title: Sigma-1 receptor antagonist, BD1047 reduces nociceptive responses and phosphorylation of p38 MAPK in mice orofacial formalin model.
abstract: 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 (pp38) 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 hind paw 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 pp38-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 pp38 signaling pathway can be associated with Sig-1R's action in TNC.
authors.affiliation: Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Tissue Regeneration, School of Dentistry, Kyung Hee University.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Roh
authors.forename: Seo-Yeon
authors.initials: SY
authors.lastname: Yoon
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005029:Ethylenediamines / Q000494:pharmacology* / Q000627:therapeutic use; D005157:Facial Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005557:Formaldehyde; D008046:Lip; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D000700:Analgesics; D005029:Ethylenediamines; D005557:Formaldehyde; D016760:Proto-Oncogene Proteins c-fos; D017480:Receptors, sigma; D048051:p38 Mitogen-Activated Protein Kinases; D000097605:Sigma-1 Receptor; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin