The cytokine TNFα increases the proportion of DRG neurones expressing the TRPV1 receptor via the TNFR1 receptor and ERK activation

TNF alpha is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. The pronociceptive action of TNF alpha may be mediated at least in part by activation of the TRPV1 receptor which transduces heat stimuli in primary nociceptive afferents and mediates thermal hyperalgesia. In the present study, we investigated in cultured dorsal root ganglion (DRG) neurones, the somata of primary afferent fibres, whether TNF alpha increases TP-PV1 receptor expression. We found that long-term exposure of DRG neurones of both rat and mouse to TNF alpha significantly increased the proportion of DRG neurones expressing TRPV1 receptor-like immunoreactivity. This TNF alpha effect was abolished in mice DRG neurones when DRG cultures were obtained from tnfr1/2(-/-) and tnfr1/2(-/-), but not from tnfr1/2(-/-) mice. Furthermore, we found that activation of ERK but not of p38 kinase or cyclooxygenases is critically involved in the TNF alpha-induced increase of TRPVI receptor expression. (c) 2007 Elsevier Inc. All rights reserved.