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.
Highlights
For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries
If the processed Aconitum plant inhibits the expression of purinergic receptor on microglia, it is possible that it may inhibit microglial activation, thereby contributing to the attenuation of neuropathic pain
Supporting this hypothesis, a previous in vitro study demonstrated that Bullatine A, a diterpenoid alkaloid of the genus Aconitum, suppressed adenosine triphosphast (ATP)-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in BV-2 microglial cells.[10]
Summary
For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Blockade of voltage-dependent sodium channels of neurons is considered the primary mechanism underlying the analgesic effects Aconitum plants.[4,5,6] spinal glial cells play a significant role in the development and maintenance of neuropathic pain in addition to the involvement of neurons.[7, 8] Interestingly, lappaconitine, one of the alkaloid components of Aconitum plant species, was shown to suppress the expression of purinergic receptor in dorsal root ganglion neurons of rats with neuropathic pain.[9] If the processed Aconitum plant inhibits the expression of purinergic receptor on microglia, it is possible that it may inhibit microglial activation, thereby contributing to the attenuation of neuropathic pain Supporting this hypothesis, a previous in vitro study demonstrated that Bullatine A, a diterpenoid alkaloid of the genus Aconitum, suppressed adenosine triphosphast (ATP)-induced P2X7R-mediated inflammatory responses in BV-2 microglial cells.[10] activation of the P2X7R expressed on resting microglia is important for microglial activation in neuropathic pain [11,12,13]
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