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• W2528205512 abstract "Background and Purpose Neuropathic pain is under‐treated, with a detrimental effect on quality of life, partly because of low treatment efficacy, but also because pathophysiological mechanisms are not fully elucidated. To clarify the pathobiology of neuropathic pain, we studied the contribution of neuroinflammation and oxidative stress in a model of peripheral neuropathy. We also assessed an innovative treatment for neuropathic pain by investigating the effects of histamine H 4 receptor ligands in this model. Experimental Approach A peripheral mononeuropathy was induced in mice, by spared nerve injury (SNI). Neuroinflammation and oxidative stress parameters were evaluated by spectrophotometry. The mechanical (von Frey test) and thermal (plantar test) nociceptive thresholds were evaluated. Key Results SNI mice showed increased expression of the pro‐inflammatory cytokines IL‐1ß and TNF‐α, decreased antioxidant enzyme Mn‐containing SOD (MnSOD), increased levels of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), an indicator of oxidative DNA damage, and of PARP, nuclear enzyme activated upon DNA damage. Intrathecal administration of VUF 8430 (H 4 receptor agonist) reversed the mechanical and thermal allodynia and was associated with decreased expression of IL‐1ß, TNF‐α, 8‐OHdG and PARP and with restoration of MnSOD activity in the spinal cord and sciatic nerve. These effects were prevented by JNJ 10191584 (H 4 receptor antagonist). Conclusion and Implications In the SNI mouse model of neuropathic pain, neuronal H 4 receptor stimulation counteracts hyperalgesia and reduces neuroinflammation and oxidative stress in the spinal cord and sciatic nerve. Targeting both oxidative stress and pro‐neuroinflammatory pathways through H 4 receptor‐mediated mechanisms could have promising therapeutic potential for neuropathic pain management." @default.
• W2528205512 created "2016-10-14" @default.
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• W2528205512 date "2016-11-18" @default.
• W2528205512 modified "2023-10-06" @default.
• W2528205512 title "Histamine H₄receptor agonist-induced relief from painful peripheral neuropathy is mediated by inhibition of spinal neuroinflammation and oxidative stress" @default.
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• W2528205512 doi "https://doi.org/10.1111/bph.13644" @default.
• W2528205512 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5341487" @default.
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