Nerve growth factor induces P2X(3) expression in sensory neurons

Glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) are neuroprotective for subpopulations of sensory neurons and thus ar e candidates for pain treatment. However, delivering these factors to damag ed neurons will invariably result in undamaged systems also being treated, with possible consequences for sensory processing. In sensory neurons the p urinergic receptor P2X(3) is found predominantly in GDNF-sensitive nocicept ors. ATP signalling via the P2X(3) receptor may contribute to pathological pain, suggesting an important role for this receptor in regulating nocicept ive function. We therefore investigated the effects of intrathecal GDNF or NGF on P2X(3) expression in adult rat spinal cord and dorsal root ganglia ( DRG). In control spinal cords, P2X(3) expression was restricted to a narrow band of primary afferent terminals within inner lamina II (IIi). Glial cel l line-derived neurotrophic factor treatment increased P2X(3) immunoreactiv ity within lamina IIi but not elsewhere in the cord. Nerve growth factor tr eatment, however, induced novel P2X(3) expression, with intense immunoreact ivity in axons projecting to lamina I and outer lamina II and to the ventro medial afferent bundle beneath the central canal. In the normal DRG, we fou nd a greater proportion of P2X(3)-positive neurons at cervical levels, many of which were large-diameter and calcitonin gene-related peptide-positive. In both cervical and lumbar DRG, the number of P2X(3)-positive cells incre ased following GDNF or NGF treatment. De novo expression of P2X(3) in NGF-s ensitive nociceptors may contribute to chronic inflammatory pain.