Regulation Of TRPM2 On The Development Of Chronic Inflammatory Pain And Neuropathic Pain

Background:Chronic pain is a complex and common clinical condition.It is usually caused by tissue damage or potential tissue damage,which brings inconvenience to people's life and work.There are mainly three manifestations of chronic pain.The first is hyperalgesia,which is enhanced responses to noxious stimulation.The second is allodynia,which is hypersensitivity reactions to non-noxious stimuli.The third is spontaneous pain,the body feels pain which there is no direct irritation.The mechanism of chronic pain is complicated,and many biological proteins are involved in the development of chronic pain.TRPM2(Transient receptor potential melastatin 2,TRPM2)is a non-selective Ca2+-permeable cation channel that participates in the inflammatory responses through intracellular ADPR-dependent and non-ADPR-dependent mechanisms as receptors for ROS/NOD.At present,there are some studies suggest that TRPM2 is involved in the development of acute inflammatory pain and neuropathic pain,but there are few research on the role of TRPM2 on the development of chronic inflammatory pain,and the research of TRPM2 participating in the progression of neuropathic pain is mostly based on sciatic nerve ligation which is very harmful for mice and not an easy skill for researchers to get,The common peroneal nerve ligation model has the advantages of superficial and fixed position,small surgical trauma,simple operation and easy success,It is widely used in pain research.So,this study aimed to clarify whether TRPM2 is involved in the regulation of chronic inflammatory pain and neuropathic pain by using a model of chronic inflammatory pain caused by complete freund's adjuvant and a neuropathic pain model induced by common peroneal nerve ligation.Methods:Firstly,WT mice and TRPM2-KO mice were injected subcutaneously in the left foot with complete Freund's adjuvant for chronic inflammatory pain model.Then,the paw withdrawal threshold was tested with Von Frey filaments indicating mechanical allodynia,and the paw withdrawal latency was tested with a hot tingling instrument indicating heat hyperalgesia.WT mice and TRPM2-KO mice were ligated the left common peroneal nerve for neuropathic pain model,and the same methods was used to test mechanical allodynia and heat hyperalgesia.The lower the 50%paw withdrawal threshold,the more sensitive the mechanical allodynia;the shorter the paw withdrawal latency,the more severe the heat hyperalgesia.Results:The 50%paw withdrawal threshold of the TRPM2 KO-CFA group in the model of chronic inflammatory pain caused by complete Freund's adjuvant was higher compared with the WT-CFA group in day 7 to 21,and the difference reached the maximum in day 21,which was statistically significant(P<0.001);The paw withdrawal latency of the TRPM2 KO-CFA group was longer than that of WT-CFA group(P<0.05)in day 7 and day 21,and the rest was no statistically significant(P>0.05).In the neuropathic pain model induced by the common peroneal nerve ligated,the 50%paw withdrawal threshold of the TRPM2 KO-CPN group was higher than that of the WT-CPN group,and it was statistically significant at day 5(P<0.05)to day 28 after nerve injury;Compared with the WT-CPN group,the TRPM2 KO-CPN group had a longer latency,and the difference was statistically significant(P<0.001)in day 14,which lasted to day 28 after nerve injury.Conclusion:TRPM2 is involved in the regulation of the development of chronic inflammatory pain and neuropathic pain.