In vivo tonic inhibition of spinal substance P (-like material) release by endogenous opioid(s) acting at δ receptors (original) (raw)

Although numerous data support the existence of a presynaptic inhibitory control by opioids of substance P-containing primary afferent fibres entering the dorsal horn of the spinal cord, the exact nature of the opioid receptor involved in this control is still a matter of debate. In the present study, the potential role of 6 opioid receptors was investigated by looking for the possible effects of selective 6 ligands on the in vivo release of substance P-like material from the whole spinal cord in halothane-anaesthetized rats. Perfusion of the intrathecal space allowed the collection of substance P-like material that was released at a constant rate of ~0.65pg substance P equivalents/min for at least 135 min. The addition of Tyr-o-Thr-Gly-Phe-Leu-Thr (10/tM) or dermenkephalin (10pM), two selective 6 agonists, to the perfusing fluid produced a marked reduction (-50-65%) in substance P-like material outflow which could be prevented by the selective ~ antagonist naltrindole (10 pM) but not by naloxone (10 pM), which acts preferentially on/t opioid receptors. Furthermore, naltrindole alone (or the association of this antagonist plus dermenkephalin) enhanced the outflow of substance P-like material (+ 170%) as expected from the blockade of a tonic inhibitory control due to the stimulation of 6 receptors by endogenous opioids. In contrast, naloxone alone did not modify the spontaneous release of substance P-like material from the spinal cord of halothane-anaesthetized rats, indicating that # opioid receptors are probably not playing an important role in this tonic opioid control of substance P-containing fibres. These data suggest that the antinociceptive effect of ~ agonists injected via the intrathecal route may involve, at least partly, a presynaptic inhibitory control of small diameter substance P-containing primary afferent fibres.

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