GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model

Background: Peripheral hypersensitivities develop in the face and hindpaws of mice with nitroglycerin (NTG)-induced migraine. We evaluated whether diluted bee venom (DBV) injections at acupoints prevented these peripheral hypersensitivities and c-Fos expression in the trigeminal nucleus caudalis (TN...

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Main Authors: Sol-Ji Kim, Ji-Hee Yeo, Seo-Yeon Yoon, Dae-Hyun Roh
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Integrative Medicine Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213422023000781
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author Sol-Ji Kim
Ji-Hee Yeo
Seo-Yeon Yoon
Dae-Hyun Roh
author_facet Sol-Ji Kim
Ji-Hee Yeo
Seo-Yeon Yoon
Dae-Hyun Roh
author_sort Sol-Ji Kim
collection DOAJ
description Background: Peripheral hypersensitivities develop in the face and hindpaws of mice with nitroglycerin (NTG)-induced migraine. We evaluated whether diluted bee venom (DBV) injections at acupoints prevented these peripheral hypersensitivities and c-Fos expression in the trigeminal nucleus caudalis (TNC). Methods: NTG (10 mg/kg, intraperitoneal, i.p.) was administered every other day for nine days. DBV (0.1 mg/kg) was subcutaneously injected into the ST36 (Zusanli), LI4 (Hegu), or GV16 (Fengfu) acupoints 75 min after each NTG injection. Mice were pretreated with naloxone (5 mg/kg, i.p.) or yohimbine (5 mg/kg, i.p.) 30 min before the DBV injections. Results: NTG injection caused facial cold allodynia, hindpaw mechanical allodynia, and increased c-Fos-immunoreactive (ir) cells in the TNC. Repetitive DBV injections at GV16, but not the ST36, or LI4 acupoints, suppressed NTG-induced hindpaw mechanical allodynia and facial cold allodynia. The number of c-Fos-ir cells also decreased in response to DBV injections at the GV16 acupoint. Remarkably, pretreatment with yohimbine reversed the anti-allodynic effects of DBV injections and attenuated the decreased c-Fos expression in response to GV16 DBV treatment. Naloxone did not block the effects of GV16 DBV stimulation. Conclusion: These findings demonstrate that repetitive DBV treatment at the GV16 acupoint relieves NTG-induced facial and hindpaw hypersensitivities and decreases in c-Fos expression in the TNC via activation of the alpha-2 adrenoceptors, but not the opioid receptors.
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spelling doaj-art-773fe2d423ce40b79ab66e2a9a134b7f2025-08-20T03:35:18ZengElsevierIntegrative Medicine Research2213-42202023-12-0112410099910.1016/j.imr.2023.100999GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse modelSol-Ji Kim0Ji-Hee Yeo1Seo-Yeon Yoon2Dae-Hyun Roh3Department of Oral Physiology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Oral Physiology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Companion Animals, Yuhan University, Bucheon-si, Gyeonggi-do 14780, Republic of Korea; Corresponding authors at: Department of Oral Physiology, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea (D.-H. Roh); Department of Pet Total Care, Division of Business and Fine Art, Daejeon Health Institute of Technology, 21 Chungjeong-ro, Dong-gu, Daejeon 34504, Republic of Korea (S.-Y. Yoon).Department of Oral Physiology, College of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea; Corresponding authors at: Department of Oral Physiology, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea (D.-H. Roh); Department of Pet Total Care, Division of Business and Fine Art, Daejeon Health Institute of Technology, 21 Chungjeong-ro, Dong-gu, Daejeon 34504, Republic of Korea (S.-Y. Yoon).Background: Peripheral hypersensitivities develop in the face and hindpaws of mice with nitroglycerin (NTG)-induced migraine. We evaluated whether diluted bee venom (DBV) injections at acupoints prevented these peripheral hypersensitivities and c-Fos expression in the trigeminal nucleus caudalis (TNC). Methods: NTG (10 mg/kg, intraperitoneal, i.p.) was administered every other day for nine days. DBV (0.1 mg/kg) was subcutaneously injected into the ST36 (Zusanli), LI4 (Hegu), or GV16 (Fengfu) acupoints 75 min after each NTG injection. Mice were pretreated with naloxone (5 mg/kg, i.p.) or yohimbine (5 mg/kg, i.p.) 30 min before the DBV injections. Results: NTG injection caused facial cold allodynia, hindpaw mechanical allodynia, and increased c-Fos-immunoreactive (ir) cells in the TNC. Repetitive DBV injections at GV16, but not the ST36, or LI4 acupoints, suppressed NTG-induced hindpaw mechanical allodynia and facial cold allodynia. The number of c-Fos-ir cells also decreased in response to DBV injections at the GV16 acupoint. Remarkably, pretreatment with yohimbine reversed the anti-allodynic effects of DBV injections and attenuated the decreased c-Fos expression in response to GV16 DBV treatment. Naloxone did not block the effects of GV16 DBV stimulation. Conclusion: These findings demonstrate that repetitive DBV treatment at the GV16 acupoint relieves NTG-induced facial and hindpaw hypersensitivities and decreases in c-Fos expression in the TNC via activation of the alpha-2 adrenoceptors, but not the opioid receptors.http://www.sciencedirect.com/science/article/pii/S2213422023000781Bee venomNitroglycerinAllodyniaFosAlpha-2 adrenoceptors
spellingShingle Sol-Ji Kim
Ji-Hee Yeo
Seo-Yeon Yoon
Dae-Hyun Roh
GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
Integrative Medicine Research
Bee venom
Nitroglycerin
Allodynia
Fos
Alpha-2 adrenoceptors
title GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
title_full GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
title_fullStr GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
title_full_unstemmed GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
title_short GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model
title_sort gv16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin induced migraine mouse model
topic Bee venom
Nitroglycerin
Allodynia
Fos
Alpha-2 adrenoceptors
url http://www.sciencedirect.com/science/article/pii/S2213422023000781
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