Pain Sensitivity Assessment Of P75NTR Knockout Mice

Background and Objective:Pain is a physical,psychological and emotional unpleasant feeling,accompanied by the potential or substantial tissue damage of the organism.It is a subjective feeling of the individual.Pain not only affects patients’daily life,social interactions,sleep and emotions,but also brings a range of physical,psychological and social problems.Burn pain refers to the structural muscle function damage caused by burns to the skin,mucous membranes and even deep tissues of the body,resulting in damage to skin receptors and nerve endings,exposure or pathological changes,etc.,as well as during the various treatment operations of burn patients.A variety of unpleasant feelings and experiences.It can directly affect the healing speed and quality of burn wounds,and can also affect the prognosis and outcome of patients.p75NTR is a low-affinity neurotrophic factor receptor that belongs to the tumor necrosis factor(TNF)receptor superfamily and binds to the same series of proteins or coenzymes to mediate the corresponding functions.p75NTR can not only participate in the survival of a variety of neuronal cells,apoptosis and the formation of axon myelination,but also as a helper protein to regulate the response of TrkA receptors.Because the previous experiments mainly studied the interaction of p75NTR and TrkA in skin wound healing,and whether p75NTR can affect the sensitivity of pain and the content of TrkA,there is no clear study.Therefore,in this experiment,mice with p75NTR gene in skin keratinocytes were knocked out,and TrkA was selected as a detection index to observe the differential expression in the skin of knockout mice,and the axon fiber-specific protein PGP9.5 was used as another.A test index was used to observe the changes of nerve fiber content in the skin of knockout mice,to evaluate the sensitivity of knockout mice to pain sensitivity,and to explore the relationship between p75NTR and skin pain and its related mechanisms.Method:8-12w healthy mature wild-free female(WT)and p75NTR knock-out female(KO),weighing 202g,were selected for pain test(hot plate test and acetonetest)to observe the sensitivity of the two groups to pain.Impact,study the pain sensitivity assessment of P75NTR knockout mice.Immunohistochemical staining and Western blot were performed on the skin of wild homozygous mice and knockout mice without any treatment to analyze the differential expression of TrkA protein and PGP9.5 protein in knockout mice.Result:In the hot plate test,the time of the first paw licking of the hind paw was statistically analyzed,indicating that the KO group had a shorter response time to painful contraction caused by noxious thermal stimulation(p<0.001,n=13);The number of times the mouse paws were scratched in the shaved area was statistically analyzed,indicating that the number of pain-scratching reactions caused by noxious cold stimulation was increased in the KO group(p<0.001,n=10);immunohistochemistry showed that p75NTR was mainly expressed in the epidermis.The basal layer is not expressed in the epidermis of KO mice;PGP9.5 protein is scattered in the epidermal base layer and is strongly positive in the epidermis of KO mice;TrkA protein is continuously and evenly distributed in the epidermis,and The expression of KO mouse epidermis increased;Western blot analysis showed that p75NTR protein was not expressed in KO mice(p<0.001,n=9),while TrkA protein expression level was increased(p<0.01,n=9).PGP9.5 protein expression levels were significantly elevated(p<0.001,n = 9).Conclusion:The p75NTR gene was knocked out in the skin of knockout mice;the pain sensitivity of epidermal cells p75NTR knockout mice was increased;the content of nerve fiber terminals in the skin tissue of epidermal cells p75NTR knockout mice increased;the skin of epidermal cells p75NTR knockout mice Increased expression of TrkA in tissues.