Loss of muscarinic M4 receptors in spinal cord of arthritic rats: implications for a role of M4 receptors in pain response

Abstract Changes in the levels of muscarinic M 4 receptors in spinal cord of acute and chronic arthritic rats (animal models of pain) were studied by receptor autoradiography using muscarinic M 4 receptor subtype selective ligand. Arthritis was induced in female Lewis rats by single intradermal injection of heat-killed Mycobacterium butyricum and sacrificed 12 days (acute group) and 30 days (chronic and control groups) after induction of arthritis. Our results demonstrate significant reduction in the level of M 4 receptors in the spinal cord (Rexed laminae I–X) of acute and chronic arthritic rats compared to controls. These findings suggest that the muscarinic M 4 receptor subtype may be involved in cholinergic mechanisms of analgesia.