Time-dependent changes in neurokinin(3) receptors and tachykinins during adjuvant-induced peripheral inflammation in...

Although considerable evidence exists that spinal neurokinin(1) receptors are involved in central sensitization of nociception, recent evidence from knockout studies indicates that other neurokinin receptors in the spinal cord may mediate a portion of the hyperalgesia caused by substance P and neurokinin A. The present study determined whether the second most abundant class of neurokinin receptors, neurokinin(3) receptors, are regulated during persistent peripheral inflammation. Inflammation in the hind paw of the rat was induced by intraplantar injection of complete Freund's adjuvant. Receptor autoradiography revealed specific binding of [125I]-MePhe(7)-NKB, a selective ligand for neurokinin(3) receptors, in the superficial dorsal horn of the spinal cord. Specific binding of [125I]-MePhe(7)-NKB in the medial dorsal horn was reduced bilaterally two days after unilateral injection of complete Freund's adjuvant. Binding returned to basal levels four days after injection of complete Freund's adjuvant. Neurokinin(3) receptor messenger RNA levels doubled in the dorsal spinal cord at 12h and remained elevated for at least four days. The change in neurokinin(3) receptor binding and messenger RNA during adjuvant-induced inflammation may be a consequence of activation 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 neurokinin B, was reduced bilaterally during adjuvant-induced inflammation.Collectively, these data indicate that spinal neurokinin(3) receptors may play a role in spinal neurotransmission of injured rats and require consideration of other tachykinins as physiologically relevant ligands to spinal neurokinin(3) receptors.