The Korean Journal of Pain

  • 제35권4호
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  • Pages.433-439
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  • 2022
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  • 2005-9159(pISSN)
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  • 2093-0569(eISSN)
대한통증학회 (The Korean Pain Society)
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Spinal orexin A attenuates opioid-induced mechanical hypersensitivity in the rat

  • Youn, Dong-ho (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Jun, Jiyeon (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Kim, Tae Wan (Department of Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Kibeom (Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine)
  • 투고 : 2022.05.06
  • 심사 : 2022.08.09
  • 발행 : 2022.10.01
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초록

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). Methods: [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 ㎍ for all). Mechanical hypersensitivity was assessed using von Frey monofilaments. Results: Repeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity. Conclusions: Spinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

키워드

과제정보

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2019R1F1A1062761).

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