AAV-mediated siRNA against TRPV1 reduces nociception in a rat model of bone cancer pain

Abstract

ABSTRACTObjective: Bone cancer pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates. Transient receptor potential vanilloid subfamily member 1 (TRPV1), a new target of the analgesics, activated by heat, protons and capsaicin and the hot component of pepper. However, little is known of the anti-nociceptive effects of TRPV1 in cancer-induced bone pain. RNA interference (RNAi) has proven to be a powerful technique to study the function of genes by producing knock-down phenotypes. The aim of this study is to investigate the potential role of TRPV1 in rat model of bone cancer pain.Methods: Bone cancer pain animal model was created by tumor cell implantation (TCI). An AAV-mediated siRNA against TRPV1 was intrathecally delivered into the rats. Animal behaviors were measured using a set of mechanical or electronic von Frey apparatus and hot plate. mRNA and protein expression were examined by using qPCR and western blot methods.Results: Mechanical threshold and paw withdrawal latency in response to thermal stimulation were significantly elevated in rats with intrathecal administration of AAV-mediated siRNA against TRPV1. Moreover, class I histone deacetylases (HDACs), which plays a critical role in the neuro-inflammation response, and TNFα in the spinal cord were also significantly suppressed upon knockdown of TRPV1 by AAV-mediated siRNA against TRPV1 in rat spinal cord.Conclusions: Knockdown of TRPV1 effectively ameliorated mechanical allodynia and thermal hyperalgesia induced by TCI. Our data demonstrated that modulate the expression of TRPV1 in the spinal cord could be a potential therapeutic approach for bone cancer pain.