Antagonist of nicotinic acetylcholine receptors (nAChR) enhances formalin-induced nociception in rats: tonic role of nAChRs in the control of pain following injury

Following tissue injury, spinal neurons increase in spontaneous activity and in responsiveness to peripheral stimulation. These changes in spinal neurons may underlie abnormal pain behavior. Nicotinic acetylcholine receptor (nAChR) agonists are analgesic when evaluated in animal models of pain, but it is not known if the nAChRs differentially modulate acute and tonic pain. To test this, mecamylamine, a non-subtype selective nAChR antagonist, was systemically injected into rats prior or after hind paw injection of formalin. Formalin injection results in biphasic pain-related behaviors, characterized by a first phase (i.e. acute pain) immediately following formalin injection, then by a second phase (i.e. tonic pain) 15-60 min after formalin injection. Either pre- or post-formalin treatment with mecamylamine decreased phase 1 behaviors and significantly increased phase 3 pain behaviors in a dose-dependent manner. These results suggest that nAChRs may exert opposing effects on acute versus tonic pain and, as such, may have implications for the potential development of nAChR ligands for the treatment of pain. (C) 2001 Elsevier Science B.V. All rights reserved.