Reduction of Tumor Necrosis Factor (TNF) in the Hippocampus Alleviates Neuropathic Pain Perception

This investigation showed that the perception of neuropathic pain can be alleviated by attenuating hippocampal TNF levels using TNF small inhibitory RNA complexed to gold nanorods (GNR-TNF siRNA; TNF nanoplexes) for delivery and protection of siRNA. Sprague-Dawley rats received chronic constriction injury (CCI) to the right sciatic nerve. Withdrawal latencies to a noxious thermal stimulus (hyperalgesia) and withdrawal to innocuous forces (allodynia) were recorded every other day for 10 days and compared to baseline values and to sham-operated rats. Four days after CCI/sham, subgroups of rats received microinjection of either GNR-TNF siRNA or GNR-scrambled siRNA (control nanoplex) into the contralateral (left) hippocampus. Thermal hyperalgesia and mechanical allodynia were alleviated in CCI rats receiving hippocampal TNF nanoplex microinjection, which decreased bioactive TNF levels. These data indicate that hippocampal TNF concentration is integral to the modulation of pain perception.