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Kappa-opioid receptor stimulation abolishes mu- but not delta-mediated inhibitory control of spinal Met-enkephalin
E Collin1, S Bourgoin, L Ferhat
1INSERM U 288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Abstract:
The possible opioid control through delta, mu and kappa receptors of the spinal release of Met-enkephalin-like material (MELM) was investigated in halothane-anaesthetized rats. The intrathecal perfusion of the delta agonist DTLET (10 microM) or the mu agonist DAGO (10 microM) resulted in a marked inhibition of MELM release, which could be prevented by the selective antagonists naltrindole and naloxone, respectively. Although the kappa agonist U 50488 H (10 microM) was inactive per se, it completely suppressed the inhibitory effect of DAGO, without affecting that of DTLET. As the selective kappa antagonist norbinaltorphimine blocked the action of U 50488 H, it can be concluded that kappa receptors modulate the mu- (but not the delta-) mediated feed back control of spinal enkephalinergic neurones.
Insights
Opioid receptors in the spinal cord control pain. Delta and mu agonists inhibit Met-enkephalin-like material (MELM) release, while kappa receptors modulate mu-mediated, but not delta-mediated, control.
Area of Science:
- Neuroscience
- Pharmacology
- Spinal Cord Research
Background:
- Opioid receptors (delta, mu, kappa) play a role in pain modulation.
- Met-enkephalin-like material (MELM) is involved in spinal pain pathways.
- Understanding receptor interactions is crucial for developing analgesics.
Purpose of the Study:
- To investigate the role of delta, mu, and kappa opioid receptors in controlling spinal MELM release.
- To elucidate the modulatory effects of kappa receptors on mu- and delta-mediated inhibition of MELM release.
Main Methods:
- Intrathecal perfusion of specific opioid agonists (DTLET, DAGO, U 50488 H) and antagonists (naltrindole, naloxone, norbinaltorphimine) in halothane-anesthetized rats.
- Measurement of spinal MELM release.
- Assessment of receptor-mediated effects and their modulation.
Main Results:
- Intrathecal DTLET (delta agonist) and DAGO (mu agonist) significantly inhibited MELM release.
- Naltrindole and naloxone blocked the inhibitory effects of DTLET and DAGO, respectively.
- The kappa agonist U 50488 H suppressed the DAGO-induced inhibition but not the DTLET-induced inhibition.
- Norbinaltorphimine (kappa antagonist) blocked the action of U 50488 H.
Conclusions:
- Delta and mu opioid receptors mediate spinal control of MELM release.
- Kappa opioid receptors modulate the mu-mediated, but not the delta-mediated, feedback control of spinal enkephalinergic neurons.
- These findings offer insights into the complex interplay of opioid receptors in spinal pain pathways.
