The Endogenous Opioids Related with Antinociceptive Effects Induced by Electrical Stimulation into the Amygdala

Takami Nakamura 1, 2, *, Mihoko Tomida 2, Toshiharu Yamamoto 3, Hiroshi Ando 2, Tetsuya Takamata 1, Eiji Kondo 4, Ikufumi Kurasawa 5, Naokazu Asanuma 2
1 Department of Oral and Maxillofacial Biology, Graduate School of Oral Medicine, Matsumoto Dental University, Japan
2 Department of Oral Physiology, Matsumoto Dental University, Japan
3 Department of Human Biology, Kanagawa Dental College, Japan
4 Department of Oral Anatomy, Matsumoto Dental University, Japan
5 Department of Prosthetic Dentistry, Matsumoto Dental University, Japan

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© Nakamura et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Oral Physiology, Matsumoto Dental University, 1780 Hirooka-Gobara, Shiojiri, 399-0781 Japan; Tel/Fax: +81-263-51-2053; E-mail:


Pain relief is necessary and essential for dental treatments. Recently, the relationships of pain and emotion were studied, and electrical stimulation applied to the amygdala depressed the nociceptive response in the anterior cingulate cortex (ACC). Thus, the antinociceptive effects of the amygdala are elucidated, but its mechanism is not yet clarified. The present study was performed to investigate whether endogenous opioid system is related to the depression, and the quantitative changes of endogenous opioids induced by electrical stimulation to the amygdala. We investigated immunohistologically c-Fos expression to confirm the activated neurons, as well as the distribution and the amount of endogenous opioids (β-endorphin, enkephalin and dynorphin A) in the brain using male Wistar rats, when electrical stimulation was applied to the central nucleus of the amygdala (CeA) or noxious stimulation was delivered to the peripheral tissue. c-Fos expression in the ipsilateral ACC was increased by electrical stimulation to the CeA. However, only a small amount of endogenous opioids was observed in the ACC when noxious stimulation or electrical stimulation was applied. In contrast, the amount of dynorphin A in the periaqueductal gray (PAG) was increased by electrical stimulation to the CeA, and the amount of β-endorphin in the PAG was increased by noxious stimulation to the peripheral tissue. The results suggest that dynorphin A in the PAG induced by electrical stimulation to the CeA activate the descending antinociceptive system, and suggest that the nociceptive response in the ACC is depressed indirectly.

Keywords: Amygdala, anterior cingulate cortex, β-endorphin, enkephalin, dynorphin A, periaqueductal gray.