Brain research bulletin
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Brain research bulletin · Nov 2008
Extracellular signal-regulated kinases mediate melittin-induced hypersensitivity of spinal neurons to chemical and thermal but not mechanical stimuli.
Subcutaneous melittin injection causes central plasticity at the spinal level in wide-dynamic-range (WDR) neurons, which are hypersensitive to various nociceptive stimuli. Previous behavioral studies demonstrated that the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1/2(ERK1/2), p38 MAPK, and c-Jun N-terminal kinase are involved in both peripheral and spinal processing of melittin-induced nociception and hypersensitivity. Yet the functional roles of the three MAPKs vary among different stimulus modalities, and must be further studied at the cellular level in vivo. ⋯ Melittin-induced enhancement of thermal hypersensitivity was also greatly inhibited by a single dose of capsazepine, a thermal nociceptor (TRPV1) blocker. These results suggest that activation of the ERK signaling pathway in the periphery is likely necessary for maintenance of a spinally sensitized state; activation of ERK1/2 in the primary injury site may regulate TRPV1, leading to dorsal horn hypersensitivity to thermal and chemical stimuli. ERK signaling pathways are not likely to be associated with melittin-induced dorsal horn hypersensitivity to mechanical stimuli.
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Brain research bulletin · Nov 2008
Tumor necrosis factor-α of Red nucleus involved in the development of neuropathic allodynia.
The pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) is associated with the generation of inflammatory and neuropathic pain. The current study aims to investigate the expression of TNF-α in the brain of rats with spared nerve injury (SNI), a neuropathic pain model with the lesion of common peroneal and tibial nerves. Two weeks following SNI, the immunohistochemical results identified that the expression level of TNF-α in the Red nucleus (RN) of SNI rats was apparently higher than that of sham-operated rats. ⋯ The results showed that the 50% paw withdrawal threshold (von Frey test) of SNI rats were increased by 20 and 2.0 μg/ml anti-TNF-α antibody as compared with that of the basic value and control groups (P<0.05), the analgesic effect lasted for 50 and 30 min, respectively. However, no significant analgesic effect was observed after 0.2 μg/ml antibody was microinjected into the RN. These results suggest that the TNF-α of RN is involved in the development of neuropathic allodynia in SNI rats.