Abstract:

Objective To explore the mechanism of neuropathic pain suppression by activating metabotropic glutamate receptor 4 (mGluR4). Methods Firstly, 24 SD rats were randomly divided into blank control group (n=6), shame operation group (n=6), and SNL group (n=12) after intrathecal catheterization. Rats in control group were only undergone the intrathecal catheterization. Values of 50%PWT were measured for other rats before surgery and 1~6 d after surgery. Then, rats in SNL group were randomly divided into SNL+saline group (n=6) and SNL+VU0155041 group (n=6) and received intrathecal injection of saline and VU0155041(500 nmol) 10 μL twice a day for seven days, respectively. Values of 50%PWT were measured before injection and 30 min after injection. Finally, left spinal dorsal horn of the spinal enlargement of control group, SNL+saline group and SNL+VU0155041group were obtained 1h after last injection and submitted for gene chip examination. The expression of mGluR4 and the subtypes of Rab5 were determined by Western blotting. Results During 1~6 d after surgery, values of 50%PWT of ipsilateral hindpaws in SNL group were significantly lower than those of the blank control group and shame operation group （P<0.01); the values of 50%PWT of the ipsilateral hindpaws in SNL+VU0155041 group were gradually higher than those of SNL+saline group from the forth day after injection (P<0.01); and the results of Agilent gene chip showed that Rab5 in SNL+saline group was higher than that of control group, while control group has no difference with SNL+VU0155041 group. The expression of mGluR4 in SNL+saline group was significantly lower than that of control group and SNL+VU0155041 group （P<0.05）, but the expression of Rab5A and Rab5C were significantly higher than those of control group and SNL+VU0155041 group （P<0.05), and the differences of Rab5B expression among three groups were not statistically significant （P>0.05). Conclusion The activation of mGluR4 can affect neuropathic pain by regulating neurotransmitter release of synaptic vesicles through Rab5A and Ran5C.

Key words: metabotropic glutamate receptor 4, Rab5, neuropathic pain