@article{discovery1466016,
          volume = {297},
           month = {April},
         journal = {Neuroscience},
           title = {Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats.},
            year = {2015},
            note = {{\copyright} 2015 The Authors. Published by Elsevier Ltd. on behalf
of IBRO. This is an open access article under the CC BY
license (http://creativecommons.org/licenses/by/4.0/).},
           pages = {47 -- 57},
          author = {Patel, R and Rutten, K and Valdor, M and Schiene, K and Wigge, S and Schunk, S and Damann, N and Christoph, T and Dickenson, AH},
        abstract = {Prialt, a synthetic version of Cav2.2 antagonist {\ensuremath{\omega}}-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Cav2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Cav2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury.},
             url = {http://dx.doi.org/10.1016/j.neuroscience.2015.03.057},
        keywords = {Ca(v)2.2, N-type calcium channel, dorsal horn, dorsal root ganglia, electrophysiology, spinal nerve ligation}
}