Abstract
At the spinal level, μ-opioids exert their actions on nociceptive primary afferent neurons both pre- and postsynaptically. In the present study, we used an in vitro isolated neonatal rat (11–15 days old) spinal cord preparation to examine the effects of morphine and the endogenous μ-opioid ligands endomorphin-1 (EM-1) and endomorphin-2 (EM-2) on the polysynaptic reflex (PSR) of dorsal root-ventral root (DR-VR) reflex. The actions of μ-opioids on spinal nociception were investigated by quantification of the firing frequency and the mean amplitude of the PSR evoked by stimuli with 20×threshold intensity. EM-1 decreased the mean amplitude of PSR, whereas EM-2 and morphine decreased the firing frequency. The pattern of the effects elicited by morphine was the same as that for EM-2, except at high concentration. Naloxonazine, a selective μ1 opioid receptor antagonist, had no significant effect on PSR by itself, but blocked the inhibition of PSR firing frequency or amplitude induced by EM-1, -2 and morphine. This may suggest that EM-1, EM-2 and morphine modulate spinal nociception differently and act mainly at the μ1-opioid receptors. Although they all act via μ1-opioid receptors, their different effects on the PSR may suggest the existence of different subtypes of the μ1-opioid receptor. The present data is also consistent with a further hypothesis, namely, that morphine and EM-2 activate a subtype of μ1-opioid receptor presynaptically, while EM-1 acts mainly through another subtype postsynaptically. However, since other reports indicate that EM-2, but not EM-1, could stimulate the release of enkephalins or dynorphin, presynaptic δ and κ receptors may be also involved indirectly in the different regulation by μ-opioids at the spinal level.
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This study was supported by the grants from the National Health Research Institutes (NHRI-EX93-8909BP) and the National Science Council (NSC 92-2320-B-016-016), Taipei, Taiwan, R.O.C.
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Tao, PL., Lai, YS., Chow, LH. et al. Effects of morphine and endomorphins on the polysynaptic reflex in the isolated rat spinal cord. Naunyn-Schmiedeberg's Arch Pharmacol 371, 72–80 (2005). https://doi.org/10.1007/s00210-004-1004-8
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DOI: https://doi.org/10.1007/s00210-004-1004-8