Elucidating the Significance of Endogenous Hydrogen Sulfide as a Novel Candidate for Postoperative Pain Recovery in a Murine Model.

BACKGROUND

Hydrogen sulfide (H2S) is proposed to be a key regulator of inflammatory diseases; however, its role in the complex and often inadequately managed pathophysiology of postoperative pain is frequently mishandled. This study was undertaken to elucidate the role of endogenous H2S in the recovery of nociceptive thresholds using a mouse model of postoperative pain.

METHODS

Male BALB/c mice (6-7 weeks) underwent sham or plantar incision surgery (PIS). Thermal and mechanical thresholds were assessed before surgery and 1-7 days post-PIS. At 1, 4 and 7 days post-PIS, the endogenous production of H2S and the expression of its synthesising enzymes-cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MPST)-were evaluated.

RESULTS

One day post-PIS, a reduction in H2S production was observed in the operated hindpaw, with mechanical and thermal hyperalgesia lasting 5 and 6 days, respectively. CSE expression decreased in the operated hindpaw, while that of CBS increased on day 1 in the sciatic nerve and on day 4 in the L4-L5 spinal cord segments. The expression of 3-MPST remained unchanged. Intraplantar injection of aminooxyacetic acid (AOAA) or dl-propargylglycine (PGly), inhibitors of CSE/CBS activity, significantly delayed nociceptive threshold recovery.

CONCLUSION

Our findings suggest that while H2S signalling via CSE appears to play a limited role in postoperative pain recovery, targeting CBS activity to preserve endogenous H2S levels may offer a promising alternative for enhancing pain and accelerating recovery.

SIGNIFICANCE STATEMENT: Targeting CBS to sustain H2S signalling offers a new strategy to enhance postoperative pain recovery.