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Circuitry uniking opiate-sensitive nociceptive modulatory systems in rostral ventromedial medulla, perlaoueductal gray and spinal cord
THE INTERPEDUNCULAR NUCLEUS EXCITES ON-CELLS AND IN IBITS OFF-CELL IN THE NUCLEUS RAPHE MAGNUS. I.D. HentalkH and v. Budhranis* 1Biomedical Sciences Dept., Univ. of Illinois ollege of'Medicine at Rockford, Rockford IL 61107, USA, and !? Physiology Dept., Univ. of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico 00936.
Poster 54 BROWN Th-Fri ACC
Hall
Abs No
BIM OF INVESTIGATION : The interpeduncular nucleus (IPN)--a little midbrain area with cholinergic input--may affect pain. IPN lesions learning of avoidance behaviour, and during anaesthesia the IPN is metabolically active. An IPN influence on the nucleus raphe magnus predicted.
E
858
studied impede unusually is
METHODS: Rats (300g) were anaesthetised with pentobarbital, placed in a stereotaxic head holder. A metal recording microelectrode was put in the NRM, and an electrically insulated 27g needle put in the IPN--for both drug delivery and electrical stimulation. Postmortem histology confirmed electrode positions. Drugs used were acetylcholine (ACh), glutamate (Glu), and g-aminobutyric acid (GABA), each 50 mM in 0.5-1~1 injected for 30s. NRM cells were classified as on-, off-, and neutral, as per their RESULTS response to noxious electrical or mechanical stimulation of the hindpaw skin. ACR, Glu, and electrical stimulation in the IPN mainly inhibited (never excited) off-cells and mainly excited (never inhibited) on-cells. Neutral cells were not studied. If, as previous work suggests, on-cell activity causes wperalgesia and off-cell activity analgesia, then IPN output to the NRM should be hyperalgetic, probably via a synapse in the dorsal raphe.
CIRCUITRY UNKING OPlATE-SENStTlVE NOCICEPTIVE MODULATORY SYSTEMS IN ROSTRAL WNTROMEDtAL MEDULlA , FERWUEDUCTAL GRAY AND SPtNAL CORD. j&M, / . . Helnncher. M.M.Morgan and H.L. Fields. Dept. Neurology, ,Unlversity of California, San Francisco, CA 94143
ACC Hall Abs No
859
E
1
J AIM OF INVESTIGATION: On-cells are a class of putative noclceptive modulating neurons identified in the rostra1 ventromedial medulla (RVM) of the barbiturate-anesthetized rat that are thought to exert a permissive, or even facttitatory, role in descending modulation of nocicepttve transmission. Morphine, when given in doses sufficient to inhibit nocifenslve reffexes, reliably suppresses the spontaneous and nocifensor-reflex related firing of RVM on-cells. Suppression of on-cell activity is observed whether morphine is given systemically, into the intrathecal space, or microinjected into the midbrain pertaqueductal gray (PAG). The present experiments used direct activation of on-cells with iontophoretically-apptted iglutamate as an indication of whether morphine-induced suppression of on-cell firing reflected a postsynaptic inhibition, or a dlsfacititatlon resulting from blockade of an excitatory element among the afferents to the on-cell. METHODS: Rats were maintained in a lightly-anesthetized state by a continuous infusion of methohexitai. Physiologically characterized on-ceils were excited by iontophoreticalty-apptiid pulses of i-glutamate (ZO90 nA, 10 s pulse every 20 s). The tail-flick (TF) response to noxious heat was evoked at 5 min intervals in order to verify the antinociceptive effect of morphine given systemically (1.255 mg/kg), intrathecally (lo-15 ug), or by microinjection in the PAG (7.515 ug). RESULTS: Following either systemic or PAG administration of morphine, glutamate-evoked firing of onceils was suppressed along with spontaneous activity and the TF response. Intrathecally-administered morphine sufficient to block the TF did not depress glutamate-evoked firing, even though spontaneous and TFrelated activity were completely suppressed. CONCLUSIONS: These obsenratlons provide positive evidence that administration of morphine either systemically or by microinjection in the PAG causes an inhibition of on-ceils. in contrast, intrathecai administration of morphine has a disfacilitating effect on the on-ceils, presumably by removing excitatory influences originating in the spinal cord. Supported by PHS grants DA01949 and DA05603
Poster 54 BROWN Th-Fri ACC
Hall
Abs No
BIM OF INVESTIGATION : The interpeduncular nucleus (IPN)--a little midbrain area with cholinergic input--may affect pain. IPN lesions learning of avoidance behaviour, and during anaesthesia the IPN is metabolically active. An IPN influence on the nucleus raphe magnus predicted.
E
858
studied impede unusually is
METHODS: Rats (300g) were anaesthetised with pentobarbital, placed in a stereotaxic head holder. A metal recording microelectrode was put in the NRM, and an electrically insulated 27g needle put in the IPN--for both drug delivery and electrical stimulation. Postmortem histology confirmed electrode positions. Drugs used were acetylcholine (ACh), glutamate (Glu), and g-aminobutyric acid (GABA), each 50 mM in 0.5-1~1 injected for 30s. NRM cells were classified as on-, off-, and neutral, as per their RESULTS response to noxious electrical or mechanical stimulation of the hindpaw skin. ACR, Glu, and electrical stimulation in the IPN mainly inhibited (never excited) off-cells and mainly excited (never inhibited) on-cells. Neutral cells were not studied. If, as previous work suggests, on-cell activity causes wperalgesia and off-cell activity analgesia, then IPN output to the NRM should be hyperalgetic, probably via a synapse in the dorsal raphe.
CIRCUITRY UNKING OPlATE-SENStTlVE NOCICEPTIVE MODULATORY SYSTEMS IN ROSTRAL WNTROMEDtAL MEDULlA , FERWUEDUCTAL GRAY AND SPtNAL CORD. j&M, / . . Helnncher. M.M.Morgan and H.L. Fields. Dept. Neurology, ,Unlversity of California, San Francisco, CA 94143
ACC Hall Abs No
859
E
1
J AIM OF INVESTIGATION: On-cells are a class of putative noclceptive modulating neurons identified in the rostra1 ventromedial medulla (RVM) of the barbiturate-anesthetized rat that are thought to exert a permissive, or even facttitatory, role in descending modulation of nocicepttve transmission. Morphine, when given in doses sufficient to inhibit nocifenslve reffexes, reliably suppresses the spontaneous and nocifensor-reflex related firing of RVM on-cells. Suppression of on-cell activity is observed whether morphine is given systemically, into the intrathecal space, or microinjected into the midbrain pertaqueductal gray (PAG). The present experiments used direct activation of on-cells with iontophoretically-apptted iglutamate as an indication of whether morphine-induced suppression of on-cell firing reflected a postsynaptic inhibition, or a dlsfacititatlon resulting from blockade of an excitatory element among the afferents to the on-cell. METHODS: Rats were maintained in a lightly-anesthetized state by a continuous infusion of methohexitai. Physiologically characterized on-ceils were excited by iontophoreticalty-apptiid pulses of i-glutamate (ZO90 nA, 10 s pulse every 20 s). The tail-flick (TF) response to noxious heat was evoked at 5 min intervals in order to verify the antinociceptive effect of morphine given systemically (1.255 mg/kg), intrathecally (lo-15 ug), or by microinjection in the PAG (7.515 ug). RESULTS: Following either systemic or PAG administration of morphine, glutamate-evoked firing of onceils was suppressed along with spontaneous activity and the TF response. Intrathecally-administered morphine sufficient to block the TF did not depress glutamate-evoked firing, even though spontaneous and TFrelated activity were completely suppressed. CONCLUSIONS: These obsenratlons provide positive evidence that administration of morphine either systemically or by microinjection in the PAG causes an inhibition of on-ceils. in contrast, intrathecai administration of morphine has a disfacilitating effect on the on-ceils, presumably by removing excitatory influences originating in the spinal cord. Supported by PHS grants DA01949 and DA05603