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Spinal regulation of nociception: the role of descending serotonergic systems
S96
DORSAL HORN ENKEPHALINS REDUCEDIN HUNANCBRONICPAIN. J.S. Morley,J.B. Miles,R.F. Venn and T.S.C.Williams,Pain Research Institute, Rice Lane,LiverpoolL9 1AE UK.
/Poster 143 1 RED Mon-Tues/ ExhibitHall / Abs No 186 j , 1 ---.-_-.---I
AIM OF INVESTIGATION: To determineif chronicpain involveschanges in spinaltissuelevelsof peptidespresentin nociceptive paths. METHODS: Humanspinalcordswere retrievedwithin24 h. of deathand frozenat -70°C untilanalysis,when they were dissected(-15'C)to providepiecesof left (L.)and right (R.)dorsaland ventralgrey matter,and dorsal,ventraland lateralwhitematter corresponding to lumbar,thoracicand cervicalsegments. Each was weighed,homogenised in 2M aceticacid,and centrifuged.The supernatant was then analysedfor&endorphin, [Met] and [Leulenkephalins (ME,LB), somatostatin and substanceP, usingour mined BPK-RIA procedures(J. Chrom.1987,e, 93-104). RESULTS: Among the cordsretrieved, 13 were from patientswho had sufferedacuteor chronicpain beforedeath. Resultsto be reportedincludeexamplesof changesin dorsal grey NE and LE levelsin two patientswho sufferedchronicpain. Normallevelsat this site were 50-270(ME)and 20-50 (LB)fmol/mgwet tissue. One patient(JF)had 3 monthspain in L. upperarm (C5 distribution); L. levelsof ME and LE at C5 ((1and 1.0, respectively) were considerably reducedas conparedwith normals,whereasR. levelsat C5 (ME 53, LE 191, and both L. and R. levelsat C7 (ME 100 and 105; LE 37 and 28) were normal. The other (MN)had >l year pain in the R. upperarm (C6-T2distribution);at C4-C6levels,L. and R. levelsof ME (15 and 71, and R. levelsof LE 14) were again reducedsubstantially, and the reduction in ME levelswas also seen at T2-T3 (both25). CONCLUSION:In two casesof chronicpain,spinalenkephalin concentrations were significantly reducedat segmentallevelscorresponding to the pain,and at siteswhere primarysensoryafferentsterminate.Theseresultssupportour speculation (DrugDesignand Delivery,1986,I, 47-50)that dorsalhornpeptidelevelschangeduringchronicpain,and that the changeddistribution may initiatetrophicchangesresponsible for alteredgatingof nociceptive input.
Poster 144 SPINAL REGULATION OF NOCICEPTION: THE ROLE OF RED Man-Tues DESCENDING SEROTONERGIC SYSTEMS. ExhibitHal1 ;. "L",","d* O.-G. Berge, P.K. Eide*, O.B. Fasmer, S. Hunskaar, J.H. Rosland and A. Tjnrlsen, Dept. of Physiology, Abs No 187 Universiiy of Bergen, Arstadveien 19, N-5009 Bergen, Norway. __l__l___._l AIM OF INVESTIGATION: In a series of experiments the role of the raphespinal serotonergic systems in regulation of nociception was studied with the aim to reevaluate the hypothesis that these systems exert a tonic inhibition on nociception. METHODS: Rats and mice were used. Nociception was evaluated using the tail flick test, the hot plate test, the formalin test and the behavioral response to substance P injected intrathecally. The function of the 5-HT systems and other systems was manipulated using serotonergic neurotoxins, spinal transection, and 5-HT agonists and antagonist as well as amine reuptake inhibitors and substance P injected systemically and/or intrathecally. RESUJ,TS AND CONCLUSION: The tail skin temperature was an important factor influencing the results of the tail flick test. Manipulations of the function of the 5-HT systems changed tail skin temperature, presumably by altering tail blood flow. When this was corrected for, no tonic descending inhibition mediated via the raphe-spinal 5-HT systems was found. An increase in stimulation of spinal 5-HT receptors induced antinociception. Substance P seemed to regulate the sensitivity of spinal 5-HT receptors. It was concluded that an increase in the activity of descending serotonergic systems may inhibit nociception, however, there is no tonic ’ activity under normal experimental conditions. When the tail flick test is used, tail skin temperature should be recorded and the results adjusted for changes in this temperature.
DORSAL HORN ENKEPHALINS REDUCEDIN HUNANCBRONICPAIN. J.S. Morley,J.B. Miles,R.F. Venn and T.S.C.Williams,Pain Research Institute, Rice Lane,LiverpoolL9 1AE UK.
/Poster 143 1 RED Mon-Tues/ ExhibitHall / Abs No 186 j , 1 ---.-_-.---I
AIM OF INVESTIGATION: To determineif chronicpain involveschanges in spinaltissuelevelsof peptidespresentin nociceptive paths. METHODS: Humanspinalcordswere retrievedwithin24 h. of deathand frozenat -70°C untilanalysis,when they were dissected(-15'C)to providepiecesof left (L.)and right (R.)dorsaland ventralgrey matter,and dorsal,ventraland lateralwhitematter corresponding to lumbar,thoracicand cervicalsegments. Each was weighed,homogenised in 2M aceticacid,and centrifuged.The supernatant was then analysedfor&endorphin, [Met] and [Leulenkephalins (ME,LB), somatostatin and substanceP, usingour mined BPK-RIA procedures(J. Chrom.1987,e, 93-104). RESULTS: Among the cordsretrieved, 13 were from patientswho had sufferedacuteor chronicpain beforedeath. Resultsto be reportedincludeexamplesof changesin dorsal grey NE and LE levelsin two patientswho sufferedchronicpain. Normallevelsat this site were 50-270(ME)and 20-50 (LB)fmol/mgwet tissue. One patient(JF)had 3 monthspain in L. upperarm (C5 distribution); L. levelsof ME and LE at C5 ((1and 1.0, respectively) were considerably reducedas conparedwith normals,whereasR. levelsat C5 (ME 53, LE 191, and both L. and R. levelsat C7 (ME 100 and 105; LE 37 and 28) were normal. The other (MN)had >l year pain in the R. upperarm (C6-T2distribution);at C4-C6levels,L. and R. levelsof ME (15 and 71, and R. levelsof LE 14) were again reducedsubstantially, and the reduction in ME levelswas also seen at T2-T3 (both25). CONCLUSION:In two casesof chronicpain,spinalenkephalin concentrations were significantly reducedat segmentallevelscorresponding to the pain,and at siteswhere primarysensoryafferentsterminate.Theseresultssupportour speculation (DrugDesignand Delivery,1986,I, 47-50)that dorsalhornpeptidelevelschangeduringchronicpain,and that the changeddistribution may initiatetrophicchangesresponsible for alteredgatingof nociceptive input.
Poster 144 SPINAL REGULATION OF NOCICEPTION: THE ROLE OF RED Man-Tues DESCENDING SEROTONERGIC SYSTEMS. ExhibitHal1 ;. "L",","d* O.-G. Berge, P.K. Eide*, O.B. Fasmer, S. Hunskaar, J.H. Rosland and A. Tjnrlsen, Dept. of Physiology, Abs No 187 Universiiy of Bergen, Arstadveien 19, N-5009 Bergen, Norway. __l__l___._l AIM OF INVESTIGATION: In a series of experiments the role of the raphespinal serotonergic systems in regulation of nociception was studied with the aim to reevaluate the hypothesis that these systems exert a tonic inhibition on nociception. METHODS: Rats and mice were used. Nociception was evaluated using the tail flick test, the hot plate test, the formalin test and the behavioral response to substance P injected intrathecally. The function of the 5-HT systems and other systems was manipulated using serotonergic neurotoxins, spinal transection, and 5-HT agonists and antagonist as well as amine reuptake inhibitors and substance P injected systemically and/or intrathecally. RESUJ,TS AND CONCLUSION: The tail skin temperature was an important factor influencing the results of the tail flick test. Manipulations of the function of the 5-HT systems changed tail skin temperature, presumably by altering tail blood flow. When this was corrected for, no tonic descending inhibition mediated via the raphe-spinal 5-HT systems was found. An increase in stimulation of spinal 5-HT receptors induced antinociception. Substance P seemed to regulate the sensitivity of spinal 5-HT receptors. It was concluded that an increase in the activity of descending serotonergic systems may inhibit nociception, however, there is no tonic ’ activity under normal experimental conditions. When the tail flick test is used, tail skin temperature should be recorded and the results adjusted for changes in this temperature.