The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats

Abstract

Aim To explore the role of P2Y6 receptors in the maintenance of neuropathic pain and progression of oxidative stress, we investigated the efficacy of the selective P2Y6 receptors antagonist MRS2578 on the antiallodynic effects and improvement of pathological neuropathic pain‐induced oxidative stress, thereby finding a potential therapeutic target in neurological disease. Materials and Methods The mechanical allodynia in the ipsilateral spinal dorsal horn (SDH) of rats was observed in rats after chronic constriction injury (CCI). Meanwhile, the messenger RNA (mRNA) levels of biological parameters, including superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase‐1 (HO‐1) in the SDH of rats were measured by real‐time polymerase chain reaction (RT‐PCR). In addition, the mRNA expression and protein levels of P2Y6 were measured by RT‐PCR and Western blot assay, respectively. Next, the rats subjected to CCI were intrathecally infused with MRS2578 to block the expression of P2Y6 receptors. The positive expression of P2Y6 receptors was examined by immunohistochemistry. Results In the present study, the results revealed that the P2Y6 expression in the ipsilateral SDH of CCI rats was significantly upregulated. In addition, inhibition of the P2Y6 receptor in SDH increased CCI‐induced tactile allodynia. Furthermore, the levels of SOD, GSH, and HO‐1 which were correlated with oxidative stress produced by CCI were also decreased. Conclusion The results demonstrated that inhibition of the P2Y6 receptor can generate antiallodynic effects and improved the pathological neuropathic pain‐induced oxidative stress. Thus, this study provides a potential approach for the therapy of neurological disease.

Artificial Neural Networks Coupled with MALDI-TOF MS Serum Fingerprinting To Classify and Diagnose Pathological Pain Subtypes in Preclinical Models

“…Changes in low-molecular-weight molecule expression have been reported as possibly being involved in different types of pathological pain. For instance, a decline in antioxidant molecules such as glutathione (307 Da) induces mechanical allodynia and thermal hyperalgesia after CCI, − the l -lactate (89 Da) overload resulting from aberrant spinal astrocyte neuron lactate shuttle, has been associated with neuropathic pain maintenance, and levels of tetrahydrobiopterin (BH4; 241 Da) are dramatically increased in sensory neurons after peripheral nerve damage increasing pain hypersensitivity. , …”

Pre-emptive PPAR-γ Activation Abolishes Development of Nerve Injury-induced Behavioral Hypersensitivity: Elucidating Underlying Mechanisms

“…Recent evidence suggests that nuclear factor-erythroid 2-related factor/antioxidant responsive element (NRF2/ARE) and PPAR-γ/PPAR-γ response element (PRE) pathways regulate redox signaling and the underlying mechanisms to control oxidative stress, inflammation and overcome mitochondrial impairment [37,38]. Indeed, synthetic and natural agents that abrogate nitroso-oxidative stress and free radical scavengers were well reported to inhibit neuropathic pain [34,[38][39][40][41]. It is possible that pioglitazone activated antioxidant mechanisms might be contributed to attenuate the development of neuropathic pain and sustained long-term effects and such protective effects were abolished by PAPR-γ antagonist BADGE in ipsilateral paws of mononeuropathic rats.…”

Thiol/Disulfide Balance in Induced Phenylketonuria Model

“…There has been no prior study on the thiol/disulfide balance reported, but the relationship of PKU with many original oxidative stress parameters has been evaluated in the literatüre [9][10][11][12][13][14]. We examined how it affects the thiol/disulfide balance in PKU in our study.…”