• Meng-Meng Li, Yao-Qing Yu, Han Fu, Fang Xie, Li-Xian Xu, and Jun Chen.
• Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, #1 Xinsi Road, Baqiao, Xi'an 710038, PR China.
• Brain Res. Bull. 2008 Nov 25;77(5):227-32.

AbstractSubcutaneous 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. In this report, extracellular single unit recordings were performed to investigate whether activation of ERK1/2 in the primary injury site of melittin is essential to the establishment of a spinally sensitized state. Localized peripheral administration of a single dose of the MEK inhibitor U0126 (1 μg/10 μl) significantly suppressed neuronal hyper-responsiveness to thermal stimulus and chemical (melittin)-induced tonic firing of WDR neurons after full establishment of a spinally sensitized state. However, U0126 failed to affect mechanical hypersensitivity to both noxious and non-noxious stimuli. 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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