Kelly S J, Franklin K B
Neuropharmacology. 1985 Nov;24(11):1019-25. doi: 10.1016/0028-3908(85)90185-6.
The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but not by valine and tryptophan (100 mg/kg, i.p.), was taken to indicate that an increase in the uptake of tryptophan in brain was involved in opioid-induced analgesia. Morphine-induced analgesia exhibited by rats that were habituated to the laboratory and not restrained did not involve an increase in the uptake of tryptophan in brain. However, a mild form of restraint, or exposure to a novel environment interacted with morphine to induce analgesia which involved an increase in the uptake of tryptophan in brain. These stressors did not affect sensitivity to pain in the absence of morphine. Analgesia induced by 3 hr of restraint, which was preventable by naltrexone (1 mg/kg, s.c.) but not reversible by naloxone (1 mg/kg, s.c.), also involved an increase in the uptake of tryptophan in brain. It is concluded that the endogenous opioid-induced analgesia that is induced by stress alone and analgesia induced by stress interacting with morphine, both depend on an increase in the uptake of tryptophan into the brain.
通过注射竞争性氨基酸来改变大脑中氨基酸的摄取，研究了应激诱导的大脑中色氨酸摄取增加在阿片类药物诱导的镇痛中的作用。单独使用缬氨酸（200毫克/千克，腹腔注射）以及缬氨酸和酪氨酸（100毫克/千克，腹腔注射）可阻断镇痛作用，但缬氨酸和色氨酸（100毫克/千克，腹腔注射）则不能，这表明大脑中色氨酸摄取增加与阿片类药物诱导的镇痛有关。习惯了实验室环境且未受束缚的大鼠所表现出的吗啡诱导的镇痛作用，并不涉及大脑中色氨酸摄取的增加。然而，轻度束缚或暴露于新环境与吗啡相互作用可诱导镇痛，这涉及大脑中色氨酸摄取的增加。在没有吗啡的情况下，这些应激源不会影响对疼痛的敏感性。由3小时束缚诱导的镇痛作用可被纳曲酮（1毫克/千克，皮下注射）预防，但不能被纳洛酮（1毫克/千克，皮下注射）逆转，这也涉及大脑中色氨酸摄取的增加。结论是，单独由应激诱导的内源性阿片类药物诱导的镇痛作用以及应激与吗啡相互作用诱导的镇痛作用，均依赖于大脑中色氨酸摄取的增加。
