- Email: [email protected]
Mechanism of inhibitory action of enkephauns, norepinephrine, (-)-baclofen and somatostatin in the spinal dorsal horn: An in vitro study
s171
EFFECT OF OPIOID AND BENZODIAZEPINE AGONISTS AND ANTAGONISTS ON A LATE NEGATIVE COMPONENT (LN) OF THE RAT SOMATOSENSORY EVOKED POTENTIAL (SEP) RELATED TO PAIN. J. ManP*, Ph. Lebrun*, C. Van Laere, Y. Daniel*, M. Vervaeck’, M. Diltoer*, and F. Faculties of Medicine, Free Universities of Brussels (VUB -
BROWN Mon-Tues ACC Hall E Abs No
336
ULB), Laarbeeklaan 103,lWO - Brussels, Belgium. AIM OF INVESTIGATION: The late components of the SEPs are known to be related in man to congnitive processes triggered by the stimulus. These potentials are also known to be exceedingly sensitive to awareness and are readily suppressed by general anaesthetics. On the other end, painful stimuli are particularly potent in evoking strong aversive behavior, in maintaining a high degree of alertness and anxiety, both in man and animals. We found that the amplitude of a late negative wave LN parallels aversive behavior of the rat on painful electrical stimuli. Therefore, it was important to correlate the effect of analgesic and/or anxiolytic drugs on behavior with the amplitude and the latency of this wave. METHODS: Extradural electrodes were implanted over the right hemisphere and the SEPs were recorded after electrical stimulation of the left side of tbe base of the tail at twice the motor threshold every 3 see. Usually 50 to 100 responses were averaged. The SEPs presented an early positivenegative (P-N) complex followed by a late negative wave (LN). The amplitude and latency of the LN wave was evaluated every 2.5 or 5 minutes. The behavior and degree of alertness was also observed and noted. RESULTS: After IM administration of FENTANYL 15 clglkg the LN wave disappeared witbin 5 min and recovered full amplitude after 60 min. Control value was recovered immediately after IM of 1 mg/kg of NALOXONE. After IP administration of MIDAZOLAM 2 mg/kg the latency of the LN wave increased by 25 % and the peak amplitude decreased by 15 46 within about 15 min. The latency returned to normal after 120 min. After IP administration of ALPRAZOLAM 4 mg/kg, a longer acting henzodiaxepine, the same effects were observed within the 5 min and were followed by a complete vanishing of the LN wave. Spontaneous recuperation was achieved only after 3 hours. FLUMAZENIL 4 mg/kg IP reversed these effects almost instantaneously but temporarily. The observed aversive behavior correlated nicely with the modulation of the LN wave. Further more, the time-course of LN wave depression was found to parallel the time course of tail-flick and hot-plate measurements made in the same experimental conditions. CONCLUSION: The strong correlation between behavior and the LN wave of the SEP of the rat suggests a tight link between this wave and awareness, pain, anxiety and aversion. It can be hypothetised that the change in amplitude and latency of the LN wave after drug administration, corresponds to an alterration of the cortical processing of the nociceptive afferent volley. The LN wave may he used as an elcctrophysiological parameter to measure experienced pain and to evaluate analgesic and/or anxiolytic effects of drugs.
MECHANISM OF INHlBlTORYACTlON OF ENKEPHALlNS,NOREPINEPHRINE, (-)-SACLOFEN AND SOMATOSTATlN IN THE SPINAL DORSAL HORN: AN IN WfRoSTlJDY s.JefIbl&and2.Korade.. Dept of vet Anatomy,Iowa state universityJunes, kwa 50011, USA
Poster 30 BROWN Mon-Tues ACC Hall E
Abs No 337 AIM OF INVESTIGATION: This ms a smiu~of qWnants to estWish the sib of inhibkry clelianotopiddr,nonpkwphrire(NE),romdPrtdin(SS),md(-)~~Md bimmigatethe b,I o intamtbnamcmginhWWsdsymapticimnmWanwtmapplied~. MFTHODS: Toshrdy thotmnstarofsmnmyM lromth@EOlWO?YfWWOnb~~hom(DH)fWfOt-l,M kukypqaafbn awmWngafaratapinal~DHallce(400-500umthblfJ with intactdom&roots(DR)mddandmot muronsmabpwkmwdwilh3M ~~D~~fwd. lnWaceWrtwx&ngskimringlcDHneuronandDFlG -havhgDC tw&anceor12&150MQ. Dorumotsmn&nulahdbyuring rlknulrtbn-. Thethlwolds~~~~mdamallunmyrlhdd~ fhwronsandhawbwnfoundtobe8-2lW/k02mrbrthe most sensik axons and OvlK35v/osms fiw C-fibers. RE+lLT% Sath appWtkm a#enk@aHns, NE, and (+badohm p&uasd , in WJition to hyplrrpoluiuaion, ~atexcknytmnsmbsicm in [email protected] neuronsand increasudamdu&mwokwvad rdlowingirwbiwywzvBmwr Secausewrhakekundlhataomenwmns fece@omforoompound8withanthociapthn enlqWintiNEpraducadn~, therewasnoswn~of~~theaompowrdrwnregiven (n=12).0pioidsinbw -tmtions(10_7to 106M) deprwwd tiruponrm bDQll(hwinanY muroneetutal bysf&llksradwbnwitharRrMedingt)w,potlbndthe~~ lqeflbem.NEand(-)-brdodcnpmducad w kinddfkm. decnmetheampMudeanddur&ion of EPSP . CONCLUSIONS; Enkaphalhr, NE, SS and (-)-bnclofenproduad dose dqankt s m witn anincreasein mWlblWWCWiductmce.I ~~~postsynoticW, opkidrrpcMcJlydlprsrr~ C-rian~EPSPbycrctingat~-~~.~p~byNEud(-)-badakn~not~~ smallfiber fesponae. SS, huwewr, acts primarily [email protected] by NIH grant NS27751 ad USDAgIMt.
EFFECT OF OPIOID AND BENZODIAZEPINE AGONISTS AND ANTAGONISTS ON A LATE NEGATIVE COMPONENT (LN) OF THE RAT SOMATOSENSORY EVOKED POTENTIAL (SEP) RELATED TO PAIN. J. ManP*, Ph. Lebrun*, C. Van Laere, Y. Daniel*, M. Vervaeck’, M. Diltoer*, and F. Faculties of Medicine, Free Universities of Brussels (VUB -
BROWN Mon-Tues ACC Hall E Abs No
336
ULB), Laarbeeklaan 103,lWO - Brussels, Belgium. AIM OF INVESTIGATION: The late components of the SEPs are known to be related in man to congnitive processes triggered by the stimulus. These potentials are also known to be exceedingly sensitive to awareness and are readily suppressed by general anaesthetics. On the other end, painful stimuli are particularly potent in evoking strong aversive behavior, in maintaining a high degree of alertness and anxiety, both in man and animals. We found that the amplitude of a late negative wave LN parallels aversive behavior of the rat on painful electrical stimuli. Therefore, it was important to correlate the effect of analgesic and/or anxiolytic drugs on behavior with the amplitude and the latency of this wave. METHODS: Extradural electrodes were implanted over the right hemisphere and the SEPs were recorded after electrical stimulation of the left side of tbe base of the tail at twice the motor threshold every 3 see. Usually 50 to 100 responses were averaged. The SEPs presented an early positivenegative (P-N) complex followed by a late negative wave (LN). The amplitude and latency of the LN wave was evaluated every 2.5 or 5 minutes. The behavior and degree of alertness was also observed and noted. RESULTS: After IM administration of FENTANYL 15 clglkg the LN wave disappeared witbin 5 min and recovered full amplitude after 60 min. Control value was recovered immediately after IM of 1 mg/kg of NALOXONE. After IP administration of MIDAZOLAM 2 mg/kg the latency of the LN wave increased by 25 % and the peak amplitude decreased by 15 46 within about 15 min. The latency returned to normal after 120 min. After IP administration of ALPRAZOLAM 4 mg/kg, a longer acting henzodiaxepine, the same effects were observed within the 5 min and were followed by a complete vanishing of the LN wave. Spontaneous recuperation was achieved only after 3 hours. FLUMAZENIL 4 mg/kg IP reversed these effects almost instantaneously but temporarily. The observed aversive behavior correlated nicely with the modulation of the LN wave. Further more, the time-course of LN wave depression was found to parallel the time course of tail-flick and hot-plate measurements made in the same experimental conditions. CONCLUSION: The strong correlation between behavior and the LN wave of the SEP of the rat suggests a tight link between this wave and awareness, pain, anxiety and aversion. It can be hypothetised that the change in amplitude and latency of the LN wave after drug administration, corresponds to an alterration of the cortical processing of the nociceptive afferent volley. The LN wave may he used as an elcctrophysiological parameter to measure experienced pain and to evaluate analgesic and/or anxiolytic effects of drugs.
MECHANISM OF INHlBlTORYACTlON OF ENKEPHALlNS,NOREPINEPHRINE, (-)-SACLOFEN AND SOMATOSTATlN IN THE SPINAL DORSAL HORN: AN IN WfRoSTlJDY s.JefIbl&and2.Korade.. Dept of vet Anatomy,Iowa state universityJunes, kwa 50011, USA
Poster 30 BROWN Mon-Tues ACC Hall E
Abs No 337 AIM OF INVESTIGATION: This ms a smiu~of qWnants to estWish the sib of inhibkry clelianotopiddr,nonpkwphrire(NE),romdPrtdin(SS),md(-)~~Md bimmigatethe b,I o intamtbnamcmginhWWsdsymapticimnmWanwtmapplied~. MFTHODS: Toshrdy thotmnstarofsmnmyM lromth@EOlWO?YfWWOnb~~hom(DH)fWfOt-l,M kukypqaafbn awmWngafaratapinal~DHallce(400-500umthblfJ with intactdom&roots(DR)mddandmot muronsmabpwkmwdwilh3M ~~D~~fwd. lnWaceWrtwx&ngskimringlcDHneuronandDFlG -havhgDC tw&anceor12&150MQ. Dorumotsmn&nulahdbyuring rlknulrtbn-. Thethlwolds~~~~mdamallunmyrlhdd~ fhwronsandhawbwnfoundtobe8-2lW/k02mrbrthe most sensik axons and OvlK35v/osms fiw C-fibers. RE+lLT% Sath appWtkm a#enk@aHns, NE, and (+badohm p&uasd , in WJition to hyplrrpoluiuaion, ~atexcknytmnsmbsicm in [email protected] neuronsand increasudamdu&mwokwvad rdlowingirwbiwywzvBmwr Secausewrhakekundlhataomenwmns fece@omforoompound8withanthociapthn enlqWintiNEpraducadn~, therewasnoswn~of~~theaompowrdrwnregiven (n=12).0pioidsinbw -tmtions(10_7to 106M) deprwwd tiruponrm bDQll(hwinanY muroneetutal bysf&llksradwbnwitharRrMedingt)w,potlbndthe~~ lqeflbem.NEand(-)-brdodcnpmducad w kinddfkm. decnmetheampMudeanddur&ion of EPSP . CONCLUSIONS; Enkaphalhr, NE, SS and (-)-bnclofenproduad dose dqankt s m witn anincreasein mWlblWWCWiductmce.I ~~~postsynoticW, opkidrrpcMcJlydlprsrr~ C-rian~EPSPbycrctingat~-~~.~p~byNEud(-)-badakn~not~~ smallfiber fesponae. SS, huwewr, acts primarily [email protected] by NIH grant NS27751 ad USDAgIMt.