Enhanced analgesic cholinergic tone after neuropathy

Abstract

18At the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory 19 processing. Increasing the level of spinal ACh induces analgesia in naïve animals or in situation of 20 acute pain in the clinics, but whether this is still the case in situations or models of chronic pain is 21 controversial. Here, we demonstrate the persistence, and even increased impact of the analgesic 22 cholinergic tone acting through nicotinic receptors in neuropathic mice. The neuropathy does not 23 affect the number and properties of dorsal horn cholinergic neurons, proposed to be the source of 24 spinal ACh. Subthreshold doses of acetylcholinesterase (AChE) inhibitors in sham animals become 25 anti-allodynic in cuff mice suggesting that the alterations occur in the cholino-receptive neurons. Thus 26 endogenous cholinergic signaling can be manipulated with low doses of drugs to relieve mechanical 27 allodynia in animal neuropathy models. This opens new avenues with potentially fewer side effects for 28 neuropathic pain treatment. 29 540 PKCgamma interneurons within the medullary dorsal horn revealed by electrophysiologic 541 and morphologic approach. Pain, 156(9),