes of neuropathic pain in humans. The 14-day follow-up is relatively short for a chronic pain condition. Specific drug concentrations in the hydrogel and exact release kinetics are not fully detailed in the abstract. The sample size per group is not specified. Safety and biocompatibility data beyond the 14-day period are not reported. Translation to human epidural use would require extensive safety testing.
How to read the evidence
This is a preclinical animal study demonstrating proof of concept for a novel drug delivery system. The combination of in vitro and in vivo data with multiple endpoints (pain behavior, inflammatory markers, nociceptive markers) strengthens the evidence, but translation to human clinical use remains distant.
When this study was published
Published in 2025, this is a very recent study representing current advances in biomaterial-based pain management. The technology would need years of further development and clinical testing before potential human application.
The bigger picture
The intersection of biomaterials and pain management is a growing field. CGRP has become a major target in pain medicine — anti-CGRP antibodies are already approved for migraine prevention. This hydrogel takes a different approach by using sustained-release anti-inflammatory drugs to reduce CGRP expression at the source of nerve injury, rather than blocking CGRP systemically. The concept of locally controlled, sustained neuropeptide modulation could complement existing systemic anti-CGRP therapies.
Questions still open
- Could this hydrogel be combined with specific anti-CGRP agents instead of traditional steroids for even more targeted neuropeptide-based pain relief?
- How long does the pain relief actually last beyond the 14-day observation period?
- Would this sustained-release approach work for other types of chronic pain beyond nerve injury, such as postsurgical or inflammatory pain?
Common questions
What is CGRP's role in pain and why does reducing it matter?
How is this different from a regular epidural steroid injection?
Read the original research
Injectable glycol chitosan hydrogel system for sustained drug delivery to treat neuropathic pain.
International journal of biological macromolecules, 333(Pt 1), 148757
Citation
Lee, Daye; Han, Gong Ho; Kim, Seong Jun; Ko, Wan-Kyu; Kim, Min Je; Ju, Gi-Beom; Sheen, Seung Hun; Hong, Je Beom; Cho, Min Jai; Sohn, Seil. (2025). Injectable glycol chitosan hydrogel system for sustained drug delivery to treat neuropathic pain.. International journal of biological macromolecules, 333(Pt 1), 148757. https://doi.org/10.1016/j.ijbiomac.2025.148757