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Spinal orexin A attenuates opioid-induced mechanical hypersensitivity in the rat

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Author(s)
Dong-ho YounJiyeon JunTae Wan KimKibeom Park
Keimyung Author(s)
Park, Ki Beom
Department
Dept. of Anesthesiology & Pain Medicine (마취통증의학)
Journal Title
Korean J Pain
Issued Date
2022
Volume
35
Issue
4
Keyword
AnalgesicsOpioidDynorphinsEnkephalinAla(2)-MePhe(4)-Gly(5)-HyperalgesiaOrexinsOrexin ReceptorsPainSpinal Cord Dorsal Horn.
Abstract
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 μg 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.
Keimyung Author(s)(Kor)
박기범
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2093-0569
Source
https://www.epain.org/journal/view.html?doi=10.3344/kjp.2022.35.4.433
DOI
10.3344/kjp.2022.35.4.433
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44478
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anesthesiology & Pain Medicine (마취통증의학)
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