Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents.
BACKGROUND
We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized.


RESULTS
Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I-III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, Adelta- and Abeta-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests.


CONCLUSIONS
These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition.
Matsumoto
Misaki
M
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. dm05052b@stcc.nagasaki-u.ac.jp
Xie
Weijiao
W
Inoue
Makoto
M
Ueda
Hiroshi
H
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D009433:Neural Inhibition; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009538:Nicotine / Q000008:administration & dosage*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D013116:Spinal Cord / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D016376:Oligonucleotides, Antisense; D009538:Nicotine; D002795:Choline O-Acetyltransferase