Coral-Pérez Santiago, Martínez-Martel Ignacio, Martínez-Serrat Maria, Batallé Gerard, Bai Xue, Leite-Panissi Christie R A, Pol Olga
Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain.
Grup de Neurofarmacologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Antioxidants (Basel). 2022 Oct 30;11(11):2153. doi: 10.3390/antiox11112153.
Chronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinociceptive, antidepressant, and/or anxiolytic actions of H during persistent inflammatory pain have not been investigated. Therefore, using male mice with chronic inflammatory pain incited by the subplantar injection of complete Freud's adjuvant (CFA), we assessed the actions of hydrogen-rich water (HRW) systemically administered on: (1) the nociceptive responses and affective disorders associated and (2) the oxidative (4-hydroxy-2-nonenal; 4-HNE), inflammatory (phosphorylated-NF-kB inhibitor alpha; p-IKBα), and apoptotic (Bcl-2-like protein 4; BAX) changes provoked by CFA in the paws and amygdala. The role of the antioxidant system in the analgesia induced by HRW systemically and locally administered was also determined. Our results revealed that the intraperitoneal administration of HRW, besides reducing inflammatory pain, also inhibited the depressive- and anxiolytic-like behaviors associated and the over expression of 4-HNE, p-IKBα, and BAX in paws and amygdala. The contribution of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1 pathway in the analgesic activities of HRW, systemically or locally administered, was also shown. These data revealed the analgesic, antidepressant, and anxiolytic actions of HRW. The protective, anti-inflammatory, and antioxidant qualities of this treatment during inflammatory pain were also demonstrated. Therefore, this study proposes the usage of HRW as a potential therapy for chronic inflammatory pain and linked comorbidities.
慢性炎症性疼痛在多种疾病中都有表现。分子氢（H₂）作为一种治疗神经疾病的新疗法的潜在用途已得到证实。最近的研究证明了其在患有神经性疼痛的动物中的镇痛特性，但尚未研究H₂在持续性炎症性疼痛期间可能的抗伤害感受、抗抑郁和/或抗焦虑作用。因此，我们使用通过足底注射完全弗氏佐剂（CFA）诱发慢性炎症性疼痛的雄性小鼠，评估了全身给予富氢水（HRW）对以下方面的作用：（1）相关的伤害感受反应和情感障碍，以及（2）CFA在爪子和杏仁核中引发的氧化（4-羟基-2-壬烯醛；4-HNE）、炎症（磷酸化核因子κB抑制因子α；p-IκBα）和凋亡（Bcl-2样蛋白4；BAX）变化。还确定了抗氧化系统在全身和局部给予HRW诱导的镇痛中的作用。我们的结果表明，腹腔注射HRW除了减轻炎症性疼痛外，还抑制了相关的抑郁样和焦虑样行为，以及爪子和杏仁核中4-HNE、p-IκBα和BAX的过度表达。还显示了核因子红细胞2相关因子2/血红素加氧酶1和NAD（P）H：醌氧化还原酶1途径在全身或局部给予HRW的镇痛活性中的作用。这些数据揭示了HRW的镇痛、抗抑郁和抗焦虑作用。还证明了这种治疗在炎症性疼痛期间的保护、抗炎和抗氧化特性。因此，本研究提出将HRW用作慢性炎症性疼痛及其相关合并症的潜在治疗方法。
