Although microglial P2X4 receptors (P2X4R) activation is directly associated with the pathogenesis of neuropathic pain, in dorsal root ganglia (DRG) their role on development of distinct pain states has been scarcely studied. This research investigates P2X4R signaling in DRG during both acute and chronic hyperalgesia induced either by neuropathic (paclitaxel) or pro-inflammatory mediator (Prostaglandin E2 - PGE2). Inflammatory hyperalgesia was induced in male Wistar rats (6-8 weeks-old) after 1 (acute) or 14 (chronic) intraplantar injections of PGE2 (100 ng/50 μL/paw).  Neuropathic hyperalgesia was induced with 1 (acute) or 4 (chronic) intraperitoneal injections of paclitaxel (1 mg/kg). Rats were treated with either ODN antisense (30 μg/10 μL - intrathecal) or selective P2X4R antagonist, PSB 12062 (1 mmol/5 μL - ganglionic) and mechanical hyperalgesia was measured with electronic von Frey. DRG were harvested to immunohistochemistry, immunogold and western blot. P2X4R expression was upregulated in paclitaxel- treated rats and the knockdown, as well as the antagonist treatment, reverted paclitaxel-induced neuropathic hyperalgesia but not PGE2-induced inflammatory one. A-fibers are the main responsible for paclitaxel-induced pain once that, after desensitization of the C-fibers, neuropathic but not inflammatory pain was sustained. P2X4R were in neurons of both C- and A-fibers and in satellite cells; positive gold labeling was also detected in cytoplasm and plasma membrane of both neuron and satellite cells. These data suggest that prior P2X4R pathway activation in DRG contributes to the development and maintenance of neuropathic pain but might not be essential to inflammatory pain.

P2X4 RECEPTOR IN DORSAL ROOT GANGLIA IS INVOLVED IN NEUROPATHIC BUT NOT IN INFLAMMATORY HYPERALGESIA