Effects of morphine and endomorphins on the polysynaptic reflex in the isolated rat spinal cord.
At the spinal level, mu-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 mu-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 mu-opioids on spinal nociception were investigated by quantification of the firing frequency and the mean amplitude of the PSR evoked by stimuli with 20 x 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 mu(1) 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 mu(1)-opioid receptors. Although they all act via mu(1)-opioid receptors, their different effects on the PSR may suggest the existence of different subtypes of the mu(1)-opioid receptor. The present data is also consistent with a further hypothesis, namely, that morphine and EM-2 activate a subtype of mu(1)-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 delta and kappa receptors may be also involved indirectly in the different regulation by mu-opioids at the spinal level.
Tao
Pao-Luh
PL
Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504, Nei-Hu 104, Taipei, Taiwan, Republic of China.
Lai
Yong-Shang
YS
Chow
Lok-Hi
LH
Huang
Eagle Yi-Kung
EY
D000701:Analgesics, Opioid / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D004723:Endorphins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009020:Morphine / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D009842:Oligopeptides / Q000134:cerebrospinal fluid / Q000138:chemical synthesis / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017450:Receptors, Opioid, mu / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
D000701:Analgesics, Opioid; D004723:Endorphins; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2; D009020:Morphine
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