Abstract
Although considerable evidence exists that spinal neurokinin1 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, neurokinin3 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]-MePhe7-NKB, a selective ligand for neurokinin3 receptors, in the superficial dorsal horn of the spinal cord. Specific binding of [125I]-MePhe7-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. Neurokinin3 receptor messenger RNA levels doubled in the dorsal spinal cord at 12h and remained elevated for at least four days. The change in neurokinin3 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 neurokinin3 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 neurokinin3 receptors may play a role in spinal neurotransmission of injured rats and require consideration of other tachykinins as physiologically relevant ligands to spinal neurokinin3 receptors. Copyright (C) 2000 IBRO.
Original language | English (US) |
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Pages (from-to) | 801-811 |
Number of pages | 11 |
Journal | Neuroscience |
Volume | 98 |
Issue number | 4 |
DOIs | |
State | Published - Jul 2000 |
Bibliographical note
Funding Information:The authors wish to thank Michelle Winter and Lia Abrahams for advice and technical assistance during the course of these studies. This work was supported by funds from the National Institutes of Health (NS17702, V.S.S.), and a bridging grant from KUMC Research Inc. (K.E.M.). D.R.L. and M.A.R. were supported by a training grant funded by NIDA (DA07234).
Keywords
- Hyperalgesia
- Inflammation
- Nociception
- Rat
- Spinal cord
- Substance P