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The Journal of Neuroscience, July 1, 1999, 19(13):5482-5492

Chronic Pain is Associated with Increased TrkA Immunoreactivity in Spinoreticular Neurons

Sophie Pezet¹, Brigitte Onténiente¹, Gaël Grannec¹, and Bernard Calvino^{1, 2}

¹ Institut National de la Santé et de la Recherche Médicale U421, Institut Mondor de Médecine Moléculaire, Faculté de Médecine, F-94010 Créteil Cedex, France, and ² Faculté des Sciences, Université de Paris XII, F-94010 Créteil Cedex, France

Repetitive noxious stimulation leads to permanent adaptive changes of central pathways involved in the genesis and integration of nociception. Several classes of neurotrophic factors that affect brain plasticity are also involved in the regulation of sensory functions in adulthood. To investigate a putative role of nerve growth factor (NGF) in central plasticity linked to chronic pain, modifications in immunoreactivity (IR) for the high-affinity NGF receptor, TrkA, were studied at spinal levels in a rat model of inflammatory chronic pain, adjuvant-induced arthritis (AIA). We report a specific increase in the number of TrkA-IR profiles in laminae V-VI at lumbar levels L3 and L4 in arthritic rats. Tract tracing using FluoroGold injections in the ventrobasal complex of the thalamus and in the brainstem showed that these increased TrkA-IR profiles are spinoreticular neurons. Dual labeling with calcitonin gene-related peptide or substance P showed that TrkA-IR neurons were mainly located in projection fields of small- to medium-sized primary afferent fibers, which convey nociceptive inputs. These results suggest that TrkA-containing neurons of the spinal dorsal horn participate in the first central relay of transmission of nociceptive information to supraspinal centers. Enhanced numbers of TrkA-IR neurons during AIA strongly support the hypothesis of a participation of NGF in adaptive mechanisms of central nociceptive pathways observed in chronic pain states.

Key words: nerve growth factor; NGF; TrkA; adjuvant-induced arthritis; substance P; CGRP; spinal cord; rat

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19135482-11$05.00/0

This article has been cited by other articles:

				L. Bueno, J. Fioramonti, and R. Garcia-Villar Pathobiology of Visceral Pain: Molecular Mechanisms and Therapeutic Implications: III. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G670 - G676. [Abstract] [Full Text] [PDF]

				The Neuroscientist comments: NGF and central pain mechanisms Neuroscientist, February 1, 2000; 6(1): 1 - 1. [PDF]

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