Extraterritorial neuropathic pain correlates with multisegmental elevationof spinal dynorphin in nerve-injured rats

Neuropathic pain is often associated with the appearance of pain in regions not related to the injured nerve. One mechanism that may underlie neuropat hic pain is abnormal, spontaneous afferent drive which may contribute to NM DA-mediated central sensitization by the actions of glutamate and by the no n-opioid actions of spinal dynorphin. In the present study, injuries to lum bar or sacral spinal nerves elicited elevation in spinal dynorphin content which correlated temporally and spatially with signs of neuropathic pain. T he increase in spinal dynorphin content was coincident with the onset of ta ctile allodynia and thermal hyperalgesia. Injury to the lumbar (L-5/L-6) sp inal nerves produced elevated spinal dynorphin content in the jpsilateral d orsal spinal quadrant at the L-5 and L-6 spinal segments and in the segment s immediately adjacent. Lumbar nerve injury elicited ipsilateral tactile al lodynia and thermal hyperalgesia of the hindpaw. In contrast, S-2 spinal ne rve Ligation elicited elevated dynorphin content in sacral spinal segments and bilaterally in the caudal lumbar spinal cord. The behavioral consequenc es of S-2 spinal nerve ligation were also bilateral, with tactile allodynia and thermal hyperalgesia seen in both hindpaws. Application of lidocaine t o the site of S-2 ligation blocked thermal hyperalgesia and tactile allodyn ia of the hindpaws suggesting that afferent drive was critical to maintenan ce of the pain state. Spinal injection of antiserum to dynorphin A((1-17)) and of MK-801 both blocked thermal hyperalgesia, but not tactile allodynia, of the hindpaw after S-2 ligation. These data suggest that the elevated sp inal dynorphin content consequent to peripheral nerve injury may drive sens itization of the spinal cord, in part through dynorphin acting directly or indirectly on the NMDA receptor complex. Furthermore, extrasegmental increa ses in spinal dynorphin content may partly underlie the development of extr aterritorial neuropathic pain. (C) 2000 International Association for the S tudy of Pain. Published by Elsevier Science B.V. All rights reserved.