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Pharmacological modulation of pressor and visceromotor responses to colorectal distension (CRD) in the rat
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PHARMACOLOGICAL MODULATION OF PRESSOR AND VISCEROMOTOR RESPONSES TO COLORECTAL DISTENSION (CRD) IN THE RAT. R.M. Danzebrink and G.F. Gebhart, Department of Pharmacology, The University of Iowa, Iowa City, Iowa, 52242
BLACKMon-Tues
AIM OF INVESTIGATION: The antinociceptive efficacy of adrenoceptor 1-1 and serotonin receptor agonists were evaluated in the CRD model of visceral pain. Using air inflation of a latex balloon nonsurgically placed in the descending METHODS: colon and rectum of awake rats (Ness and Gebhart, Brain Res. *153-169, 19881, pressor and visceromotor responses to CRD were monitored before and after intrathecal administration of receptor selective drugs. RFSULTS: Antinociception was produced following the adminstration of a2-, but not al- or S-adrenoceptor agonists. The rank order of potencies to produce inhibition of responses to CRD was: clonidine > NE > ST-91 > tizanidine> isoproterenol= methoxamine= 0. Serotonin receptor agonists for the 5-HT-lA, -lB, -2, and -3 receptor subtypes each produced significant antinociceptive effects, the rank order of potencies being: DO1 > 8-OH-DPAT > MK-212 > RU-24969 > a-methyl-5-HT > 2-methyl-5-HT > > 5-HT. Concomitant administration of an a2-adrenoceptor agonist with a serotonin receptor agonist resulted in dose-dependent supra-additive antinociceptive effects. Spinal adrenoceptors and serotonin receptors mediate antinociception in CONCLUSION: response to noxious visceral stimulation, suggesting that descending bulbospinal neurons are important in the modulation of visceral nociception. That a supra-additive antinociceptive effect results from the coadministration of a2-adrenoceptor and 5-HT receptor agonists suggests a functionally important interaction between these two neuronal systems.
SUBSTANCE-P AND SOMATOSTATIN SPINAL FLUID CONTENT IN PATIENTS WITH
CANCER PAIN. lINnUENCE OF 2PINAL OPIA$E THERAPY. H $amuelsson* , J Lindqvist , R Ekman* and T Hedner3. Departments of1 Anesthesia,Central Hospital Ho&s, 2Neurochemistry,Univ. of Lund and of 3Clin Pharmacology, Sahlgrens Univ. Hospital, Gijteborg, Sweden.
BLACKMon-Tues
AIM OF INVESTIGATION: This study evaluate the cerebrospinalfluid (CSF) content of Substance-P(SP) and Somatostatin(SOM) like imnunoreactivity (SPLI, SOMLI) in 10 controls,free from pain, and 10 patients with severe pain due to malignancy,before and after initiationof spinal opiate (SO) therapy. METHODS: Controls and study group were similar in age, sex and height but nzeight and medication.The study group had oral opiate medication when included in the study. Pain intensitywas evaluated by means of a visual analog scale WAS). Mean VAS was reduced from 6.6 to 2.0 after introductionof SO. 12 ml SF wqe collectedat the b2-L4 interspace, placed in ice, centrifugedat +4 C and stored at -70 C until analysed by specific radioimmunoassay (RIA). RESULTS: There was no significantdifferencein SPLI or SOMLI between the two groups. A slight, but non significant(p=O.O64) decrease in SPLI were detected after initiationof SO. Visceral pain (n=3) was associatedwith low SPLI. No correlationwas seen between SPLI or SOMLI and pain intensity level. Nor was the reduction in pain intensityrelated to any significant changes in neuropeptideconcentrations. CONCLUSION:The result did not support the hypothesis that nociceptive pain is associatedwith increasedSPLI in CSF. Visceral pain may give a decrease. SPLI tended to be reduced in CSF after SO in agreementwith experimentaldata in cat. The pain state was not associatedwith any significantchanges in SOMLI, nor was the introductionof SO.
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PHARMACOLOGICAL MODULATION OF PRESSOR AND VISCEROMOTOR RESPONSES TO COLORECTAL DISTENSION (CRD) IN THE RAT. R.M. Danzebrink and G.F. Gebhart, Department of Pharmacology, The University of Iowa, Iowa City, Iowa, 52242
BLACKMon-Tues
AIM OF INVESTIGATION: The antinociceptive efficacy of adrenoceptor 1-1 and serotonin receptor agonists were evaluated in the CRD model of visceral pain. Using air inflation of a latex balloon nonsurgically placed in the descending METHODS: colon and rectum of awake rats (Ness and Gebhart, Brain Res. *153-169, 19881, pressor and visceromotor responses to CRD were monitored before and after intrathecal administration of receptor selective drugs. RFSULTS: Antinociception was produced following the adminstration of a2-, but not al- or S-adrenoceptor agonists. The rank order of potencies to produce inhibition of responses to CRD was: clonidine > NE > ST-91 > tizanidine> isoproterenol= methoxamine= 0. Serotonin receptor agonists for the 5-HT-lA, -lB, -2, and -3 receptor subtypes each produced significant antinociceptive effects, the rank order of potencies being: DO1 > 8-OH-DPAT > MK-212 > RU-24969 > a-methyl-5-HT > 2-methyl-5-HT > > 5-HT. Concomitant administration of an a2-adrenoceptor agonist with a serotonin receptor agonist resulted in dose-dependent supra-additive antinociceptive effects. Spinal adrenoceptors and serotonin receptors mediate antinociception in CONCLUSION: response to noxious visceral stimulation, suggesting that descending bulbospinal neurons are important in the modulation of visceral nociception. That a supra-additive antinociceptive effect results from the coadministration of a2-adrenoceptor and 5-HT receptor agonists suggests a functionally important interaction between these two neuronal systems.
SUBSTANCE-P AND SOMATOSTATIN SPINAL FLUID CONTENT IN PATIENTS WITH
CANCER PAIN. lINnUENCE OF 2PINAL OPIA$E THERAPY. H $amuelsson* , J Lindqvist , R Ekman* and T Hedner3. Departments of1 Anesthesia,Central Hospital Ho&s, 2Neurochemistry,Univ. of Lund and of 3Clin Pharmacology, Sahlgrens Univ. Hospital, Gijteborg, Sweden.
BLACKMon-Tues
AIM OF INVESTIGATION: This study evaluate the cerebrospinalfluid (CSF) content of Substance-P(SP) and Somatostatin(SOM) like imnunoreactivity (SPLI, SOMLI) in 10 controls,free from pain, and 10 patients with severe pain due to malignancy,before and after initiationof spinal opiate (SO) therapy. METHODS: Controls and study group were similar in age, sex and height but nzeight and medication.The study group had oral opiate medication when included in the study. Pain intensitywas evaluated by means of a visual analog scale WAS). Mean VAS was reduced from 6.6 to 2.0 after introductionof SO. 12 ml SF wqe collectedat the b2-L4 interspace, placed in ice, centrifugedat +4 C and stored at -70 C until analysed by specific radioimmunoassay (RIA). RESULTS: There was no significantdifferencein SPLI or SOMLI between the two groups. A slight, but non significant(p=O.O64) decrease in SPLI were detected after initiationof SO. Visceral pain (n=3) was associatedwith low SPLI. No correlationwas seen between SPLI or SOMLI and pain intensity level. Nor was the reduction in pain intensityrelated to any significant changes in neuropeptideconcentrations. CONCLUSION:The result did not support the hypothesis that nociceptive pain is associatedwith increasedSPLI in CSF. Visceral pain may give a decrease. SPLI tended to be reduced in CSF after SO in agreementwith experimentaldata in cat. The pain state was not associatedwith any significantchanges in SOMLI, nor was the introductionof SO.
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