缰核痛相关神经元对伤害性刺激和吗啡的反应

THE RESPONSES OF PAIN-RELATED NEURONS IN HABENULA TO NOCICEPTIVE STIMULI AND MORPHINE

目的:观察缰核痛相关神经元对经典镇痛药吗啡的反应,了解缰核的痛觉属性。方法:实验在浅麻醉下的成年大鼠进行。通过脑室插管微量注射,或经五管微电极电泳吗啡、纳络酮、八肽胆囊收缩素(CCK-8)等,并记录缰核内痛相关神经元的单位放电。结果:在内侧缰核、外侧缰核记录的痛相关神经元放电,又可分为痛兴奋性神经元和痛抑制性神经元。在缰核微电泳吗啡后,痛兴奋性神经元以抑制反应为主,痛抑制性神经元以兴奋反应为主。微电泳纳洛酮可以翻转吗啡对缰核的作用。在吗啡耐受大鼠腹腔注射吗啡10mg/kg,LHb痛相关神经元表现为镇痛效应的数量远大于MHb痛相关神经元的,表明外侧缰核受吗啡的作用程度高于内侧缰核。对吗啡耐受大鼠脑室注入CCK拮抗剂后,再由腹腔注射吗啡,可减弱对吗啡的耐受程度。反之,在腹腔注射吗啡(10mg/kg)10min后,侧脑室注射CCK-8(15ng/10μl),CCK-8可拮抗吗啡对LHb的镇痛作用,但对MHb的拮抗作用不明显。结论:缰核的痛兴奋性神经元和痛抑制性神经元对伤害性(痛)刺激敏感而不易发生适应。其中外侧缰核神经元对吗啡的敏感性高于内侧缰核神经元。

Aim： To observe the responses of pain-related neurons in habenula to the nociceptive stimuli and classic analgesic morphine for inquiring into its characteristics of pain. Methods： The experiment was proceeded with adult rats under light anesthetized. Through the cannula inserted by operation or the multielectrodes injecting the morphine, naloxone, CCK-8 and etc into lateral cerebro-ventricule or habenula, the unit firings from the neurons of habenula were recorded. Results： The unit firings were recorded from painrelated neurons distributed in MHb or LHb. The pain-related neurons could be differentiated into pain excitatory or pain inhibitory neurons. After the morphine ionophoresed, the main response of the pain excitatory neurons was inhibited, the pain inhibitory neurons were excited. The naloxone ionophoresed could antagonize the analgesic effect of morphine on neurons of habenula. After the morphine injected（10 mg/kg, i. p） into morphine-tolerated rats, the analgesic efficacy of paln-related neurons in LHb was more stronger than in MHb. It showed that the neurons in LHb were suffered from morphine was higher than MHb. After injection of antagonist of CCK-8 into lateral cerebro-ventricle, morphine injected peritoneally could weaken the tolerance level of morphine. Conversely, after injection of morphine（ 10 mg/kg,i, p. ） 10 min, second time injection of CCK-8 （ 15 ng/10 μl） into lateral cerebro-ventricle could antagonize the analgeic action of morphine on the neurons in LHb, but in MHb the antagonized action was not obviously. Conclusion： The excitatory and inhibitory neurons in Hb were sensitive to the nociceptive stimuli and not easy to adapt to it. The sensitivity of the neurons in LHb to morphine was more higher than the neurons in MHb.