Time-dependent changes in neurokinin3 receptors and tachykinins during adjuvant-induced peripheral inflammation ln the rat

Although considerable evidence exists that spinal neurokinin(1) receptors a re involved in central sensitization of nociception, recent evidence from k nockout studies indicates that other neurokinin receptors in the spinal cor d may mediate a portion of the hyperalgesia caused by substance P and neuro kinin A. The present study determined whether the second most abundant clas s of neurokinin receptors, neurokinin(3) receptors, are regulated during pe rsistent peripheral inflammation. Inflammation in the hind paw of the rat w as induced by intraplantar injection of complete Freund's adjuvant. Recepto r autoradiography revealed specific binding of [I-125]-MePhe(7)-NKB, a sele ctive ligand for neurokinin(3) receptors, in the superficial dorsal horn of the spinal cord. Specific binding of [I-125]-MePhe(7)-NKB in the medial do rsal horn was reduced bilaterally two days after unilateral injection of co mplete Freund's adjuvant. Binding returned to basal levels four days after injection of complete Freund's adjuvant. Neurokinin(3) receptor messenger R NA levels doubled in the dorsal spinal cord at 12 h and remained elevated f or at least four days. The change in neurokinin(3) receptor binding and mes senger RNA during adjuvant-induced inflammation may be a consequence of act ivation of the receptor. Spinal levels of potential endogenous ligands for spinal neurokinin(3) receptors were measured by radioimmunohistochemistry. Immunoreactive substance P but not neurokinin B peptide 2, a marker for neu rokinin B, was reduced bilaterally during adjuvant-induced inflammation. Collectively, these data indicate that spinal neurokinin(3) receptors may p lay a role in spinal neurotransmission of injured rats and require consider ation of other tachykinins as physiologically relevant ligands to spinal ne urokinin3 receptors. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.