Sigma-1 Receptor Antagonist, BD1047 Reduces Nociceptive Responses and Phosphorylation of p38 MAPK in Mice Orofacial Formalin Model

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概要

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• Sigma-1 receptors (Sig-1Rs) play a role in different types of pain and in central sensitization mechanism in spinal cord. However, it is currently unexplored whether Sig-1Rs are involved in orofacial pain processing. Here we show whether a selective Sig-1R antagonist, BD1047 reduces nociceptive responses in the mouse orofacial formalin model and the number of Fos-immunoreactive (ir) cells in the trigeminal nucleus caudalis (TNC). In addition, it was examined whether the phosphorylation of extracellular signal-regulated kinase (pERK) or p38 (pp. 38) mitogen-activated protein kinases (MAPK), which are closely linked to pain signaling and sensitization, in TNC was modified by BD1047. The 5% formalin (10 μl) was subcutaneously injected into the right upper lip, and the rubbing responses with ipsilateral fore- or hindpaw were counted for 45 min. BD1047 (1, 3 or 10 mg/kg) were intraperitoneally treated 30 min before formalin injection. High dose of BD1047 (10 mg/kg) produced significant anti-nociceptive effects in the first and the second phase. The number of Fos-ir cells in ipsilateral side of TNC was also reduced by BD1047 as compared to that in saline-treated animals. In addition, the number of pp. 38-ir cells in ipsilateral TNC was decreased in BD1047-treated animals, whereas the number of pERK-ir cells was not modified. Collectively, these results demonstrate that Sig-1Rs play a pivotal role in the orofacial pain processing, and the pp. 38 signaling pathway can be associated with Sig-1R's action in TNC.

著者

• Yoon Seo-Yeon

  Laboratory of Molecular Signal Transduction, Center for Neural Science, Korea Institute of Science and Technology (KIST)

• Roh Dae-Hyun

  Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University

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• Sigma-1 Receptor Antagonist, BD1047 Reduces Nociceptive Responses and Phosphorylation of p38 MAPK in Mice Orofacial Formalin Model

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