Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord

Abstract

The actions of opioid receptor agonists on synaptic transmission in substantia gelatinosa (SG) neurones in adult (6‐ to 10‐week‐old) rat spinal cord slices were examined by use of the blind whole‐cell patch‐clamp technique. Both the μ‐receptor agonist DAMGO (1 μM) and the δ‐receptor agonist DPDPE (1 μM) reduced the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) which were monosynaptically evoked by stimulating Aδ afferent fibres. Both also decreased the frequency of miniature EPSCs without affecting their amplitude. In contrast, the κ‐receptor agonist U‐69593 (1 μM) had little effect on the evoked and miniature EPSCs. The effects of DAMGO and DPDPE were not seen in the presence of the μ‐receptor antagonist CTAP (1 μM) and the δ‐receptor antagonist naltrindole (1 μM), respectively. Neither DAMGO nor DPDPE at 1 μM affected the responses of SG neurones to bath‐applied AMPA (10 μM). Evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by either the GABAA or the glycine receptor, were unaffected by the μ‐, δ‐ and κ‐receptor agonists. Similar results were also obtained in SG neurones in young adult (3‐ to 4‐week‐old) rat spinal cord slices. These results indicate that opioids suppress excitatory but not inhibitory synaptic transmission, possibly through the activation of μ‐ and δ‐ but not κ‐receptors in adult rat spinal cord SG neurones; these actions are presynaptic in origin. Such an action of opioids may be a possible mechanism for the antinociception produced by their intrathecal administration.

Removing TRPV1-expressing primary afferent neurons potentiates the spinal analgesic effect of δ-opioid agonists on mechano-nociception

“…It has been shown that the release of glutamate and substance P from primary afferent neurons is inhibited by δ-opioid agonists (Glaum et al, 1994;Kohno et al, 1999;Kondo et al, 2005). Thus, the presynaptic action of δ-opioid agonists on nociceptive afferent terminals has been considered an important mechanism underlying the spinal analgesic effect of δ-opioid agonists.…”

“…Spinally administered δ-opioid agonists likely inhibit synaptic transmission through both pre-and postsynaptic mechanisms (Abbadie et al, 2002;Glaum et al, 1994;Kohno et al, 1999;Stewart and Hammond, 1993;Zachariou and Goldstein, 1996). The opioid receptors are coupled to inhibitory G proteins, and voltage-activated Ca 2+ channels are an important downstream signaling target for the opioid analgesic action.…”

“…To ensure that the potentiated analgesic effect of DPDPE in RTX-treated rats was mediated by the δ-opioid receptors, the highly specific δ-opioid receptor antagonist naltrindole (Kohno et al, 1999;Malmberg and Yaksh, 1992) was used. Intrathecal pretreatment with 20 µg naltrindole 15 min before DPDPE administration abolished the antinociceptive effect produced by intrathecal injection of 20 µg of DPDPE in RTX-treated rats (Fig.…”

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

“…However, although cannabinoids and opioids both produce analgesia within the dorsal horn, their pharmacologic mechanisms of action differ. For instance, -opioid receptor agonists inhibit release of glutamate from primary afferent terminals at the level of the spinal and medullary dorsal horn, while CB 1 receptors do not have any inhibitory effect on those excitatory neurons [49,81]. Moreover, -opioid receptors presynaptically inhibit both glycinergic and GABAergic synaptic transmission in the medullary dorsal horn [48], but not in the spinal cord [81], as occurs with CB 1 receptors.…”

“…For instance, -opioid receptor agonists inhibit release of glutamate from primary afferent terminals at the level of the spinal and medullary dorsal horn, while CB 1 receptors do not have any inhibitory effect on those excitatory neurons [49,81]. Moreover, -opioid receptors presynaptically inhibit both glycinergic and GABAergic synaptic transmission in the medullary dorsal horn [48], but not in the spinal cord [81], as occurs with CB 1 receptors. There are other differences at the supraspinal level, where both cannabinoid and opioid recep-tors presynaptically inhibit GABAergic synaptic transmission, disinhibiting nociceptive descending projection neurons, but only -opioid receptors directly inhibit putative GABAergic neurons in the PAG and RVM [19,162,163].…”