Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord

Abstract

BackgroundFor their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model.MethodsMechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence.ResultsIntrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons.ConclusionsIntrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

Intrathecal administration of human bone marrow mesenchymal stem cells genetically modified with human proenkephalin gene decrease nociceptive pain in neuropathic rats

“…So, much research still needed to understand the homing capabilities of BMSCs. Intrathecal administration was used in this study for which had been proved a viable and effective option for gene therapy of chronic pain 24 , 25 in former studies.…”

Effects of Hericium erinaceus Mycelium Extracts on the Functional Activity of Purinoceptors and Neuropathic Pain in Mice with L5 Spinal Nerve Ligation

“…SNL-induced neuropathic pain is related to P2R activity [8]. In one study, the expression and production of spinal P2X7R increased following SNL surgery [34], while in another, the expression levels of P2X7R in the spinal cord segment were higher in the nerve surgery group than in the sham group [35,36]. Finally, P2X4 mRNA expression levels in the spinal horn increased following SNL surgery in mice [37].…”

Activation of the P2X7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats

“… 48 – 50 Previous research has suggested the presence of P2X 7 receptor in the dorsal root ganglion and spinal cord dorsal horn and its involvement in neuropathic pain mechanism in rats. 51 , 52 The studies suggested that P2X 7 receptors are involved in the modulation of neuropathic pain in relation to the following factors. (1) Purine signaling can be conducted by non-synaptic routes.…”