Spinal antinociception mediated by a cocaine-sensitive dopaminergic supraspinal mechanism.
The role of dopaminergic descending supraspinal processes in mediating the antinociceptive action of cocaine was studied in the rat using a combination of extracellular neuronal recording and behavioral techniques. Neurons in the superficial laminae (I-II) of the spinal dorsal horn with receptive fields on the tail were recorded in anesthetized rats using insulated metal microelectrodes. Stimulation of the receptive field with either high intensity transcutaneous electrical pulses or with an infrared CO2 laser beam produced a biphasic increase in dorsal horn unit discharge. Conduction velocity estimates indicated that the early discharge corresponded to activity in A delta whereas the late response corresponded to activity in C afferent fibers. Cumulative doses of cocaine (0.1-3.1 mg/kg i.v.) inhibited the late response to either electrical or laser stimulation in a dose-related manner. The early response to laser, but not electrical, stimulation was also suppressed by cocaine. Neurons in the spinal dorsal horn with receptive fields on the ipsilateral hindpaw were activated by natural noxious (pinch) or innocuous (tap) somatic stimulation. Cocaine selectively suppressed nociceptively evoked dorsal horn unit discharge. This antinociceptive effect was dose-related (0.3-3.1 mg/kg, i.v.) and antagonized by eticlopride (0.05-0.1 mg/kg, i.v.), a selective D2 dopamine receptor blocker. The same doses of cocaine failed to inhibit the responses of dorsal horn neurons to low threshold innocuous stimulation. Complete thoracic spinal cord transection eliminated the antinociceptive effect of cocaine on dorsal horn neurons and also eliminated the cocaine-induced attenuation of the tail-flick reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurology Service (127), Veterans Affairs Medical Center, Ann Arbor, MI 48105.
J A
JA
Kiritsy-Roy
B C
BC
Shyu
P J
PJ
Danneman
T J
TJ
Morrow
C
C
Belczynski
K L
KL
Casey
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D007259:Infrared Rays; D007834:Lasers; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D010775:Photic Stimulation; D051381:Rats; D011930:Reaction Time; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
D003042:Cocaine; D004298:Dopamine