The Open Pain Journal

2009, 2 : 41-52
Published online 2009 July 23. DOI: 10.2174/1876386300902010041
Publisher ID: TOPAINJ-2-41

RESEARCH ARTICLE
 Role of NGF in Neuronal Plasticity in the Lateral Reticular Nucleus in Chronic Inflammatory Pain

Sophie Pezeta, * , Marchandb , Karine Thibaulta , Celine Dauvergnec,d , Grisb , Georges M. Smithe , Stephen B. McMahonb and Bernard Calvino
a Laboratoire de Neurobiologie, UMR CNRS 7637, Ecole Supérieure de Physique et de Chimie Industrielles, 10, rue Vauquelin 75005 Paris, France
b Neurorestoration Group, The Wolfson Centre for Age-Related Diseases, King’s College London, Guy’s Campus, London SE1 1UL, UK
c Laboratoire de Physiologie de la Manducation, UFR Odontologie, Université Paris VII Denis Diderot, 4 Place Jussieu, Bât A, 2 Étage 75252 Paris Cedex 05, France
d CRicm UMRS 975 INSERM, UMR 7225 CNRS, UPMC ; «Equipe Douleurs», Faculté de Médecine Pitié-Salpêtriére, 91 Bd de l’Hôpital, 75013 Paris, France
e Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, USA

* Address correspondence to this author at the UMR CNRS 7637, EcoleSupérieure de Physique et de Chimie Industrielles, 10 rue Vauquelin, 75005 Paris, France; Tel: (33) 1 40 79 51 83; Fax: (33) 1 40 79 47 57; E-mail: sophie.pezet@espci.fr

ABSTRACT

In pathological states, repetitive inputs from the ascending pathways involved in the genesis and integration of nociception, leads to molecular, anatomical and electrophysiological adaptive changes of these pathways, contributing to the development of pain chronicity. In the past, neurotrophic factors have been implicated in neuronal plasticity in adult central nervous system. We have previously described plastic changes associated with the up-regulation of NGF’s high affinity receptor, TrkA, in the spinoreticular pathway in a chronic inflammatory pain model of arthritis induced by complete Freund’s adjuvant. The present study investigated the role of central NGF in the maintenance of inflammatory pain. Analysis of TrkA and NGF expression revealed that they are expressed in the medial thalamus and several reticular nuclei of the brain stem such as the lateral reticular nucleus (LRt) and not in pathways classically described to be involved in the sensory-discriminative aspect of pain such as the lateral thalamus. In addition NGF was over-expressed in the LRt, lateral thalamus and cortex of polyarthritic rats. Using micro-injection of an adenoviral vector synthesizing NGF (or green fluorescent protein) in the LRt of normal animals, we showed that increased NGF levels in the LRt leads to the development of mechanical hypersensitivity and increased nocifensive behavior following an inflammatory stimulus. These results suggest that, NGF acts centrally as a possible molecular inducer of synaptic plasticity in the LRt in conditions of chronic inflammatory pain.