Supraspinal and systemic administration of the nicotinic-cholinergic agonist (+/-)-epibatidine has inhibitory effects on C-fiber reflexes in the rat.
This study assessed the effects of the nicotinic agonist (+/-)-epibatidine (EPIB) on the C-fiber flexor reflex in the anesthetized rat. Electrical stimulation of the hindpaw produces a long latency (> 150 ms) C-fiber mediated electromyographic (EMG) burst in hindlimb flexor muscles. EPIB (0.01, 0.03 micromol/kg, i.p.) significantly reduced (p < 0.05) C-fiber -related EMG activity by 46 and 64%, respectively. This effect was similar to that produced by the opioid morphine (21.0 micromol/kg, i.p.) and the NMDA receptor antagonist MK-801 (3.0 micromol/kg, i.p.). Nicotinic receptor blockade with the antagonists mecamylamine (5.0 micromol/kg, i.p.) and chlorisondamine (23.0 nmol/rat, intracerebroventricular) attenuated the effects of systemic EPIB on the C-fiber reflex. EPIB injection (0.04 nmol/rat) into the nucleus raphe magnus significantly decreased C-fiber EMG activity by 67%, suggesting a supraspinal site of action. In contrast, EPIB (0.6 nmol/rat) administered into the lumbar spinal cord significantly increased the C-fiber reflex by 117%. In summary, systemic and supraspinal EPIB exerted an inhibitory effect on central pain transmitting pathways, while a stimulatory effect is elicited in the spinal cord. The inhibitory effects are consistent with the reported analgesic properties of EPIB. The excitatory effect may be related to the reported algogenic responses when EPIB is administered intrathecally.
Radek
Richard J
RJ
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. rich.j.radek@abbott.com
Curzon
Peter
P
Decker
Michael W
MW
D000704:Analysis of Variance; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002714:Chlorisondamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007269:Injections, Intra-Arterial / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D009020:Morphine / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009294:Narcotics / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000528:radiation effects; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000528:radiation effects; D012018:Reflex / Q000187:drug effects* / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D016291:Dizocilpine Maleate; D009020:Morphine; D002714:Chlorisondamine; C082748:epibatidine