Participation of opiate and serotonergic systems in brain conditioning stimulatory inhibition of the potentials evoked by tooth pulp stimulation in the pars caudalis of the trigeminal sensory nucleus of the rat.

Effects of conditioning stimulations of the nucleus raphe magnus (NRM), nucleus reticularis paragigantocellularis (NRPG), mesencephalic periaqueductal central gray (PAG), nucleus dorsomedialis hypothalami (DMH), corpus striatum (CP), sensory cortex (SCT) and visual cortex (VCT) and actions of morphine, naloxone and metergoline on the potentials recorded from the pars caudalis of the trigeminal sensory nucleus evoked by the electrical stimulation of rat incisor pulps were examined. The spinal potentials evoked by electrical stimulation of the pulp consisted of 3 components. Component 2 was mainly inhibited by morphine and antagonized by naloxone. Conditioning stimulation of NRM, NRPG, PAG, CP, SCT and DMH strongly inhibited component 2. VCT did not show any inhibition. 33-67% of antagonism was observed by naloxone in the NRM, NRPG, PAG, CP, SCT and DMH. On the other hand, 27-44% of antagonism was observed by metergoline, and the antagonism was not enhanced by the additional administration of naloxone. These results conclusively show that the endorphin system as well as the serotonergic system is in the series involved in the descending inhibition for nociception in the trigeminal sensory nucleus.

Neurotransmitter modulation of VIP release from cat cerebral cortex.

The cortical release of vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) in vivo was examined by superfusion of the pial surface of the cerebral cortex of the cat. The modulation of cortical VIP release by several neurotransmitters [gamma-aminobutyric acid (GABA), opioids, norepinephrine, acetylcholine, and glutamate] normally present in the cerebral cortex was studied by administering respective agonists and antagonists for their receptors. Although GABA and opiate agonists did not influence the resting release of VIP-LI, GABA antagonists (picrotoxin and bicuculline) and opiate antagonists (naloxone and naltrexone) significantly elevated the resting release. The evoked release from cortex of VIP-LI (by electrical stimulation of the cortex or mesencephalic reticular formation) was suppressed by GABA and mu- but not delta-, kappa-, or sigma-opioid receptor agonists. Glutamate and kainic acid increased the resting release of VIP-LI from the cerebral cortex. Noradrenergic (alpha 2 but not alpha 1) displayed an inhibitory effect on the evoked release of cortical VIP-LI release. Resting VIP-LI release was enhanced by cholinergic agents (carbachol). The facilitatory effects of mesencephalic reticular formation stimulation on VIP-LI release were demonstrated by atropine. These observations suggest characteristic interactions reflecting the circuitry modulating the activity of cortical VIP-releasing neurons.

The nature of opioid involvement in the hemodynamic respiratory and humoral responses to exercise.

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

Opioid systems and feeding in the slug, Limax maximus: similarities to and implications for mammalian feeding.

Substantial evidence is accumulating to implicate opioid systems in the regulation of behavioral and physiological functions in invertebrates in a manner analogous to that observed in vertebrates. This communication reviews opiate involvement in the mediation of the ingestive behaviors of the terrestrial slug, Limax maximus. The similarities to and implications for opioid modulation of mammalian feeding are considered.

Clinical pharmacology of opioid analgesics.

Opioid analgesics continue to be the most important drugs in modifying the response to pain. Their versatility is attested by their frequent use in both postoperative and intraoperative management of pain. Recent findings regarding the mechanism of action of opioids may signal the introduction of newer, more effective, and less addictive agents. So far, this has not occurred. However, opioids with mixed agonist-antagonist properties have offered some utility. The adverse effects of nausea and dysphoria and the more serious effects of respiratory depression continue to be a problem, as does the possibility of abuse. Nonetheless, the clinical experience with opioids in control of pain is uncontested. Until better drugs are developed, opioids will form the basis for the control of acute pain by the dental practitioner.

Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.