Duggan A W, Hall J G, Headley P M
Br J Pharmacol. 1977 Sep;61(1):65-76.
1 In spinal cats anaesthetized with alpha-chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45 degrees C) and innocuous (deflection of hairs) peripheral stimuli.2 Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone.3 Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (>20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing.4 Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically.
在用α-氯醛糖麻醉的脊髓猫中,研究了用微量移液器电泳给药的吗啡和纳洛酮对背角神经元对有害(将皮肤温度升至45摄氏度以上)和无害(毛发偏转)外周刺激反应的影响。
在细胞体附近给药时,吗啡仅降低了37个细胞中2个细胞的伤害性反应。兴奋比抑制更常见,并且在注射吗啡后通常观察到动作电位异常。电泳应用纳洛酮未拮抗吗啡的这些作用。
用一个微量移液器在胶状质中给药,同时用另一个微量移液器记录更深层神经元的反应,吗啡降低了19个神经元中15个神经元的伤害性反应。吗啡未降低对毛发偏转的放电。吗啡对伤害性反应的抑制作用持续时间长(>20分钟)。注入胶状质或静脉注射低至0.1mg/kg剂量的纳洛酮可拮抗吗啡的作用。该剂量静脉注射纳洛酮的有效性表明,降低伤害性反应的胶状质中吗啡浓度与全身给予镇痛剂量吗啡后存在的浓度并无不同。单独的纳洛酮以及注入胶状质的兴奋性和抑制性氨基酸对细胞放电几乎没有影响。
吗啡对伤害性反应的选择性作用以及静脉注射纳洛酮对该作用的逆转表明,胶状质中存在的阿片受体与全身给予阿片类药物产生的镇痛作用有关。