Objective It is to investigate the change of melanocortin 4 receptor (MC4R) expression in the periaqueductal gray (PAG) in rats with chronic sciatic nerve compression injury (CCI)and the effect of HS014 (a selective antagonist of MC4R) on the thermal hyperalgesia induced by CCI .Methods 42 healthy male Wistar rats were randomly divided into 3 groups, including the control group (n=6), sham operation group(n=18)and CCI group (n=18).Thermal withdraw laten-cy (TWL) were measured before operation and 3,7,14 d after operation.Rats in the CCI group and sham operation group were killed on postoperative 3,7,14 d after measuring TWL and rats in the control group were killed on postoperative 14 d after measuring TWL, the PAG was taken for detecting the expreesion of MC 4R by using RT-PCR.Another 30 rats were randomly divided into control group (n=6), sham operation group(n=6)and CCI group (n=18), rats in the three groups were all re-ceived PAG cannulation before surgery .7 days after PAG cannulation , rats in CCI group were randomly divided into CCI +NS group,CCI+HS014 5 μg group and CCI+HS014 10μg group (n=6 each),then the sham operation group and CCI group re-ceived operation.14 days after operation, CCI+NS group received PAG injection of 0.5μL normal saline, CCI+HS014 5μg group received PAG injection of HS 014 5 μg/0.5 μL and CCI+HS014 10 μg received PAG injection of HS014 10 μg/0.5μL.TWL were measured at 7 days after PAG cannulation ,14 days after operation and 10~30 min after drug administration . Results The behavior tests showed that TWL started to decrease at 3 days after CCI(P<0.05), and obviously decreased at 7 and 14 days after surgery(P<0.05).It was statistically significant comparing with the corresponding time point of sham group and control group (all P<0.05).RT-PCR analysis revealed that the mRNA expression of MC4R in PAG was significantly higher at each time point in CCI group than that in the sham group and control group (all P<0.05), and the MC4RmRNA expression was gradually increased with time in the CCI group (all P<0.05).TWL was significantly decreased in the whole CCI group after operation compared with 7 days after PAG cannulation(all P<0.05); There was no significant difference in TWL before and after NS treatment in the CCI group (P>0.05).Compared with CCI+NS group and 7 d after PAG cannula-tion group,TWL was significantly prolonged after PAG injection in the CCI +HS014 5μg group and CCI+HS014 10 μg group (all P<0.05) and TWL in the CCI +HS014 10 μg group was more longer than that in the CCI +HS014 5 μg group after PAG injection (P<0.05).Conclusion The present study suggests that damage to peripheral neurons can cause the increased expression of MC4R mRNA in PAG and the selective MC4R inhibitor HS014 can dose dependently reduce the thermal hyperal-gesia induced by CCI , prompting that the increased expression of MC 4R in PAG may be involved in the development and ma-intenance of neuropathic pain induced by the peripheral nervel injury .%目的观察大鼠慢性坐骨神经损伤（ CCI ）后不同时间点中脑导水管周围灰质（PAG）4型黑皮质素受体（MC4R）mRNA表达变化及给予选择性MC4R拮抗剂HS014对CCI大鼠疼痛行为学的影响。方法①将42只健康成年雄性Wistar大鼠随机分为对照组6只、假手术组18只和CCI组18只，检测各组大鼠术前和术后3，7，14 d热缩足潜伏期（TWL），假手术组和CCI组分别于术后3，7，14 d，对照组于术后14 d TWL检测完成后处死大鼠，取PAG脑组织，用半定量RT－PCR法检测PAG脑区MC4R mRNA表达情况。②将30只健康成年雄性Wistar大鼠随机分为对照组6只、假手术组6只和CCI组18只，均先进行PAG置管。置管后7 d，CCI组随机分成CCI＋NS组、CCI＋HS0145μg组和CCI＋HS01410μg组，每组6只。假手术组和CCI各组手术造模。术后7 d，CCI＋NS组经导管注射生理盐水0．5μL，CCI＋HS0145μg组注射HS0145μg／0．5μL，CCI＋HS01410μg组注射HS01410μg／0．5μL。检测各组大鼠置管后7 d、术后7 d和干预后（注射后10～30 min完成检测）TWL。结果 CCI组大鼠术后3 d开始出现TWL缩短（P＜0．05），术后7 d和14 d TWL缩短更加明显（P均＜0．05），与对照组和假手术组比较差异均有统计学意义（P均＜0．05）。 CCI组术后各时间点MC4RmRNA表达量均明显高于对照组和假手术组（P均＜0．05），并且随着CCI术后时间的推移，MC4RmRNA的表达量逐渐增高（P均＜0．05）。 CCI各组大鼠术后7 d TWL明显低于置管后7 d（P均＜0．05）；CCI＋NS组干预后TWL与术后7 d比较差异无统计学意义（P＞0．05），而CCI＋HS0145μg组和CCI＋HS01410μg组干预后TWL均明显长于术后7 d和CCI＋NS组（P均＜0．05），CCI＋HS01410μg组干预后TWL明显长于CCI＋HS0145μg组（P＜0．05）。结论 CCI可引起PAG中MC4RmRNA的表达增加，其选择性拮抗剂HS014可剂量依赖性减轻CCI大鼠的热痛觉过敏，提示PAG中MC4R的表达增加可能参与神经病理性疼痛的形成和维持。
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