부산대학교 도서관

Purpose: Tumor necrosis factor-[alpha] (TNF-[alpha]) is a pro-inflammatory cytokine and involves in a variety of pain conditions. Some findings suggest that TNF-[alpha] may act directly on primary afferent neurons to induce acute pain hypersensitivity through non-transcriptional regulation. This study investigated whether TNF-[alpha] had an effect on functional activity of P2X3 receptors in primary sensory neurons. Herein, we report that a brief (5 min) application of TNF-[alpha] rapidly enhanced the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Methods: Electrophysiological recordings were carried out on rat DRG neurons, and nociceptive behavior was quantified in rats. Results: A brief (5 min) exposure of TNF-[alpha] rapidly increased P2X3 receptor-mediated and [alpha],[beta]-methylene-ATP ([alpha],[beta]-meATP)-evoked inward currents in a dose-dependent manner. The potentiation of P2X3 receptor-mediated ATP currents by TNF-[alpha] was voltage-independent. TNF-[alpha] shifted the concentration-response curve for [alpha],[beta]-meATP upwards, with an increase of 31.57 [+ or -] 6.81% in the maximal current response to [alpha],[beta]-meATP This acute potentiation of ATP currents by TNF-[alpha] was blocked by p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by non-selective cyclooxygenase inhibitor indomethacin, suggesting involvement of p38 MAPK, but not cyclooxygenase. Moreover, intraplantar injection of TNF-[alpha] and [alpha],[beta]-meATP produced a synergistic effect on mechanical allodynia in rats. TNF-[alpha]-induced mechanical allodynia was also alleviated after local P2X3 receptors were blocked. Conclusion: These results suggested that TNF-[alpha] rapidly sensitized P2X3 receptors in primary sensory neurons via a p38 MAPK dependent pathway, which revealed a novel peripheral mechanism underlying acute mechanical hypersensitivity by peripheral administration of TNF-[alpha]. Keywords: electrophysiology, dorsal root ganglion neuron, nociceptive response, P2X3 receptor, tumor necrosis factor-[alpha]
Introduction During tissue damages and inflammation, a variety of mediators are released and contribute to peripheral sensitization by regulating activity of ion channels that mediate the transduction of pain signaling. [...]