Founder of Health Rising and Phoenix Rising
Something completely new: Donezipil is a centrally acting reversible acetylcholinesterase inhibitor. This is an laboratory animal study so it's quite preliminary but the drug did completely remove allodynia and increased pain sensitivity...
J Pharmacol Exp Ther. 2015 Mar 24. pii: jpet.114.222414. [Epub ahead of print] Donepezil reverses intermittent stress-induced generalized chronic pain syndrome in mice. Mukae T1, Uchida H1, Ueda H2.
Treatment for fibromyalgia is an unmet medical need. To develop novel therapies for the treatment of fibromyalgia, we explored pain therapeutic actions of existing pharmaceuticals, which inhibit the somatic symptoms frequently observed in fibromyalgia patients. The present study first examined the therapeutic actions of pilocarpine, which inhibits dry-eye and dry-mouth symptoms, using an experimental fibromyalgia-like chronic pain model produced by intermittent cold stress (ICS) in mice. A single intraperitoneal (i.p.) and intracerebroventricular (i.c.v.), but not intrathecal, pilocarpine administration attenuated ICS-induced thermal hyperalgesia and mechanical allodynia, and this action was abolished by muscarinic antagonist pirenzepine (i.c.v.). Treatment with 1-10 μg/kg donepezil (i.p.), which can easily penetrate into the brain, also showed similar therapeutic effects. Importantly, we found that both of pilocarpine and donepezil produced anti-hyperalgesic effects via supraspinal action.
Furthermore, repeated donepezil treatments completely cured the ICS-induced hyperalgesia and allodynia even after the cessation of drug treatments. Acute and chronic treatments of these cholinomimetics had no effects on the nociceptive threshold in control animals. In contrast, the lack of morphine (i.c.v.) analgesia initially observed in the ICS model remained in ICS model mice treated with long-term donepezil.
Collectively, these findings suggest that stimulation of the muscarinic cholinergic system effectively inhibits some mechanisms underlying chronic pain in the ICS model, but not the lack of descending pain inhibitory mechanisms, which is driven by central morphine.