Enhanced analgesic cholinergic tone after neuropathy

Abstract

At the spinal cord level, a tone of endogenous acetylcholine (ACh) modulates nociceptive sensory processing. Increasing the level of spinal ACh induces analgesia in naive animals or in situation of acute pain in the clinics, but whether this is still the case in situations or models of chronic pain is controversial. Here, we demonstrate the persistence, and even increased impact of the analgesic cholinergic tone acting through nicotinic receptors in neuropathic mice. The neuropathy does not affect the number and properties of dorsal horn cholinergic neurons, proposed to be the source of spinal ACh. Subthreshold doses of acetylcholinesterase (AChE) inhibitors in sham animals become anti-allodynic in cuff mice suggesting that the alterations occur in the cholino-receptive neurons. Thus endogenous cholinergic signaling can be manipulated with low doses of drugs to relieve mechanical allodynia in animal neuropathy models. This opens new avenues with potentially fewer side effects for neuropathic pain treatment.