Laurido C, Hernandez A, Perez H
Department of Biological Sciences, Faculty of Chemistry and Biology, University of Santiago of Chile, Chile.
Int J Neurosci. 1996 Nov;87(3-4):191-9. doi: 10.3109/00207459609070837.
Development of tolerance and cross-tolerance after acute administration of the mu agonist morphine and the kappa agonist U-50,488H was assessed in rats, through recording of a C-fiber-evoked spinal nociceptive reflex. Rats rendered tolerant to morphine (a single dose of 1 mg/kg i.p.) showed, after a 5-hour period, tolerance to morphine and cross-tolerance to the kappa-opioid receptor agonist U-50,488H, as revealed by depressed C-reflex responsiveness. In contrast, pretreatment with U-50,488H (a single dose of 1 mg/kg i.p.) rendered tolerant the rats to U-50,488H, but the animals did not develop cross-tolerance to morphine. Results indicate that acute administration of mu and kappa ligands leads to development of unidirectional cross-tolerance in rat spinal cord. This points to limitations in using alternated mu and kappa opioid agonists to bypass the problem of development of opioid tolerance in chronic pain complaints.
通过记录C纤维诱发的脊髓伤害性反射，评估了在大鼠急性给予μ阿片受体激动剂吗啡和κ阿片受体激动剂U-50,488H后耐受性和交叉耐受性的发展情况。对吗啡产生耐受性的大鼠（腹腔注射单剂量1mg/kg）在5小时后，对吗啡表现出耐受性，对κ阿片受体激动剂U-50,488H表现出交叉耐受性，这通过C反射反应性降低得以揭示。相比之下，用U-50,488H（腹腔注射单剂量1mg/kg）预处理使大鼠对U-50,488H产生耐受性，但这些动物对吗啡未产生交叉耐受性。结果表明，急性给予μ和κ配体导致大鼠脊髓单向交叉耐受性的发展。这表明在慢性疼痛患者中，交替使用μ和κ阿片类激动剂以绕过阿片类耐受性发展问题存在局限性。
