脊髓白细胞介素-10/β-内啡肽通路抑制幼年大鼠神经病理性疼痛

Spinal Interleukin-10/β-Endorphin Pathway Suppresses Neuropathic Pain in Infant Rats

【目的】探究幼年大鼠经历外周神经损伤后不发生神经病理性疼痛反应的生理机制。【方法】为出生10 d或33 d大鼠构建坐骨神经分支选择性损伤(SNI)诱导的神经病理性疼痛模型,术后7 d检测后肢机械痛阈值并用实时荧光定量PCR检测脊髓白细胞介素-10(IL-10)和β-内啡肽前体阿黑皮素原(POMC)基因表达水平。出生10 d幼年大鼠构建SNI模型后7 d,连续3 d鞘内注射生理盐水或IL-10抗体或β-内啡肽抗体,每次注射后1 h检测后肢机械痛阈值。实时荧光定量PCR检测脊髓IL-10和POMC基因表达水平。【结果】与成年大鼠神经损伤后的表现相反,幼年大鼠SNI术后7 d不表现疼痛超敏,脊髓IL-10和POMC基因表达升高。鞘内注射IL-10抗体和β-内啡肽抗体能够引发幼年大鼠机械痛超敏;鞘内注射IL-10抗体能拮抗SNI引起的幼年大鼠脊髓POMC基因表达升高,而相反注射β-内啡肽抗体则不影响IL-10基因的表达。【结论】幼年大鼠神经病理性疼痛反应缺失与其脊髓IL-10/β-内啡肽通路激活有关。

【Objective】To unmask the mechanisms underlying the suppression of infant neuropathic pain after peripheral nerve injury.[ Methods] Rats were subjected to spared nerve injury( SNI) at postnatal 10 d or 33 d. Mechanical paw withdrawal thresholds as well as spinal interleukin-10( IL-10) and the β-endorphin precursor gene proopiomelano cortin(POMC) mRNA expression were detected 7 d after surgery. The IL-10 or β-endorphin neutralizing antibody was intrathecally injected for 3 d(the 7th-9th day after surgery) and mechanical paw withdrawal thresholds were tested 1 h after each injection. Spinal IL-10 mRNA and POMC mRNA were detected by RT-qPCR.[R esults] In contrast to adult rats,infant rats subjected to SNI displayed no mechanical allodynia but an increase in spinal cord IL- 10 and POMC mRNA expression. Intrathecal administration of the IL-10 antibody and β-endorphin antibody evoked neuropathic pain- like behaviors in infant rats. SNI-induced POMC mRNA increase was blocked by the pretreatment with intrathecal the IL- 10 antibody,while the increased IL-10 mRNA expression was not affected by the β-endorphin antibody pretreatment.[Conclusions] The suppression of neuropathic pain in infant rats may be mediated by activation of spinal IL-10/β-endor phin pathway.