Hydrogen-Rich Water Potentiates Cannabinoid- and Gabapentinoid-Induced Analgesia in Neuropathic Pain
Andrea Tort, Nuria (Institut de Recerca Sant Pau)
Negrini Ferrari, Sylmara Esther (Institut de Recerca Sant Pau)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2025
Abstract:	Neuropathic pain (NP) is a complex and disabling condition that often requires long-term treatment with high doses of pharmacological agents, frequently resulting in significant adverse side effects. Therefore, safer and more effective therapeutic approaches are urgently needed. Molecular hydrogen, recognized for its antioxidant and anti-inflammatory actions, may act as a valuable adjunct to conventional analgesics. This study examined whether hydrogen-rich water (HRW) could potentiate the analgesic effects of JWH-133, a selective cannabinoid receptor type 2 agonist, and pregabalin, a gabapentinoid, in male C57BL/6 mice with NP induced by chronic constriction of the sciatic nerve. Mechanical allodynia, thermal hyperalgesia, and cold allodynia were assessed following separate or combined administration of HRW with JWH-133 or pregabalin. Western blot analyses of dorsal root ganglia measured markers of oxidative stress (4-HNE), inflammation (NLRP3), synaptic plasticity (p-ERK), and nociceptive signaling (p-AKT). Each treatment reduced pain-like behaviors in a dose-dependent manner, while co-administration of HRW with JWH-133 or pregabalin produced greater analgesic effects. Combined treatments also diminished oxidative stress, inflammation, maladaptive neural changes and nociceptive pathways activated by peripheral nerve injury. These findings suggest HRW as a promising adjuvant to cannabinoid and gabapentinoid therapies, potentially improving efficacy and reducing high-dose drug-related adverse effects.
Grants:	Instituto de Salud Carlos III PI21/00592
Rights:	Aquesta url de drets no existeix a la base de dades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Analgesia ; Cannabinoids ; Gabapentinoids ; Molecular hydrogen ; Neuropathic pain
Published in:	International journal of molecular sciences, Vol. 26, Num. 24 (December 2025) , art. 12155, ISSN 1422-0067

DOI: 10.3390/ijms262412155
PMID: 41465581

18 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles