Intra-periaqueductal gray matter administration of orexin-A exaggerates pulpitis-induced anxiogenic responses and c-fos expression mainly through the interaction with orexin 1 and cannabinoid 1 receptors in rats

A.M. Pourrahimi, M. Abbasnejad, S. Esmaeili-Mahani, R. Kooshki, M. Raoof

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Different types of trigeminal pains are frequently associated with psychophysiological concerns. Orexin-A and orexin 1 receptor (OX1R) are involved in modulation of both trigeminal pain and anxiety responses. Ventrolateral periaqueductal gray matter (vlPAG), a controlling site for nociception and emotion, receives orexinergic inputs. Here, the role of vlPAG OX1Rs and their interaction with cannabinoid 1 (CB1) receptor was evaluated in anxiety-like behavior following capsaicin-induced dental pulp pain. Rats were cannulated in the vlPAG and orexin-A was injected at the doses of 0.17, 0.35 and 0.51 μg/rat prior to the induction of pain. The elevated plus maze (EPM) and open field (OF) tests were used for assessing the anxiety responses. In addition, the induction of c-fos, in the vlPAG, was investigated using immunofluorescence microscopy. Capsaicin-treated rats displayed significantly higher anxiogenic behavior on EPM and OF tests. Pretreatment with orexin-A (0.51 μg/rat) attenuated capsaicin-mediated nociception, while exaggerated anxiogenic responses (p < 0.05). In addition, orexin-A effects were diminished by the administration of OX1R (SB-334867, 12 μg/rat) and cannabinoid 1 (AM251, 4 μg/rat) receptor antagonists. Intradental capsaicin induced a significant increase in c-fos expression in the vlPAG that was exaggerated by orexin-A (0.51 μg/rat). Blockage of OX1R and CB1 receptors attenuated the effect of orexin-A on c-fos expression in capsaicin-treated rats. In conclusion, the data suggest that manipulation of OX1R and CB1 receptors in the vlPAG alters capsaicin-evoked anxiety like behaviors and c-fos induction in rats.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalNeuropeptides
Volume73
DOIs
Publication statusPublished - Feb 2019

Funding

The authors wish to thank Kerman Neuroscience Research Center for financial support and Ms. Emma Tait who took the burden of proof reading of the article.

FundersFunder number
Kerman Neuroscience Research Center

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