Korean J Physiol Pharmacol.  2009 Dec;13(6):425-429. 10.4196/kjpp.2009.13.6.425.

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

• Kwon YB
• Jeong YC
• Kwon JK
• Son JS
• Kim KW

• KMID: 2285376
• DOI: http://doi.org/10.4196/kjpp.2009.13.6.425

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 immunoreactivity (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.

Keyword

Fos; Headache; N-methyl-D-aspartate receptor; Sigma-1 receptor; Trigeminal nucleus caudalis

MeSH Terms

Animals
Capsaicin
Headache
Migraine Disorders
Models, Animal
N-Methylaspartate
Neurons
Phosphorylation
Rats
Receptors, sigma
Trigeminal Nuclei
Capsaicin
N-Methylaspartate
Receptors, sigma

Figure

• 

  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.

Reference

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