Souza Alessandra H, Ferreira Juliano, Cordeiro Marta do Nascimento, Vieira Luciene Bruno, De Castro Celio J, Trevisan Gabriela, Reis Helton, Souza Ivana Assis, Richardson Michael, Prado Marco A M, Prado Vânia F, Gomez Marcus Vinicius
Departamento de Farmacologia, ICB, UFMG, 31270-901 Belo Horizonte, MG, Brazil Departamento de Quimica UFSM, 97105-900 Santa Maria, RS, Brazil Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil Departamento de Bioquimica e Imunologia, ICB, UFMG, 31270-901 Belo Horizonte, MG, Brazil Nucleo Pós Graduação, Santa Casa de Belo Horizonte, Brazil Robarts Research Institute, University of Western Ontario, London, Ontario, Canada Laboratório de Neurociência, Faculdade de Medicina, UFMG, 30130-100, Brazil.
Pain. 2008 Nov 15;140(1):115-126. doi: 10.1016/j.pain.2008.07.014. Epub 2008 Sep 6.
Calcium influx through neuronal voltage-sensitive calcium channels (VSCC S) mediates nociceptive information in the spinal dorsal horn. In fact, spinally administered VSCC S blockers, such as omega-conotoxin MVIIA, have analgesic effect apart of their low therapeutic index and many side effects. Here we study the analgesic potential of Ph alpha 1beta, a calcium channel blocker, in rodent models of acute and persistent pain. Spinally administered Ph alpha 1beta showed higher efficacy and long-lasting analgesia in a thermal model of pain, when compared with omega-conotoxin MVIIA. Moreover, Ph alpha 1beta was more effective and potent than omega-conotoxin MVIIA not only to prevent, but especially to reverse, previously installed persistent chemical and neuropathic pain. Furthermore, the analgesic action of both toxins are related with the inhibition of Ca2+-evoked release of pro-nociceptive neurotransmitter, glutamate, from rat spinal cord synaptosomes and decrease of glutamate overflow in cerebrospinal fluid. When side effects were assessed, we found that Ph alpha 1beta had a therapeutic index wider than omega- conotoxin MVIIA. Finally, recombinant Ph alpha 1beta expressed in Escherichia coli showed marked analgesic activity similar to the native toxin. Taken together, the present study demonstrates that native and recombinant Ph alpha 1beta have analgesic effects in rodent models of pain, suggesting that this toxin may have potential to be used as a drug in the control of persistent pathological pain.
通过神经元电压敏感性钙通道（VSCC S）的钙内流介导脊髓背角的伤害性信息。事实上，脊髓给予的VSCC S阻滞剂，如ω-芋螺毒素MVIIA，除了治疗指数低和有许多副作用外，还具有镇痛作用。在这里，我们研究了钙通道阻滞剂Ph alpha 1beta在急性和持续性疼痛的啮齿动物模型中的镇痛潜力。与ω-芋螺毒素MVIIA相比，脊髓给予Ph alpha 1beta在热痛模型中显示出更高的疗效和持久的镇痛作用。此外，Ph alpha 1beta不仅在预防方面，而且特别是在逆转先前已形成的持续性化学性和神经性疼痛方面比ω-芋螺毒素MVIIA更有效且作用更强。此外，两种毒素的镇痛作用都与抑制Ca2 +诱导的来自大鼠脊髓突触体的促伤害性神经递质谷氨酸的释放以及脑脊液中谷氨酸溢出的减少有关。当评估副作用时，我们发现Ph alpha 1beta的治疗指数比ω-芋螺毒素MVIIA更宽。最后，在大肠杆菌中表达的重组Ph alpha 1beta显示出与天然毒素相似的显著镇痛活性。综上所述，本研究表明天然和重组的Ph alpha 1beta在啮齿动物疼痛模型中具有镇痛作用，表明这种毒素可能有潜力用作控制持续性病理性疼痛的药物。
