Korean J Pain.  2018 Jul;31(3):174-182. 10.3344/kjp.2018.31.3.174.

Orexin-A inhibits capsaicin-induced changes in cyclooxygenase-2 and brain-derived neurotrophic factor expression in trigeminal nucleus caudalis of rats

• Kooshki R
• Abbasnejad M
• Esmaeili Mahani S
• Raoof M
• Moeini Aghtaei MM
• Dabiri S

• KMID: 2417955
• DOI: http://doi.org/10.3344/kjp.2018.31.3.174

Abstract

BACKGROUND
The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified.
METHODS
Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction.
RESULTS
The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM).
CONCLUSIONS
Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

Keyword

Brain-derived neurotrophic factor (BDRF); Capsaicin; Cyclooxygenase 2 (COX 2); Orexin-A; Orexin receptor antagonists; Orofacial pain; Rats; Pain measurement; Pain perception; Trigeminal caudal nucleus; Trigeminal neuralgia

MeSH Terms

Animals
Brain-Derived Neurotrophic Factor*
Capsaicin
Cyclooxygenase 2*
Facial Pain
Fluorescent Antibody Technique
Injections, Subcutaneous
Lip
Microinjections
Nociceptors
Orexin Receptor Antagonists
Orexins*
Pain Measurement
Pain Perception
Rats*
Trigeminal Caudal Nucleus
Trigeminal Neuralgia
Trigeminal Nuclei*
Brain-Derived Neurotrophic Factor
Capsaicin
Cyclooxygenase 2
Orexin Receptor Antagonists
Orexins

Figure

• 

  Fig. 1 The cannula insertion and the microinjection procedures steps (A) and a coronal section through trigeminal nucleus caudalis (Vc) adapted from the atlas of Paxinos and Watson (B and C). SP5C: spinal trigeminal nucleus caudalis, SP5: spinal trigeminal tract, CC: central canal, PY: pyramidal tract.

• 

  Fig. 2 Schematic drawing of the experimental procedures.

• 

  Fig. 3 Effects of intraVc microinjection of orexin-A (100 pM) and SB-334867-A (80 nM) on capsaicin-induced pain behavior. Data are presented as mean ± SEM (n = 6). ***P < 0.001 versus intact rats, ##P < 0.01, #P < 0.05 versus Caps-treated group, &&&P < 0.001 versus OX-A plus Caps-treated group. Caps: capsaicin, OXA: orexin-A, SB: SB-334867-A.

• 

  Fig. 4 AImmunofluorescence detection of COX-2 in the Vc of rats. A: demonstrating COX-2 staining in Vc cells (green in color), propidium iodide (PI) staining to indicate the nucleus of cells (red in color) and the merged of COX-2 and PI (yellow in color) in intact, capsaicin and capsaicin plus orexin-A (100 pM) or SB-334867-A (80 nM) treated groups. B: statistical comparison of the number of COX-2 positive-cells in Vc sections of experimental groups. Data are presented as mean ± SEM. **P < 0.01, versus intact rats, ##P < 0.01 versus Caps-treated rats, &&P < 0.01 versus OX-A+Caps-treated rats. Caps: capsaicin, OX-A: orexin-A, SB: SB-334867-A.

• 

  Fig. 5 AImmunofluorescence detection of BDNF in the Vc of rats. A: demonstrating BDNF staining in Vc cells (green in color), propidium iodide (PI) staining to indicate the nucleus of cells (red in color) and the merged of BDNF and PI (yellow in color) in intact, capsaicin and capsaicin plus orexin-A (100 pM) or SB-334867-A (80 nM) treated groups. B: statistical comparison of the number of BDNF positive-cells in Vc sections of experimental groups. Data are presented as mean ± SEM. *P < 0.05 versus intact rats, ##P < 0.001 versus Caps-treated rats. Caps: capsaicin, OX-A: orexin-A, SB: SB-334867-A.

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