| Objective:To study the establishment of a new rat paw inflammatory pain model by intraplantar injection of monosodium iodoacetate(MIA)and the roles of transient receptor potential vanilloid 1(TRPV1)and nerve growth factor(NGF)and its receptor TrkA in the development of the inflammatory pain.Methods:In this study,adult male Wistar rats were randomly divided into control group and groups with different dosages of MIA,with 8 rats in each group.The rats in the control group were injected with 100 μL of normal saline into the sole of the left hind paw,and the rats in the low,medium,and high-dose MIA groups were injected with 100 μL of solutions containing 0.11,0.33,and 1 mg of MIA,respectively.The thermal pain threshold,mechanical pain threshold,dynamic weight bearing and rat paw volume were measured.Rats with MIA-induced inflammatory pain were administered with capsaicin,an agonist of TRPV1,and capsasepine,an antagonist of TRPV1,on the second day after MIA injection to activate and block TRPV1,respectively,to observe the role of TRPV1 in the occurrence and development of MIA-induced inflammatory pain.MIA-induced inflammatory pain rats were administered with K252a,an inhibitor of tyrosine kinase receptor A(TrkA),an NGF receptor for 5 days to block TrkA receptor,so that to observe the role of TrkA in the occurrence and development of MIA-induced inflammatory pain.MIA-induced inflammatory pain rats were given with NGF to activate TrkA on the 2nd day after MIA injection,in order to observe the role of TrkA in the occurrence and development of MIA-induced inflammatory pain.On the 2nd day after the MIA injection,Western blotting was operated to detect the expression levels of TRPV1 proteins in spinal dorsal horn of rats in each group.On the 2nd day after MIA injection,immunohistochemical staining was used to observe the distribution of TRPV1 and TrkA in the paws skin,dorsal root ganglia and spinal dorsal horn of rats.Results:MIA could successfully reduce thermal pain threshold,mechanical pain threshold,and dynamic weight bearing.The hyperalgesia was dose-dependent and lasted for 4-6 days.On the second day after the MIA injection,administration of capsazepine,an inhibitor of TRPV1,could effectively increase the thermal pain threshold,mechanical pain threshold,and dynamic weight bearing,indicating that capsazepine can relieve MIA-induced thermal hyperalgesia,mechanical allodynia and spontaneous pain in rats,and the relief effect was dose-dependent,suggesting that TRPV1 mediates MIA-induced hyperalgesia.After administration of TRPV1 agonist capsaicin,compared with normal rats,the guarding behavior such as paw licking and paw lifting in rats with MIA inflammatory pain increased significantly,indicating that MIA injection may lead to up-regulation of TRP V1 expression in the paw.It is further suggested that TRPV1 mediates MIA-induced hyperalgesia.Western blotting did not detect changes in the expression levels of TRPV1 protein in the spinal dorsal horn of MIA inflammatory pain rats.The above results show that MIA can induce inflammatory pain in rats,and the pain is at least partially mediated by TRPV1,Administration of TrkA inhibitor K252a can effectively increase the thermal pain threshold,mechanical pain threshold,and dynamic weight bearing in rats with MIA-induced inflammatory pain,indicating that K252a can relieve MIA-induced thermal hyperalgesia,mechanical allodynia,and spontaneous pain in rats,suggesting that TrkA receptors mediate MIA-induced hyperalgesia.After administration of NGF,compared with normal rats,the guarding behavior such as paw licking and paw lifting in rats with MIA inflammatory pain were significantly increased,indicating that MIA may up-regulate TrkA expression in the paw.It is further suggested that TrkA receptors mediate MIA-induced hyperalgesia.The above results show that MIA-induced inflammatory pain in rats is mediated at least partially by TrkA receptors.After continuous administration of K252a for three days,compared with normal rats,the capsaicin-induced guarding behavior such as paw licking and paw lifting in rats with MIA inflammatory pain were reduced,indicating TrkA inhibitor can reduce the pain behavior induced by TRPV1 agonist,i.e.that once NGF receptors are inhibited,the function of TRPV1 will be correspondingly reduced,suggesting that NGF and its receptor TrkA mediate MIA-induced hyperalgesia through activating TRPV1,It was observed by immunohistochemical staining that there were coexistence of TRPV1 and TrkA proteins in the same neuron or nerve fiber in the paw skin,dorsal root ganglia,and spinal dorsal horn of rats.Conclusion:(1)The injection of MIA into the rat paw can induce hyperalgesia in the rat,thus creating a new animal model of chronic inflammatory pain.The hyperalgesia can last for 4-6 days.(2)TRPV1 may be involved in mediating MIA-induced hyperalgesia.(3)NGF and its receptor TrkA may be involved in mediating MIA-induced hyperalgesia,(4)NGF and its receptor TrkA may mediate MIA-induced hyperalgesia through activating TRPV1,... |
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