Nitric oxide and nitric oxide synthases are key players in synaptic plasticity events in the spinal cord, which underly the development of chronic pain states. To date, little is known about the molecular mechanisms regulating the activity of nitric oxide synthases in nociceptive systems. The present study was aimed at the immunohistochemical determination of the expression of a nitric oxide synthase-interacting protein (NOSIP) in the rat spinal cord and dorsal root ganglia and studying its regulation in states of nociceptive hypersensitivity in a rat model of post-inflammatory pain. NOSIP is predominantly expressed in nociceptive primary neurons and in neurons of the spinal dorsal horn and the number of NOSIP-positive spinal neurons increases significantly following induction of unilateral intraplantar injection of complete Freund's adjuvant. Thus, NOSIP may modulate nitric oxide homeostasis in physiological and pathological pain conditions. (C) 2003 Elsevier Ireland Ltd. All rights reserved.