Erdosteine Provides Effective Analgesia in Inflammatory Pain Without Impairing Pain Resolution: A Preclinical Comparison With Non-Steroidal Anti-Inflammatory Drugs.

backgroundNonsteroidal anti-inflammatory drugs (NSAIDs) provide effective analgesia but may paradoxically delay tissue recovery, pain resolution and contribute to chronic pain. Erdosteine, a thiol-based prodrug with antioxidant and anti-inflammatory properties, is a mucolytic used for treatment of respiratory diseases but has recently been suggested to possess analgesic potential.

methodsWe examined the analgesic efficacy of erdosteine and its metabolite, Met-1, in experimental models of inflammatory and neuropathic pain and compared its effects with diclofenac and gabapentin. Male mice received complete Freund's adjuvant (CFA) or chronic constriction injury (CCI) to induce inflammatory or neuropathic pain, respectively. Erdosteine (100 or 300 mg/kg, per os), its metabolite MET-1 (intravenous), diclofenac (per os), gabapentin (per os), or vehicle (per os or intravenous as appropriate) were administered for 7 days following CFA or CCI. In separate experiments, treatments were initiated prior to CFA. Mechanical allodynia was quantified by von Frey testing. Plasma levels of CXCL1, S100A8/S100A9, IL-1Ra, and 8-isoprostane were measured by ELISA.

resultsErdosteine significantly reduced CFA-induced allodynia, with efficacy comparable to diclofenac and gabapentin. Unlike diclofenac, erdosteine did not delay pain recovery in post-CFA or pre-CFA experimental settings and did not elevate plasma CXCL1 or 8-isoprostane levels.

conclusionsErdosteine provides robust analgesia in an experimental model of inflammatory pain without disrupting inflammation-resolution pathways or increasing oxidative stress, supporting its potential as a safe, non-opioid analgesic. These findings support further investigation of erdosteine as a potential, non-opioid analgesic drug that does not produce the adverse events associated with NSAIDs. PERSPECTIVE: Erdosteine produced NSAID-comparable analgesia in inflammatory pain without delaying recovery or increasing oxidative and inflammatory markers. Given concerns that NSAIDs may prolong pain resolution, these findings identify erdosteine as a potential non-opioid alternative that relieves inflammatory pain while preserving physiological healing processes. SIGNIFICANCE STATEMENT: Effective and well-tolerated treatments for chronic pain remain limited. Erdosteine is a clinically approved mucolytic with antioxidant and anti-inflammatory properties whose analgesic potential is largely unexplored. We show that oral erdosteine reduces inflammatory pain and allodynia without delaying recovery, unlike the NSAID diclofenac, which increased systemic markers of inflammation and prolonged pain duration. These findings identify erdosteine as a promising candidate for drug repurposing and support further investigation of its potential utility in pain management.