Differential regulation of NGF receptors in primary sensory neurons by adjuvant-induced arthritis in the rat

In the adult brain, neurotrophins play a key role in adaptive processes lin ked to increased neuronal activity. A growing body of evidence suggests tha t chronic pain results from long-term plasticity of central pathways involv ed in nociception. We have investigated the involvement of nerve growth fac tor (NGF) in adaptive responses of primary sensory neurons during the cours e of a long-lasting inflammatory pain model. The amount and distribution of the NGF receptors p75(NTR) and TrkA were measured in the dorsal horn and d orsal root ganglia (DRG) of animals subjected to Freund's adjuvant-induced arthritis (AIA). We observed an increased immunoreactivity of both receptor s in the central terminals of primary sensory neurons in the arthritic stat e. The increases were seen in the same population of afferent terminals in deep dorsal horn laminae. These changes paralleled the variations of clinic al and behavioral parameters that characterize the course of the disease. T hey occurred in NGF-sensitive, but not GDNF-sensitive, nerve terminals. How ever, p75(NTR) and TrkA protein levels in the DRG (in the cell body of thes e neurons) showed different response patterns. An immediate rise of p75(NTR ) was Seen in parallel with the initial inflammation that developed after a dministration of Freund's adjuvant in hindpaws. In contrast, increases of t he mature (gp140(trk)) form of TrkA occurred later and seemed to be linked to the development of the long-lasting inflammatory response. The changes i n receptor expression were observed exclusively at lumbar levels, L3-L5, so matotopically appropriate for the inflammation. Together, these results imp licate NGF in long-term mechanisms accompanying chronic inflammatory pain, via the up-regulation of its high affinity receptor, and offer additional e vidence for differential processes underlying short- versus long-lasting in flammatory pain. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.