The Role Of MTOR Signaling Pathway In Synaptic Plasticity Of The Spinal Dorsal Horn On Neuropathic Pain Rats

Object:In this study,we used the behavior and histology methods to test the pain thresholds of each rat,and to recorde the distribution of mTOR (mammalian target of rapamycin) and AMPA (a-amino-3-hydroxy-5- methylisoxazole-propionate) receptor subunits on the superficial lamella spinal dorsal horn of CCI (chronic constriction injury of the sciatic nerve) rats. In order to determining whether mTOR signaling pathway(s) play an important role during the maintence of neuropathic pain through AMPA receptors,we applicated mTOR special inhibitor rapamycin on CCI rats, and observed the changes of the pain thresholds and the distribution of AMPA receptor subunits.Methods:Twenty-five rats were divided into five groups randomly. The rats in control group were normal rats. The rats in CCI group received an operation of ligation of left sciatic nerve. The rats in shame group received exposure of left sciatic nerve without ligation. The rats in Rapamycin group received intrathecal injection of Rapamycin after CCI.The rats in vehicle group received intrathecal injection of DMSO after CCI.Results:There is no distinction between each group of rats'basic PWMT or PWTL (P>0.05) The rats in shame group and control group have no diversity in PWMT and PWTL test (P>0.05). Contrast to the rats in control group, the PWMT and PWTL of the rats in CCI group significantly attenuation (P<0.05).We also can see signification distinction of PWMT and PWTL between the rats in Rapamycin group and any other groups (P<0.05)。We used immunohistochemistry to show that mTOR and AMPA receptor subunits focuse on the spinal dorsal horn Ⅰ-Ⅲlamellar of rats.The quantity of mTOR and AMPA receptor subunits on rats after CCI was significantly higher than rats in control or shame group. Contrast to DMSO, Rapmycin was potent to reduce the quantity of mTOR and AMPA receptor subunits on spinal horn.Of rats' spinal horn superficial lamellar double-immunostained for glutamate receptor subunits and either marker for mTOR,a significantly large proportion co-express GluR1/2 and mTOR exists.Conclusion:We can conclued that AMPA receptor subunits and mTOR involved in neuropathic pain. Rapmycin is effective to intercept nociception signals transmission and retard the proceduce of neuropathic pain. These observations support the idea that AMPA receptors involved in neuropathic pain,may be modulated by mTOR signaling pathway(s).