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

IF 3.5 2区 医学 Q1 ANESTHESIOLOGY
Jorge Luiz Dallazen, Larissa Gonzaga Santos, Simone Aparecida Teixeira, Gilberto De Nucci, Marcelo Nicolás Muscará, Soraia Katia Pereira Costa
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Abstract

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.

阐明内源性硫化氢作为小鼠术后疼痛恢复新候选物的意义
硫化氢(H2S)被认为是炎症性疾病的关键调节因子;然而,它在术后疼痛的复杂病理生理学中的作用经常被错误地处理。本研究旨在通过小鼠术后疼痛模型阐明内源性H2S在伤害性阈值恢复中的作用。方法雄性BALB/c小鼠(6 ~ 7周龄)采用假或足底切开手术(PIS)。术前和pis后1-7天评估热阈值和力学阈值。在pis后1、4和7 d,测定内源性H2S的产量及其合成酶——胱硫氨酸β合酶(CBS)、胱硫氨酸γ裂解酶(CSE)和3-巯基丙酮酸硫转移酶(3-MPST)的表达。结果pis后1天,术后后爪H2S生成减少,机械痛敏和热痛敏分别持续5天和6天。术后后爪CSE表达减少,而CBS在第1天在坐骨神经和第4天在L4-L5脊髓节段表达增加。3-MPST的表达保持不变。足底注射氨基乙酸(AOAA)或dl-丙基甘氨酸(PGly), CSE/CBS活性抑制剂,显著延迟伤害阈值恢复。我们的研究结果表明,虽然通过CSE的H2S信号在术后疼痛恢复中发挥的作用有限,但针对CBS活动来保持内源性H2S水平可能是增强疼痛和加速恢复的有希望的替代方法。针对CBS维持H2S信号提供了一种新的策略来增强术后疼痛恢复。
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来源期刊
European Journal of Pain
European Journal of Pain 医学-临床神经学
CiteScore
7.50
自引率
5.60%
发文量
163
审稿时长
4-8 weeks
期刊介绍: European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.
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