Donepezil reverses intermittent stress-induced generalized chronic pain syndrome in mice

Abstract

Numbers of words in the Discussion 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. JPET #222414