Role of mGluR5 in laterocapcular division of central nucleus of amygdala in fentanyl-induced hyperalgesia in rats

Abstract

To investigate the role of metabotropic glutamate receptor 5 (mGluR5) in laterocapcular division of the central nucleus of amygdala (CeLC) in fentanyl-induced hyperalgesia in rats. Methods: A total of 12 Sprague-Dawley male rats (60-100 g) were randomly divided into a normal group 1 (n=6) and an opioid-induced hyperalgesia (OIH) group 1 (n=6). The OIH group 1 was injected with fentanyl through the lower neck skin to build OIH model, and the normal group 1 was given the same volume of saline. After 6.5 h, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested to verify the success of the induction of OIH. Then rats were sacrificed and the right CeLC tissue were taken for detection of the mGluR5 by Western blotting. Forty SD male rats were randomly divided into 4 groups (n=10 each): an OIH+DMSO, an OIH+MTEP (3.0 μg), an OIH+MTEP (7.5 μg) and an OIH+MTEP (15.0 μg) group. MTEP was a selective antagonist of mGluR5. Catheterization in the right CeLC was first performed. After one-week recovery, OIH was induced. Then 0.5 μL DMSO, MTEP 3.0 μg, MTEP 7.5 μg and MTEP 15.0 μg were administrated through the CeLC catheter accordingly. PWMT and PWTL were tested at pre-OIH, 6 h after OIH and post-drug. Then the expression levels of mGluR5 of CeLC tissue were analyzed by Western blotting. Another 8 SD male rats were randomly divided into a normal group 2 and an OIH group 2 (n=4 each). The rats were induced OIH by injecting of fentanyl while rats in the normal group 2 were injected with same volume of saline. The miniature excitatory postsynaptic currents (mEPSCs) of the 2 groups' neurons in the right CeLC region were recorded by whole cell voltage-clamp before and after the administration of MTEP in brain slice. Results: Compared with the normal group 1, the PWTL and PWMT were significantly decreased and the expression of mGluR5 was apparently increased in the OIH group 1 (P<0.05). The PWMT and PWTL were significantly decreased in each group and indicated success of OIH model (P<0.05). The expression of mGluR5 in the CeLC was increased. MTEP reversed these changes in a dose-dependent way (P<0.05). Compared with the normal group 2, the amplitude and frequency of mEPSCs in the OIH group 2 were significantly increased (P<0.05) and they were reversed by MTEP (P<0.05). Conclusion: mGluR5 in the CeLC may be involved in the maintenance of OIH. Inhibition of the activity of mGluR5 in the CeLC may alleviate the symptoms of fentanyl-induced hyperalgesia.