The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Young Bae Kwon; Young Chan Jeong; Jung Kee Kwon; Ji Seon Son; Kee Won Kim

doi:10.4196/kjpp.2009.13.6.425

Journal List > Korean J Physiol Pharmacol > v.13(6) > 1025637

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Kwon, Jeong, Kwon, Son, and Kim: The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Original Article

Korean J Physiol Pharmacol 2009;13(6):425-429.

Published online: 18 February 2009

DOI: https://doi.org/10.4196/kjpp.2009.13.6.425

The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats

Young Bae Kwon¹, Young Chan Jeong¹, Jung Kee Kwon², Ji Seon Son³, Kee Won Kim^1,

¹Department of Pharmacology, College of Medicine, Chonbuk National University, Jeonju 561-180, Korea

²Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-180, Korea

³Department of Anesthesiology and Pain Medicine, College of Medicine, Chonbuk National University, Jeonju 561-180, Korea

Corresponding to: Kee Won Kim, Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju 561-180, Korea. (Tel) 82-63-270-3090, (Fax) 82-63-275-2855, (E-mail) keewon222@gmail.com

Received 6 October 2009 Revised 4 November 2009 Accepted 12 November 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunore-activity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

Keywords: Fos, Headache, N-methyl-D-aspartate receptor, Sigma-1 receptor, Trigeminal nucleus caudalis

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Fig. 1.

The time spent on face grooming behavior within 10 minutes after capsaicin infusion (2.5 nmol/rat). BD1047 was introduced 10 min prior to capsaicin infusion. ^∗∗p<0.01 compared to vehicle control group (first column). ^#p<0.05, ^##p<0.01 compared to capsaicin group (second column). Each group contains 6 animals.

Fig. 2.

Fos-like immunoreactivity (Fos-LI) in the trigeminal nucleus caudalis (TNC) at 2 hours after intracisternal drug infusion. (A) Vehicle (artificial CSF) control, (B) capsaicin (2.5 nmol), (C) capsaicin (Cap, 2.5 nmol)+BD1047 (BD, 100 nmol). Scale bar=200 μm.

Fig. 3.

Number of Fos-like immunoreactive (Fos-LI) neurons in the trigeminal nucleus caudalis (TNC) at 2 hours after intracisternal capsaicin or vehicle infusion. BD1047 was introdced 10 min prior to capsaicin infusion. ^∗∗p<0.01 compared to vehicle control group (first column). ^#p<0.05, ^##p<0.01 compared to capsaicin group (second column). Each group contains 6 animals.

Fig. 4.

The phosphorylation of NMDA-receptor subunit 1 (pNR1) positive immunoreactivity in the trigeminal nucleus caudalis (TNC) at 2 hours after intracisternal drug infusion. (A) Vehicle (artificial CSF) control, (B) capsaicin (2.5 nmol), (C) capsaicin (Cap, 2.5 nmol)+BD1047 (BD, 100 nmol). Scale bar=200 μm.

Fig. 5.

The phosphorylation of NMDA-receptor subunit 1 (pNR1) immunoreactivity in the trigeminal nucleus caudalis (TNC) at 2 hours after intracisternal capsaicin or vehicle infusion. BD1047 was introduced 10 min prior to capsaicin infusion. ^∗p<0.05, ^∗∗p<0.01 compared to vehicle control group (first column). ^#p<0.05, ^##p<0.01 compared to capsaicin group (second column). Each group contains 6 animals.

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