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Up-regulation of Cavbeta3 subunit in primary sensory neurons increases voltage-activated Ca2+ channel activity and nociceptive input in neuropathic pain

High voltage-activated calcium channels (HVACCs) are essential for synaptic and nociceptive transmission. Although blocking HVACCs can effectively reduce pain, this treatment strategy is associated with intolerable adverse effects. Neuronal HVACCs are typically composed of alpha(1), beta (Cavbeta), and alpha(2)delta subunits. The Cavbeta subunit plays a crucial role in the membrane expression and gating properties of the pore-forming alpha(1) subunit. However, little is known about how nerve injury affects the expression and function of Cavbeta subunits in primary sensory neurons. In this study, we found that Cavbeta(3) and Cavbeta(4) are the most prominent subtypes expressed in the rat dorsal root ganglion (DRG) and dorsal spinal cord. Spinal nerve ligation (SNL) in rats significantly increased mRNA and protein levels of the Cavbeta(3), but not Cavbeta(4), subunit in the DRG. SNL also significantly increased HVACC currents in small DRG neurons and monosynaptic excitatory postsynaptic currents of spinal dorsal horn neurons evoked from the dorsal root. Intrathecal injection of Cavbeta(3)-specific siRNA significantly reduced HVACC currents in small DRG neurons and the amplitude of monosynaptic excitatory postsynaptic currents of dorsal horn neurons in SNL rats. Furthermore, intrathecal treatment with Cavbeta(3)-specific siRNA normalized mechanical hyperalgesia and tactile allodynia caused by SNL but had no significant effect on the normal nociceptive threshold. Our findings provide novel evidence that increased expression of the Cavbeta(3) subunit augments HVACC activity in primary sensory neurons and nociceptive input to dorsal horn neurons in neuropathic pain. Targeting the Cavbeta(3) subunit at the spinal level represents an effective strategy for treating neuropathic pain

Keywords : adverse effects,Affect,Anesthesiology,Animals,Base Sequence,Calcium,Calcium Channels,Down-Regulation,Ganglia,Spinal,genetics,Glutamic Acid,Hyperalgesia,injuries,Ligation,Male,metabolism,Neuralgia,Neurons,Nociception,Pain,pathology,physiology,physiopathology,Posterior Horn Cells,Protein Transport,Rats,Rats,Sprague-Dawley,Sensory Receptor Cells,Spinal Cord,Texas,transmission,Universities,Up-Regulation,, Cav?3,Subunit,Primary, personal injury claims london

Date of Publication : 2012 Feb 17

Authors : Li L;Cao XH;Chen SR;Han HD;Lopez-Berestein G;Sood AK;Pan HL;

Organisation : Department of Anesthesiology and Perioperative Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA

Journal of Publication : J Biol Chem

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22187436

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Up-regulation of Cav?3 Subunit in Primary Sensory Neurons Increases Voltage-activated Ca2+ Channel Activity and Nociceptive Input in Neuropathic Pain | Facet joint pain

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