Effects of morphine and endomorphins on the polysynaptic reflex in the isolated rat spinal cord

Abstract

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.

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics

“…Morphine has been reported to produce consistent inhibitory effects on ventral root responses evoked by C-fiber intensity stimulation of the corresponding dorsal root at concentrations in the nM range [17][18][19][20][21][22]. Similarly, the firing associated to the polysynaptic reflex was maximally reduced by 1 lM morphine [23]. The MSR was mainly unaffected in these studies although small amplitude reductions are reported for high concentration applications of morphine [19][20][21].…”

“…The endogenous opioids Met5‐enkephalin and dynorphin have been shown to reduce the PSR . Other endogenous μ‐opioid ligands, such as endomorphin EM‐2, reduced significantly the C‐fiber‐dependent PSR although EM‐1 was ineffective . Different κ ‐opioid agonists such as enadoline and U69‐593 reduced the PSR applied in the nM range .…”

Flexor myoclonus of the arm due to posttraumatic cervico-thoracic syringomyelia

“…These findings, together with the phenomenology of the myoclonus and its response to methadone, suggest a mechanism involving an intraspinal pathway, susceptible to nociceptive input and endorphin receptor activation. There is evidence from human and animal literature that endogenous and exogenous opioids suppress spinal nociceptive flexion reflexes mainly by acting on spinal mu-opioid receptors [7][8][9]. However, except in patients with restless legs syndrome, respectively periodic limb movements during sleep [10] opioids are not known to decrease involuntary movements of spinal origin.…”