Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain

Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investi...

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Main Authors: Zhen Shen (Author), Yun-Dan Guo (Author), Ming-Ze Tang (Author), Ping Zhou (Author), Yu-Xin Su (Author), Hao-Ran Shen (Author), Tao Li (Author), Wei Jiang (Author), Yan-Xing Han (Author), Cai Tie (Author), Jing-Jing Cui (Author), Tian-Le Gao (Author), Jian-Dong Jiang (Author)
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Published: MDPI AG, 2024-07-01T00:00:00Z.
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100 1 0 |a Zhen Shen  |e author 
700 1 0 |a Yun-Dan Guo  |e author 
700 1 0 |a Ming-Ze Tang  |e author 
700 1 0 |a Ping Zhou  |e author 
700 1 0 |a Yu-Xin Su  |e author 
700 1 0 |a Hao-Ran Shen  |e author 
700 1 0 |a Tao Li  |e author 
700 1 0 |a Wei Jiang  |e author 
700 1 0 |a Yan-Xing Han  |e author 
700 1 0 |a Cai Tie  |e author 
700 1 0 |a Jing-Jing Cui  |e author 
700 1 0 |a Tian-Le Gao  |e author 
700 1 0 |a Jian-Dong Jiang  |e author 
245 0 0 |a Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain 
260 |b MDPI AG,   |c 2024-07-01T00:00:00Z. 
500 |a 10.3390/antiox13070803 
500 |a 2076-3921 
520 |a Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin's analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin's efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin's analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation-key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy. 
546 |a EN 
690 |a chronic pain 
690 |a combination therapy 
690 |a neuroinflammation 
690 |a HMGB1 
690 |a ATP 
690 |a Nrf2 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Antioxidants, Vol 13, Iss 7, p 803 (2024) 
787 0 |n https://www.mdpi.com/2076-3921/13/7/803 
787 0 |n https://doaj.org/toc/2076-3921 
856 4 1 |u https://doaj.org/article/9febe5dd4fbf4ef28cdd72c6afec79b9  |z Connect to this object online.