Morphine Administered in the Substantia Gelatinosa of the Spinal Trigeminal Nucleus Caudalis Inhibits Nociceptive Activities in the Spinal Trigeminal Nucleus Oralis

Abstract

The present study investigates the effects of morphine microinjection into the spinal trigeminal nucleus caudalis (Sp5C) or the spinal trigeminal nucleus oralis (Sp5O) on C-fiber-evoked activities of Sp5O convergent neurons, after supramaximal percutaneous electrical stimulation in halothane-anesthetized rats. When it was microinjected into the Sp5O, morphine (2.5 microg in 0. 25 microl) never depressed the C-fiber-evoked responses of Sp5O convergent neurons (n = 13), whereas these neurons were responsive to the inhibitory effects of systemic morphine (6 mg/kg, i.v.) in a naloxone-reversible manner. On the contrary, morphine microinjected into the Sp5C produced a naloxone-reversible inhibition of the C-fiber-evoked responses of Sp5O neurons (n = 14). The magnitude and the time course of this effect varied according to the location of the injection sites. After microinjection into the superficial laminae (n = 7), a strong depressive effect of morphine (7 +/- 5% of control) on the C-fiber-evoked responses was apparent as soon as 5 min after the injection and could always be reversed by naloxone, administered either intravenously (0.4 mg/kg) or locally (2.5 microg in 0.6 microl) at the same site as morphine. After microinjection into deeper laminae (V-VI), a significant depressive effect (34 +/- 5% of control) of morphine could be detected only 20 min after the injection and was reversed only by intravenous administration of naloxone. These results suggest that morphine exerts its antinociceptive action on Sp5O convergent neurons by blocking the C-fiber inputs that relay in the Sp5C substantia gelatinosa. The mechanisms that underlie the activation of Sp5O convergent neurons by C-fibers and the inhibition of C-fiber-evoked responses of Sp5O convergent neurons by morphine microinjected into the Sp5C are discussed.

Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia

“…Drugs were delivered in the MDH by two-barrel glass micropipettes (3GC120F-15; Clark Electromedical Instruments) fixed on the micromanipulator and connected to two Hamilton syringes (1 l) by means of polyethylene tubing (Dallel et al, 1998). The micropipette was broken back maximally to a diameter of 70 -100 m. The micropipettes and tubing were filled with GABA A antagonist bicuculline methiodide (50 mol in 0.5 l aCSF) or aCSF with pontamine sky blue, respectively (for location of the injection site).…”

Acute and Chronic Craniofacial Pain: Brainstem Mechanisms of Nociceptive Transmission and Neuroplasticity, and Their Clinical Correlates

“…In support of this possibility are the observations that nociceptive neurons contributing to nociceptive behavior occur in some spinal cord and brainstem areas devoid of some of these substrates (e.g., lateral cervical nucleus, reticular formation) (Dubner and Bennett, 1983 MK-801 (see Section III), may depend on the well-documented ascending projection from subnucleus caudalis that exerts a net facilitatory modulatory influence on oralis neurons (for review, see Sessle, 1987Sessle, , 1996, since the caudalis does have the features (NMDA receptors, Cfiber afferent terminals, substantia gelatinosa) considered necessary for these nociceptive phenomena. Furthermore, local application of MK-801 (Woda et al, 1998) or morphine (Dallel et al, 1998) to subnucleus caudalis can block the C-fiber-related activity of some oralis nociceptive neurons. An analogous argument has also been used as an explanation for the neuroplastic changes that have been documented in subnucleus oralis, and in the main sensory nucleus, subsequent to C-fiber depletion induced by the neonatal application of capsaicin (Kwan et al, 1996.…”

“…The responses to cutaneous C-fiber stimulation, including so-called "wind-up", of nociceptive oralis neurons can be antagonized by systemic morphine in a dosedependent, naloxone-reversible manner (Dallel et al, 1996). These effects could be explained by an opioidmodulated ascending influence from the subnucleus caudalis, since morphine injected into subnucleus caun3 dalis produces a naloxone-reversible depression of the nociceptive activity of oralis neurons (Dallel et al, 1998). Another possible explanation could be opioid-related mechanisms within subnucleus oralis itself, since, according to the literature cited above, it does manifest some opioid-containing terminals and opiate receptors.…”

Neurobiologie de la douleur trigéminale

“…À l'opposé, ces réponses sont sous l'influence de contrôles inhibiteurs descendants [10]. Sur le plan pharmacologique, elles sont inhibées de façon réversible par la naloxone, par l'injection intraveineuse de morphine [15], et majorées par le blocage des récepteurs glycinergiques [16]. Enfin, le windup des neurones à convergence du sousnoyau oral dépend en partie de l'activation des récepteurs du glutamate de type NMDA [17] et des récepteurs de la substance P de type NK1 [18].…”

“…Sous-noyau oral et couche V présentent égale- [22]. Alors que la morphine n'a pas d'effet direct sur les réponses des neurones du sous-noyau oral [15] ou de la couche V lors de la stimulation des fibres C, elle inhibe ces mêmes réponses lorsqu'elle est injectée dans les couches superficielles correspondantes du sous-noyau caudal ou de la corne dorsale de la moelle épinière (Figure 3). En accord avec ces données, l'inhibition pharmacologique [23] ou la lésion [11] du sousnoyau caudal inhibe de façon préférentielle les réponses comportementales toniques dues à l'activation des fibres C, sans modifier les réponses phasiques sous-tendues par la mise en jeu des fibres Aδ.…”