Activation of the Mammalian Target of Rapamycin in the Rostral Ventromedial Medulla Contributes to the Maintenance of Nerve Injury-Induced Neuropathic Pain in Rat

Figure 6

Intra-RVM microinjection of the mTOR inhibitor rapamycin (250 μM) partially reversed established mechanical allodynia (maintenance stage) but showed no effect on the induction stage of SNI-induced neuropathic pain in rats. (a) Representative Nissl-stained section showing injection sites within the RVM (4V: 4th ventricle; py: pyramidal tract). Scale bar = 500 μm. (b) Camera lucida drawings showing the cannula tip placements in rats injected with rapamycin (black circles, ) or vehicle (white circles, ) in the RVM. The numbers correspond to the distance in millimeters (mm) posterior to bregma in the brain. (c) Experimental schedule. The behavioral tests, cannula implantation, microinjection, and SNI surgery were performed as indicated in the schedule. (d) Intra-RVM microinjection of rapamycin (250 μM) before SNI (Pre-SNI) and 1 day after SNI (SNI-D1) could not alleviate mechanical allodynia 30 min after the SNI-D1 injection compared to vehicle injection ( rats/group). (e) Microinjection of rapamycin (250 μM) into the RVM 30 min before the behavioral test significantly reduced mechanical allodynia at 7 days after SNI (SNI-D7) compared to vehicle injection (, rats/group).

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