Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

Abstract

Reactive oxygen species (RoS) are involved in the development of pains in various conditions, including neuropathic and inflammatory pain [1][2][3][4][5] . Park et al reported increased RoS in the spinal cord of rats after peripheral nerve injury 6 . others found that treatment with RoS scavengers phenyl Ntert-butylnitrone (PbN), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tEMPoL), 5,5-dimethylpyrroline -N-oxide (DMPo) or vitamin E could temporarily reverse the allodynia developed after nerve ligation in rats 2,7,8 . the function mechanisms of RoS scavenger, like that of PbN-induced analgesic effect, are reported to be mediated mainly via spinal mechanisms 2 .ABSTRACT: Background: Reactive oxygen species (RoS) are often associated with persistent pains such as neuropathic and inflammatory pain. Hydrogen gas can reduce RoS and alleviate cerebral, myocardial, and hepatic ischemia/reperfusion injuries. in the present study, we aim to investigate whether hydrogen-rich saline can reduce neuropathic pain in a rat model of chronic constriction injury (CCi). Methods: thirty SD rats were randomly divided into three groups: sham group was administered sodium chloride by intrathecal injection (n=10); control groups underwent CCi surgery and were administered sodium chloride by intrathecal injection (n=10); vehicle group underwent CCi surgery and was administered hydrogen-rich saline by intrathecal injection (n=10). Drugs were administered in the dose of 100ul/kg once a day at 0.5 hours before and 1-7 day after CCi surgery. the mechanical thresholds were tested at one day before and 3-14 day after CCi surgery. Results: We found that hydrogen-rich saline significantly elevated the mechanical thresholds of neuropathic pain compared to vehicle (physiologic saline) control in CCi rats (p<0.05); it also decreased the levels of myeloperoxidase, maleic dialdehyde, and protein carbonyl in spinal cord by 7 days post-chronic constriction injury(p<0.05). in addition, hydrogen-rich saline also suppressed the expression of p38-mitogen-activated protein kinase (p38MAPK) and brain-derived neurotrophic factor (bDNF) in the spinal cord by 7 days post-chronic constriction injury (p<0.01, p<0.01, respectively), but had no effect on P2X4R (p>0.05), an AtP receptor. Conclusion: intrathecal injection of hydrogen-rich saline can decrease oxidative stress and the expression of p38MAPK and bDNF that may contribute to the elevated threshold of neuropathic pain in rat CCi model. RÉSUMÉ:Le salin riche en hydrogène atténue la douleur névropathique en réduisant le stress oxydatif. Contexte : Les espèces réactives oxygénées (RoS) sont souvent associées à la douleur persistante comme la douleur névropathique et la douleur inflammatoire. Le gaz hydrogène peut réduire les RoS et soulager le dommage dû à l'ischémie/la reperfusion au niveau cérébral, myocardique et hépatique. Le but de cette étude était de déterminer si le salin riche en hydrogène peut réduire la douleur névropathique chez un modèle de lésion par constriction chronique (LCC) chez le rat. ...

Molecular Hydrogen Attenuates Neuropathic Pain in Mice

“…Recently, it was reported that intrathecal administration of hydrogen-rich saline relieve neuropathic pain induced by CCI in rats [22]. This accord with our study and further support the possibility of therapeutic use of hydrogen in pain medicine.…”

H2Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain

“…Growing research and our previous studies have also shown the protective and preventive effects of H 2 in sepsis, MODS, LPS-induced acute lung injury, neuropathic pain, etc., without remarkable side effects, by reducing inflammation response, apoptosis, and oxidative stress [13][14][15][16][17][18]. In this study, neuropathic pain was induced by chronic constriction of sciatic nerve, which contributed to the development of both hyperalgesia and allodynia.…”

“…Hydrogen has been reported to play a vital therapeutic role in sepsis, multiple organ dysfunction syndrome (MODS), lipopolysaccharide (LPS)-induced acute lung injury (ALI), and chronic pain, among others, through its anti-apoptosis effect, alleviating excessive inflammatory response and oxidative stress [13][14][15][16][17][18]. This strongly implies that hydrogen (H 2 ) treatment has beneficial and anti-inflammatory effects.…”

The transfer of hydrogen from inert gas to therapeutic gas

“… 33 Besides, HRS could improve the mechanical threshold of neuropathic pain in a rat model of chronic constriction injury, which possibly by reducing oxidative stress and the subsequent expression of p38 MAPK and brain-derived neurotropic factor. 34 In a controlled cortical impact model, HRW totally blocked the elevations of phosphorylated tau both in hippocampal and cortical regions, thus protected against neurodegenerative changes. 35 Moreover, it has been further clarified that HRW treatment decreased pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels using the same model.…”