Chronic 疼痛 and the powerhouse of the cell: UNE receives $2 million to study molecular basis of chronic 疼痛

每年有超过5000万美国人受到慢性疼痛的影响, 造成了巨大的个人和社会成本.

More than half of chronic 疼痛 patients report inadequate 疼痛 relief from medical treatment. 更糟糕的是，处方阿片类药物, 而一些最有效的止痛药物, 会有严重的副作用吗, including the potential for addiction — fueling the opioid crisis and contributing to the dramatic increase in overdose deaths over the past 10 years.

One of the major challenges in effectively treating chronic 疼痛 is that there are changes in the molecular mechanisms that give rise to 疼痛 as it transitions from acute (immediate) to chronic 疼痛. As a result, many treatments that are effective for acute 疼痛 don’t work well for chronic 疼痛.

一个五年, $2 million R01 grant to the University of New England from the National Institute of Neurological Disorders and Stroke, 美国国立卫生研究院(NIH)的一个部门, 旨在确定这些途径并寻求开发新途径的方法, 非成瘾性治疗方案.

“Primary 疼痛-sensing neurons send information about potential injuries from the body into the spinal cord, 然后在哪里传递到大脑. The molecules that create those signals in the 疼痛-sensing neurons can change in response to injury, so you can have different molecules responsible for chronic 疼痛 than for acute 疼痛,德里克·莫里弗说, Ph.D.，香港大学教授 正规澳门赌场网络生物医学科学 也是这个项目的首席研究员. 结果是, 你可以服用非甾体抗炎药, 比如布洛芬, 这对急性机器很有效, 但慢性机制是另一回事. 我们需要一套完全不同的工具来治疗慢性疼痛, but we can't develop those tools until we identify the molecular machinery that's driving chronic 疼痛.”

Molliver and his team have identified unique features of mitochondria — the structures that produce energy for cells to function — as a potential pathway to chronic 疼痛.

Because 疼痛-sensing neurons require vast amounts of energy to transmit 疼痛 signals, Molliver解释, he theorizes that chemical signals emitted by the mitochondria can adjust how easily a 疼痛-sensing neuron is activated. 更多的激活意味着更多的疼痛. 通过使用药物来调节线粒体的工作强度, the team have been able to reduce the 疼痛 signals sent by the sensory neurons.

“Everything that a neuron does is regulated in some way by the balance between its need for energy and its need to create the raw materials that allow it to do its work. The mitochondria are at the center of that balance,” Molliver解释.

研究ers in the Molliver Lab will investigate the signaling mechanisms that allow mitochondria — the “powerhouses of the cell”— to alter the function of 疼痛-sensing neurons in mice.

这项研究试图理解其中的原因, 受伤后, 有些病人恢复得很好，为什么有些人会发展成慢性的, 通常终身, 疼痛. Experiments will explore new approaches to suppressing 疼痛 by adjusting the function of the mitochondria in rodent and human cells — including the use of a cell line created from human sensory neurons to explore these mechanisms in human cells — with the goal of creating new therapies that can target the mechanisms that give rise to chronic 疼痛.

“We are very excited to be developing the potential utility of this cell line for 疼痛 research,”莫里弗说. “这是重要的一步, because while rodent neurons are similar to human neurons in many ways, it is necessary to confirm that the key signaling pathways that we identify are the same in rodents and humans in order to develop effective new treatments for patients.

“This approach will also allow us to use fewer animals in our research,” he added.

从那里, the researchers will explore molecular methods for anti-nociceptive, 或疼痛-blocking, therapies by suppressing the action of the mitochondria in animal cells with the goal of creating new therapies that can pinpoint the mechanisms of chronic 疼痛.

“现在, there’s no way to look at two patients with the same injury and tell which one will recover and which one will develop a long-lasting chronic 疼痛 condition,”莫里弗说. “If we can identify the cell signaling pathways that change during the transition from acute to chronic 疼痛, then we can begin to develop non-addictive drugs that directly target the unique features that produce chronic 疼痛.”

Molliver added that this research may open doors to groundbreaking treatments for ailments other than chronic 疼痛.

“Another exciting aspect of this project is that mitochondria are evolutionarily very old and present in every cell in the body,他说. “展望未来, there is a possibility that whatever we learn about mitochondrial control of cellular function in 疼痛-sensing neurons may improve our understanding of other, apparently unrelated disorders in which mitochondria are known to play a role, 从神经退行性疾病到心血管疾病.”