Choline, an alpha7 nicotinic acetylcholine receptor agonist, alleviates hyperalgesia in a rat osteoarthritis model

It has been suggested that activation of alpha7 nicotinic acetylcholine receptors (α7nAChR) could alleviate acute and chronic pain in various abnormal pain models. However, it is unclear whether the stimulation of α7nAChRs has anti-hyperalgesic effects on osteoarthritis. Therefore, we tested whether choline, an α7nAChR agonist, could alleviate chronic inflammatory pain in an osteoarthritis model. Osteoarthritis was induced by injection of monoiodoacetic acid (MIA) into the synovial cavity of the knee joints in rats. Pain was assessed by responses to stimuli on the plantar surface: paw withdrawal threshold (PWT) by up-down methods using a series of von Frey filaments, and paw withdrawal latency (PWL) using radiation heat. Both PWT and PWL decreased after MIA injection, indicating development of mechanical and thermal hyperalgesia. Subsequent intraperitoneal choline injection increased both PWT and PWL. PWT increased in response to choline injections (5-50 mg/Kg) in a dose dependent manner. PWL increased significantly in a similar fashion in response to choline (20 and 50 mg/Kg). However, intraarticular injection of choline did not result in any change in PWT or PWL. Intrathecal choline increased PWT and PWL. The anti-hyperalgesic effect of intraperitoneal choline was completely blocked by methyllycaconitine when it was injected intrathecally 10 min before the choline treatment. These results show that choline could alleviate mechanical and heat hyperalgesia via spinal α7nAChR in the MIA-induced inflammation pain model.