Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

Misaki Matsumoto, Weijiao Xie, Makoto Inoue, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

Abstract

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-, Aδ- and Aβ-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. Conclusion: 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.

Original languageEnglish (US)
Article number41
JournalMolecular Pain
Volume3
DOIs
StatePublished - Dec 19 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Fingerprint

Dive into the research topics of 'Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents'. Together they form a unique fingerprint.

Cite this