Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Cell Mol Neurobiol. 2013 Jan;33(1):59-67. doi: 10.1007/s10571-012-9871-x. Epub 2012 Aug 7.
Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund's adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca(2+) influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca(2+) influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca(2+) channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.
电压门控钙通道（VSCCs）是细胞兴奋性的基础，参与产生和维持神经性和炎性疼痛的机制。我们在大鼠中评估了两种 VSCC 阻断剂ω-芋螺毒素 MVIIA 和 Phα1β 在完全弗氏佐剂（CFA）和慢性缩窄性损伤（CCI）分别诱导的炎性和神经性疼痛模型中的作用。我们还评估了毒素对暴露于两种疼痛模型的大鼠背根神经节（DRG）神经元中辣椒素诱导的 Ca(2+)内流的影响。单次鞘内注射 Phα1β 可逆转抑制 CFA 和 CCI 诱导的机械性痛觉过敏，作用时间长于单次注射 ω-芋螺毒素 MVIIA。Phα1β 和 MVIIA 也抑制了 DRG 神经元中辣椒素诱导的 Ca(2+)内流。Phα1β 对 CFA 模型中 DRG 神经元中辣椒素诱导的钙瞬变的抑制作用大于 CCI 模型，而 ω-芋螺毒素 MVIIA 的抑制作用在 CCI 模型中更大。慢性炎性和神经性疼痛的治疗仍然是临床医生面临的主要挑战。Phα1β 是一种对 N 型 Ca(2+)通道具有选择性的 VSCC 可逆抑制剂，具有作为治疗炎性和神经性疼痛的新型治疗剂的潜力。需要进行临床研究以确定 Phα1β 在慢性疼痛治疗中的作用。
