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Spinal serotonin terminal system mediates antinociception
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nucleus caudalis and the subjacent lateral reticular formation are the trigeminal homolog of the spinal dors~ horn. Elevation of pain threshold t o t o o t h s h o c k by brain stimulation in primates. -- T.D. Oleson, D.B. Kirkpatrick and S.J. Goodman, Brain Res., 194 (1980)
79-95 This study demonstrates that escape and titration thresholds to tooth pulp electrical stimulation in monkey are raised following electrical stimulation of certain areas of the primate brain. The most effective sites were in the medial diencephalon with little effect resulting from stimulation of the midbrain central gray. Only moderate effects were produced by stimulation of raphe magnus. These findings are in contrast to results in rat and cat where brain stem sites were very effective in producing "stimulation-produced analgesia". Electrical stimulation of brain stem sites produced vigorous lever pressing responses to terminate the stimulation. Stimulation of diencephalic sites and limbic structures, on the other hand~ elicited .~elf-stimulation responses. The authors conclude that motivational processes as well as the sensory aspects of pain perception are elevated by brain stimulation. Effects o f substance P o n n o c i c e p t i v e and n o n - n o c i c e p t i v e trigeminal brain stem n e u r o n s . - J.L. Henry, B.J. Sessle, G.E. Lucier and J.W. Hu, Pain, 8 (1980) 33--45 The responses of neurons in cat trigeminal brain stem nuclei were examined following the iontophoretic application of glutamate, substance P and opioid peptides. Glutamate excited all neurons tested. Neurons excited by substance P were located only in trigeminal nucleus caudalis and all responded to noxious cutaneous stimuli or tooth pulp stimulation, or both. Neurons activated only by innocuous stimuli were unaffected by substance P. Opioid peptides had depressive effects on nociceptive neurons. These findings support the hypothesis that substance P and endogenous opioids are involved in chemical ~rausmission in nociceptive pathways. Furthermore, the specificity of action of substance P and opioids in nucleus caudalis, and their similar action in the spinal dorsal horn, provide additional evidence that trigeminal nucleus caudalis is the trigeminal homolog of the spinal dorsal horn. PHARMACOLOGY Spinal serotonin terminal system m4~iates antinociception.- T.L. Yaksh and P.R. Wilson, J. Pharmacol. exp. Ther., 208 (1979) 446--453 Rats, rabbits and cats w e r e chronically implanted with catheters in the lumbar spinal subarachnoid space. Serotonin administered through these catheters produced a significant, dose-dependent p.levation in the response of all 3 species to otherwise aversive thermal stimuli. These effects were unaccompanied by any detectable changes in voluntary motor function, although higher doses produced some signs of tremor and a mild myoclonus.
119 The effects of intrathecal serotonin were potentiated by blockade c,f n~onoamine oxidase or reuptake while the effects were antagonized in a surm~untable fashion with methysergide and cyproheptadine. This potentiation and inhibition was observed when the several drugs were administered Jntrathecally suggesting that the observed effects were direct at the spinal level and not indirect via an action on brain stem cell bodies. Intratheca~. administration of 5-hydroxytryptophan produced a delayed antinociceptive effect which was antagonized by methysergide and potentiated by inhibition of monoamine oxidase and reuptake. Inhibition of decarboxylation completely abolished this effect. The effects of intrathecal serotonin were no~ antagonized by papaverine, phenoxybenzamine, phentolamine or naloxone. Collectively, these data suggest that intrathecally administered serotonin mimics the effects produced when descending serotonergic pathways are activated. These data support the proposition that spinal serotonin terminals can modulate spinal function so as to alter the cephalad transmission of nociceptive information.
Antinociceptive activity of clonidine and its potentiation of morphine analgesia. -- T.C. Spaulding, S. Fielding, J.J. Venafro and H. Lal, Europ. J. Pharmacol., 58 (1979) 19--25 The activity of clonidine, a clinically useful antihypertensive agent, and its interaction with morphine was assessed in the mouse tail-flick assay. In this assay, clonidine was found to be 10 times more potent than morphine. Clonidine potentiated morphine antinociceptive activity approximately 5-fold and morphine potentiated clonidine activity 4-fold. Cl,~nidine's agonistic activity was not reversed by naloxone hydrochloride (10 mg/kg) while the potentiating effect of clonidine by morphine was. Tolerance to the antinociceptive effect of morphine was observed in morphine pelletAmplanted mice but no cross-tolerance was observed for clonidine. These data indicate that clonidine-induced analgesia is not a result of an interaction at morphine receptors; but that common pathway(s) are present which appear to complement the agonistic interaction of each. Nociceptor stimulation and PGE release by capsaicin.- H. Juan, F. Lembeck. S. Seewann and U. Hack, Naunyn-Schmiedeberg's Arch. exp. Path. Pharmak., 312 (1980) 139--143 Capsaicin was found to impair selectively, after initial violent stimulation, the function of chemosensitive pain fibers. The present study was aimed at investigating the effects of capsaicin on the isolated perfused rabbit ear connected to the body by its nerve, a preparation that has been extensively used for the study of effects of algesic agents on paravascular nociceptors. Intraarterial injection of capsaicin (threshold dose 0.3/~g) into the isolated perfused rabbit ear causes a dose-dependent reflex fall in blood p~c~;sure by stimulation of chemosensitive nociceptors. Infusion of capsaicin (1 and 10 pg/ml) into the isolated rabbit ear dose-dependently stimulates prostaglandin biosynthesis, equally in innervated and chronically denervated preparations,
nucleus caudalis and the subjacent lateral reticular formation are the trigeminal homolog of the spinal dors~ horn. Elevation of pain threshold t o t o o t h s h o c k by brain stimulation in primates. -- T.D. Oleson, D.B. Kirkpatrick and S.J. Goodman, Brain Res., 194 (1980)
79-95 This study demonstrates that escape and titration thresholds to tooth pulp electrical stimulation in monkey are raised following electrical stimulation of certain areas of the primate brain. The most effective sites were in the medial diencephalon with little effect resulting from stimulation of the midbrain central gray. Only moderate effects were produced by stimulation of raphe magnus. These findings are in contrast to results in rat and cat where brain stem sites were very effective in producing "stimulation-produced analgesia". Electrical stimulation of brain stem sites produced vigorous lever pressing responses to terminate the stimulation. Stimulation of diencephalic sites and limbic structures, on the other hand~ elicited .~elf-stimulation responses. The authors conclude that motivational processes as well as the sensory aspects of pain perception are elevated by brain stimulation. Effects o f substance P o n n o c i c e p t i v e and n o n - n o c i c e p t i v e trigeminal brain stem n e u r o n s . - J.L. Henry, B.J. Sessle, G.E. Lucier and J.W. Hu, Pain, 8 (1980) 33--45 The responses of neurons in cat trigeminal brain stem nuclei were examined following the iontophoretic application of glutamate, substance P and opioid peptides. Glutamate excited all neurons tested. Neurons excited by substance P were located only in trigeminal nucleus caudalis and all responded to noxious cutaneous stimuli or tooth pulp stimulation, or both. Neurons activated only by innocuous stimuli were unaffected by substance P. Opioid peptides had depressive effects on nociceptive neurons. These findings support the hypothesis that substance P and endogenous opioids are involved in chemical ~rausmission in nociceptive pathways. Furthermore, the specificity of action of substance P and opioids in nucleus caudalis, and their similar action in the spinal dorsal horn, provide additional evidence that trigeminal nucleus caudalis is the trigeminal homolog of the spinal dorsal horn. PHARMACOLOGY Spinal serotonin terminal system m4~iates antinociception.- T.L. Yaksh and P.R. Wilson, J. Pharmacol. exp. Ther., 208 (1979) 446--453 Rats, rabbits and cats w e r e chronically implanted with catheters in the lumbar spinal subarachnoid space. Serotonin administered through these catheters produced a significant, dose-dependent p.levation in the response of all 3 species to otherwise aversive thermal stimuli. These effects were unaccompanied by any detectable changes in voluntary motor function, although higher doses produced some signs of tremor and a mild myoclonus.
119 The effects of intrathecal serotonin were potentiated by blockade c,f n~onoamine oxidase or reuptake while the effects were antagonized in a surm~untable fashion with methysergide and cyproheptadine. This potentiation and inhibition was observed when the several drugs were administered Jntrathecally suggesting that the observed effects were direct at the spinal level and not indirect via an action on brain stem cell bodies. Intratheca~. administration of 5-hydroxytryptophan produced a delayed antinociceptive effect which was antagonized by methysergide and potentiated by inhibition of monoamine oxidase and reuptake. Inhibition of decarboxylation completely abolished this effect. The effects of intrathecal serotonin were no~ antagonized by papaverine, phenoxybenzamine, phentolamine or naloxone. Collectively, these data suggest that intrathecally administered serotonin mimics the effects produced when descending serotonergic pathways are activated. These data support the proposition that spinal serotonin terminals can modulate spinal function so as to alter the cephalad transmission of nociceptive information.
Antinociceptive activity of clonidine and its potentiation of morphine analgesia. -- T.C. Spaulding, S. Fielding, J.J. Venafro and H. Lal, Europ. J. Pharmacol., 58 (1979) 19--25 The activity of clonidine, a clinically useful antihypertensive agent, and its interaction with morphine was assessed in the mouse tail-flick assay. In this assay, clonidine was found to be 10 times more potent than morphine. Clonidine potentiated morphine antinociceptive activity approximately 5-fold and morphine potentiated clonidine activity 4-fold. Cl,~nidine's agonistic activity was not reversed by naloxone hydrochloride (10 mg/kg) while the potentiating effect of clonidine by morphine was. Tolerance to the antinociceptive effect of morphine was observed in morphine pelletAmplanted mice but no cross-tolerance was observed for clonidine. These data indicate that clonidine-induced analgesia is not a result of an interaction at morphine receptors; but that common pathway(s) are present which appear to complement the agonistic interaction of each. Nociceptor stimulation and PGE release by capsaicin.- H. Juan, F. Lembeck. S. Seewann and U. Hack, Naunyn-Schmiedeberg's Arch. exp. Path. Pharmak., 312 (1980) 139--143 Capsaicin was found to impair selectively, after initial violent stimulation, the function of chemosensitive pain fibers. The present study was aimed at investigating the effects of capsaicin on the isolated perfused rabbit ear connected to the body by its nerve, a preparation that has been extensively used for the study of effects of algesic agents on paravascular nociceptors. Intraarterial injection of capsaicin (threshold dose 0.3/~g) into the isolated perfused rabbit ear causes a dose-dependent reflex fall in blood p~c~;sure by stimulation of chemosensitive nociceptors. Infusion of capsaicin (1 and 10 pg/ml) into the isolated rabbit ear dose-dependently stimulates prostaglandin biosynthesis, equally in innervated and chronically denervated preparations,