Plasticity in action of intrathecal clonidine to mechanical but not thermal nociception after peripheral nerve injury.
BACKGROUND
Intrathecal clonidine reduces tactile allodynia in animal models of neuropathic pain, and this effect is blocked by atropine. However, the role of tonic spinal cholinergic activity and its interaction with alpha2-adrenergic systems in normal and neuropathic conditions and to different sensory methods has not been systematically examined. The authors examined cholinergic receptor involvement in thermal and mechanical sensitivity in normal and neuropathic animals and its interaction with intrathecal clonidine.


METHODS
Normal rats and rats that received L5/L6 spinal nerve ligation were tested with acute radiant heat, paw pressure, and punctate mechanical stimulation before and after the intrathecal administration of saline, the muscarinic receptor antagonist, atropine, or a toxin to destroy cholinergic neurons, and then after intrathecal clonidine.


RESULTS
Atropine, the cholinergic neuronal toxin, and saline did not alter baseline withdrawal thresholds. In nerve-injured rats, neither saline nor atropine altered antinociception from clonidine to a thermal stimulus, but atropine reduced the effect of clonidine to von Frey filament withdrawal threshold (34 +/- 5.6 vs. 14 +/- 5.8 g [mean +/- SEM], saline vs. atropine; P < 0.05) and to withdrawal threshold to paw pressure after clonidine (174 +/- 18 g vs. 137 +/- 16 g, saline vs. atropine; P < 0.05).


CONCLUSIONS
These data suggest that after nerve injury, mechanical but not thermal antinociception from intrathecal clonidine relies on a muscarinic interaction, because only mechanical antinociception was antagonized by atropine. These results do not favor a regulation of nociceptive transmission by a tonic release of acetylcholine in nerve-injured rats.
Paqueron
Xavier
X
Department of Anesthesiology, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
Conklin
Dawn
D
Eisenach
James C
JC
D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001388:Aziridines / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006358:Hot Temperature / Q000009:adverse effects*; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D059348:Peripheral Nerve Injuries; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000473:pathology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D001388:Aziridines; D018727:Muscarinic Antagonists; D009466:Neuromuscular Blocking Agents; D009498:Neurotoxins; D001285:Atropine; C044894:ethylcholine aziridinium; D003000:Clonidine; D002794:Choline; D000109:Acetylcholine