COVID-19 Coronavirus Research Tools
Pre-Made AAVs Center
Neuronal Tracing Tool

BrainVTA

Construction and Packaging Service of virus Vector

Construction and Packaging Services of AAV

Large scale AAV production

GPR151 in nociceptors modulates neuropathic pain via regulati
AAV9-sgRNA was used for gene Gpr151 knockout. (From BrainVTA)
The viruses used in this article from BrainVTA are in the table below
Custom-Made AAV  AAV9-sgRNA
Li-Ping Xia, Hao Luo, Qiang Ma, Ya-Kai Xie, Wei Li, Hailan Hu, Zhen-Zhong Xu
Pub Date: 2021-07-05, DOI: 10.1093/brain/awab245, Email: [email protected]
Neuropathic pain is a major health problem that affects up to 7–10% of the population worldwide. Currently, neuropathic pain is difficult to treat because of its elusive mechanisms. Here we report that orphan G protein-coupled receptor 151 (GPR151) in nociceptive sensory neurons controls neuropathic pain induced by nerve injury. GPR151 was mainly expressed in non-peptidergic C-fibre dorsal root ganglion neurons and highly upregulated after nerve injury. Importantly, conditional knockout of Gpr151 in adult nociceptive sensory neurons significantly alleviated chronic constriction injury-induced neuropathic pain-like behaviour but did not affect basal nociception. Moreover, GPR151 in DRG neurons was required for chronic constriction injury-induced neuronal hyperexcitability and upregulation of colony-stimulating factor 1 (CSF1), which is necessary for microglial activation in the spinal cord after nerve injury. Mechanistically, GPR151 coupled with P2X3 ion channels and promoted their functional activities in neuropathic pain-like hypersensitivity. Knockout of Gpr151 suppressed P2X3-mediated calcium elevation and spontaneous pain behaviour in chronic constriction injury mice. Conversely, overexpression of Gpr151 significantly enhanced P2X3-mediated calcium elevation and dorsal root ganglion neuronal excitability. Furthermore, knockdown of P2X3 in dorsal root ganglia reversed chronic constriction injury-induced CSF1 upregulation, spinal microglial activation and neuropathic pain-like behaviour. Finally, the coexpression of GPR151 and P2X3 was confirmed in small-diameter human dorsal root ganglion neurons, indicating the clinical relevance of our findings. Together, our results indicate that GPR151 in nociceptive dorsal root ganglion neurons plays a key role in the pathogenesis of neuropathic pain and could be a potential target for treating neuropathic pain.

Figure 1. Proposed model for the role of GPR151 in neuropathic pain via regulating P2X3 function and microglial activation.
In this study, the authors demonstrate that GPR151 is expressed mainly in non-peptidergic C-fibre DRG neurons and plays a key role in the pathogenesis of neuropathic pain. Microglial activation in the spinal cord is important for both the initiation and maintenance of neuropathic pain. Thus, the data indicate that targeting GPR151 in DRG neurons could be a promising therapeutic strategy for treating neuropathic pain.
 
BrainVTA offers viral vector construction & virus packaging services for AAV, LV, RABV, PRV, HSV and VSV that help researchers explore questions about genes, neurons, circuitry structure, function of brain network, mechanism and treatment of diseases.
If you have any needs, just email us at [email protected].



50% discount for Pre-Made AAVs