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

Abstract

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.