Neferine alleviates P2X3 receptor in rat dorsal root ganglia mediated neuropathic pain

Yu, Dan; Guo, Hongmin; Zheng, Chaoran; Wu, Baoguo; Guo, Jingjing; Li, Guilin

doi:10.1016/j.neures.2020.08.004

Cited by 10 publications

(5 citation statements)

References 59 publications

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“…Highdose KN93 (50 nmol) reduced p-CaMKIIα and P2X3 levels in DRGs. The latter is widely implicated in neuropathic pain [52][53][54] and DNP. Thus, p-CaMKIIα may influence DNP by modulating P2X3 expression in DRGs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

Kang

Fei

et al. 2022

Purinergic Signalling

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Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.

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Section: Discussionmentioning

confidence: 99%

Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

Kang

Fei

et al. 2022

Purinergic Signalling

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“…Finally, the membrane was subjected to exposure with hypersensitive ECL luminescent solution (FD8020; Fude Biotechnology Co., Ltd, Hangzhou, China) and signal detection. The integrated optical density (IOD) values of the detected proteins were analyzed by Image-Pro Plus software (Media Cybernetics Inc., Rockville, MD) ( Dan et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

The P2X7 Receptor Is Involved in Diabetic Neuropathic Pain Hypersensitivity Mediated by TRPV1 in the Rat Dorsal Root Ganglion

Wang

Shi

et al. 2021

Front. Mol. Neurosci.

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The purinergic 2X7 (P2X7) receptor expressed in satellite glial cells (SGCs) is involved in the inflammatory response, and transient receptor potential vanilloid 1 (TRPV1) participates in the process of neurogenic inflammation, such as that in diabetic neuropathic pain (DNP) and peripheral neuralgia. The main purpose of this study was to explore the role of the P2X7 receptor in DNP hypersensitivity mediated by TRPV1 in the rat and its possible mechanism. A rat model of type 2 diabetes mellitus-related neuropathic pain (NPP) named the DNP rat model was established in this study. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of DNP rats were increased after intrathecal injection of the P2X7 receptor antagonist A438079, and the mRNA and protein levels of TRPV1 in the dorsal root ganglion (DRG) were decreased in DNP rats treated with A438079 compared to untreated DNP rats; in addition, A438079 also decreased the phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) in the DNP group. Based on these results, the P2X7 receptor might be involved in DNP mediated by TRPV1.

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“…PKC phosphorylation in the primary nociceptive neurons is thought to upregulate P2X 3 receptor expression through nuclear factor-kappa B signaling and potentiate P2X 3 receptor activity (Li et al, 2020;Wang et al, 2012). In previous reports, sciatic nerve injury induced plantar mechanical allodynia and increased P2X 3 receptor expression in sensory neurons, which were inhibited by neferine administration (Dan et al, 2021). In the orofacial region, ovariectomy significantly decreased the orofacial mechanical pain threshold and increased P2X 3 mRNA expression in the TG that was inhibited by estrogen replacement (Yu et al, 2011).…”

Section: Channels Formed With Half Of the Gap Junction Components And...mentioning

confidence: 97%

Pannexin 1 role in the trigeminal ganglion in infraorbital nerve injury‐induced mechanical allodynia

et al. 2022

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Objectives The detailed pathological mechanism of orofacial neuropathic pain remains unknown. We aimed to examine the pannexin 1 (Panx1) signaling in the trigeminal ganglion (TG) involvement in infraorbital nerve injury (IONI)‐induced orofacial neuropathic pain. Materials and Methods Mechanical head‐withdrawal threshold (MHWT) was measured in IONI‐treated rats receiving intra‐TG Panx1 inhibitor or metabotropic glutamate receptor 5 (mGluR5) antagonist administration and MHWTs in naive rats receiving intra‐TG mGluR5 agonist administration post‐IONI. Glutamate and Panx1 in the TG were measured post‐IONI. Panx1, mGluR5, and glutamine synthetase expression in TG were immunohistochemically identified, and changes in the number of mGluR5‐P2X3‐expressed TG neurons were examined. Results MHWT was significantly decreased post‐IONI, and this decrease was reversed by Panx1 inhibition or mGluR5 antagonism. mGluR5 agonism induced a decrease in the MHWT. IONI increased extracellular glutamate in TG. Panx1 was expressed in satellite glial cells and TG neurons, and intra‐TG mGluR5 antagonism decreased the number of mGluR5 and P2X3 positive TG neurons post‐IONI. Conclusions IONI facilitates glutamate release via Panx1 that activates mGluR5 which was expressed in the nociceptive TG neurons innervating the orofacial region. In turn, P2X3 receptor‐expressed TG neurons are enhanced via mGluR5 signaling, resulting in orofacial neuropathic pain.

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Neferine alleviates P2X3 receptor in rat dorsal root ganglia mediated neuropathic pain

Cited by 10 publications

References 59 publications

Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

The P2X7 Receptor Is Involved in Diabetic Neuropathic Pain Hypersensitivity Mediated by TRPV1 in the Rat Dorsal Root Ganglion

Pannexin 1 role in the trigeminal ganglion in infraorbital nerve injury‐induced mechanical allodynia

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