| Diabetic neuropathic pain(DNP)is one of the common complications caused by type I / type II diabetes mellitus(T1DM/T2DM).It is characterized by mechanical induced ectopic pain and abnormal pain and anaphylaxis caused by harmless stimulation.Up to now,there is no specific treatment.Mrgc receptor is specifically distributed in the peripheral nervous system and plays an analgesic role in pathological pain caused by nerve injury,inflammation,cancer and morphine tolerance.It is an ideal drug intervention target.However,it is not clear whether activating MrgC receptor can alleviate diabetic neuropathic pain.In this study,we established the type I / type II diabetic neuropathic pain model(T1/2 DNP)by intraperitoneal injection of streptozotocin(STZ).We used behavioral,q RT-PCR,Western Blot and tissue immunofluorescence techniques to explore the effect and mechanism of MrgC receptor activation on rat DNP.The experimental results are as follows:(1)60mg/kg STZ can be successfully established in type I diabetic neuropathic pain model(T1 DNP)by single intraperitoneal injection.After 4 weeks of high fat diet,STZ(35 mg/kg)was injected intraperitoneally to establish a type II diabetic neuropathic pain model(T2 DNP).(2)On the 28 th day after STZ induced DNP,the expression of MrgC m RNA in dorsal root ganglion(DRG)decreased significantly.After intrathecal injection of MrgC receptor specific agonist BAM8-22(5 nmol,10 nmol,15 nmol),the decreased mechanical pain threshold caused by DNP increased significantly,and the pain inhibition effect was the best when the dose was 10 nmol.30 min after intrathecal injection of BAM8-22,the mechanical pain threshold of T2 DNP rats reached the highest point;60min after intrathecal injection of BAM8-22,the mechanical pain threshold of T1 DNP rats reached the highest point,indicating that intrathecal injection of BAM8-22 to activate MrgC receptor can alleviate STZ induced DNP.(3)On the 28 th day after STZ induced DNP,the expressions of GFAP,TNF-α and IL-1β in DRG of T1/2 DNP rats increased significantly,the expressions of Neu N and Na V1.7 increased significantly,and the expression of IGF-1 decreased significantly.After intrathecal injection of 10 nmol BAM8-22,the above phenomena were significantly reversed,indicating that the activation of MrgC receptor can reduce rat DNP by regulating the interaction between satellite glial cells and neurons in DRG.IGF-1 and IGF-1R in DRG are co expressed with satellite glial cells(GFAP)and neurons(Neu N),suggesting that IGF-1 may play an intermediate "bridge" role in the interaction between MrgC receptor regulated neurons and satellite glial cells to alleviate DNP.(4)On the 28 th day after STZ induced DNP,the expression of GFAP increased significantly,Ca V3.2 expression increased significantly and the expression of IGF-1decreased significantly in the spinal dorsal horn(SDH)of T1/2 DNP rats.After intrathecal injection of 10 nmol BAM8-22,the above phenomena were significantly reversed.The results show that activated MrgC receptor can reduce rat DNP by regulating the interaction between astrocytes and neurons in rat SDH.IGF-1 and IGF-1R in SDH were co expressed with satellite glial cells(GFAP)and neurons(Neu N),suggesting that the expression of IGF-1 plays an important role in relieving DNP by regulating the interaction between neurons and astrocytes after MrgC receptor activation.In conclusion,activation of MrgC receptor can effectively inhibit STZ induced DNP in rats.The activated MrgC receptor can regulate the interaction between neurons and satellite glia,neurons and astrocytes and alleviate rat DNP through IGF-1. |
