CAJ | 학술논문

目的探讨曲马多对神经病理性痛大鼠中脑远位触液神经元5-HT1A受体表达的影响.方法 SPF级雄性SD大鼠40只,体重220～280 g,采用坐骨神经慢性压迫法制备大鼠神经病理性痛模型,随机分为5组(n=8):正常对照组(C组)、生理盐水组(NS组)、曲马多组(T组)、神经病理性痛+生理盐水组(NP+NS组)和神经病理性痛+曲马多组(NP+T组).C组不行任何处理;NS组和T组仅暴露坐骨神经,分别腹腔注射生理盐水2 ml/kg或曲马多10 mg/kg;NP+NS组和NP+T组制备神经病理性痛模型,模型制备后第7天分别腹腔注射生理盐水2 ml/kg或曲马多10 mg/kg.除C组外,其余4组于腹腔注射曲马多或生理盐水前(T1)和注射后1 h(T2)时测定热痛阈和机械痛阈.于模型制备后第5天,左侧侧脑室注射30%霍乱毒素亚单位B与辣根过氧化物酶复合物(CB-HRP)3μl以标记远位触液神经元,并测定远位触液神经元5-HT1A表达水平.结果与C组比较,NP+NS组中脑远位触液神经元5-HT1A受体表达下调(P＜0.05),其余组差异无统计学意义(P＞0.05);与NS组和T组比较,NP+NS组中脑远位触液神经元5-HT1A受体表达下调,热痛阈和机械痛阈降低,NP+T组热痛阈和机械痛阈降低(P＜0.05),中脑远位触液神经元5-HT1A受体表达差异无统计学意义(P＞0.05);与NP+NS组比较,NP+T组中脑远位触液神经元5-HT1A受体表达上调,热痛阈和机械痛阈升高(P＜0.05).结论曲马多可下调中脑远位触液神经元5-HT1A受体的表达,该作用可能是其减轻大鼠神经病理性痛的机制之一.
목적 탐토곡마다대신경병이성통대서중뇌원위촉액신경원5-HT1A수체표체적영향.방법 SPF급웅성SD대서40지,체중220～280 g,채용좌골신경만성압박법제비대서신경병이성통모형,수궤분위5조(n=8):정상대조조(C조)、생리염수조(NS조)、곡마다조(T조)、신경병이성통+생리염수조(NP+NS조)화신경병이성통+곡마다조(NP+T조).C조불행임하처리;NS조화T조부폭로좌골신경,분별복강주사생리염수2 ml/kg혹곡마다10 mg/kg;NP+NS조화NP+T조제비신경병이성통모형,모형제비후제7천분별복강주사생리염수2 ml/kg혹곡마다10 mg/kg.제C조외,기여4조우복강주사곡마다혹생리염수전(T1)화주사후1 h(T2)시측정열통역화궤계통역.우모형제비후제5천,좌측측뇌실주사30%곽란독소아단위B여랄근과양화물매복합물(CB-HRP)3μl이표기원위촉액신경원,병측정원위촉액신경원5-HT1A표체수평.결과 여C조비교,NP+NS조중뇌원위촉액신경원5-HT1A수체표체하조(P＜0.05),기여조차이무통계학의의(P＞0.05);여NS조화T조비교,NP+NS조중뇌원위촉액신경원5-HT1A수체표체하조,열통역화궤계통역강저,NP+T조열통역화궤계통역강저(P＜0.05),중뇌원위촉액신경원5-HT1A수체표체차이무통계학의의(P＞0.05);여NP+NS조비교,NP+T조중뇌원위촉액신경원5-HT1A수체표체상조,열통역화궤계통역승고(P＜0.05).결론 곡마다가하조중뇌원위촉액신경원5-HT1A수체적표체,해작용가능시기감경대서신경병이성통적궤제지일.
Objective To investigate the effect of tramadol on the expression of 5-HT1A receptor in the distal'cerebrospinal fluid contacting neurons (CSF-CNs) in mid-brain in a rat model of neuropathic pain. Methods Forty male SPF SD rats weighing 220-280 g were randomly divided into 5 groups (n = 8 each): group Ⅰ normal control (group C); group Ⅱ normal saline (group NS); group Ⅲ tramodol (group T); group Ⅳ neuropathic pain + normal saline (group NP+ NS) and group Ⅴ neuropathic pain + tramadol (group NP + T). Neuropathic pain was induced by chronic constrictive injury (CCI) in group Ⅳ and Ⅴ . Four silk ligatures were placed on the sciatic nerve at 1 mm intervals. In group Ⅱ (NS) and group Ⅲ (T) the sciatic nerve was exposed but not ligated and NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively, while in group Ⅳ and Ⅴ NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively on the 7th day after CCI. Paw withdrawal threshold (PWT) to von Frey filament stimulation and paw withdrawal latency (PWL) to noxious thermal stimuli were measured before (T1) and after IP NS or tramadol injection (T2) in group Ⅱ-Ⅴ. The distal CSF-CNs in the mid-brain was labelled with 30% cholera toxin subunit B and horseradish peroxidase compound (CB-HRP) 3 μl injected in left lateral cerebral ventricle. The expression of 5-HT1A receptors was measured by immuno-histochemistry. Results PWT and PWL were significantly decreased after CCI in group Ⅳ (NP + NS) and tramadol significantly inhibited the mechanical and thermal hyperalgesia in group Ⅴ (NP + T). There was no significant difference in the number of distal CSF-CNs among the 5 groups. CCI significantly down-regulated the expression of 5-HT1A in distal CSF-CNs in group Ⅳ(NP+ NS) as compared with group Ⅰ , Ⅱ and Ⅲ and tramadol significantly inhibited the CCI-induced downregulation of 5-HT1A receptor expression. Conclusion Tramadol can ease neuropathic pain by down-regulating the expression of 5-HT1A receptor in distal CSF-CNs in mid-brain.