A new drug, developed by a team of researchers at the University of Toronto, shows promise for controlling chronic pain caused by nerve damage. The drug, called NB001, produces strong pain-killing effects in mice and in human neuronal cell lines by blocking a particular enzyme produced in the neurons of the spinal cord and front region of the brain during nerve injury.
“Acute or physiological pain is necessary for animals and humans to get through daily life. Minor pain alerts the body that something is wrong,” said Professor Min Zhuo of the Department of Physiology and Centre for the Study of Pain.
“On the other hand, increased and unmanageable nerve pain, typically described as chronic ‘shooting’ or ‘burning’ sensations, has no survival benefit and is usually caused by severe injury or diseases such as cancer or AIDS.”
Chronic pain, unlike acute pain, persists even after an injury has healed; this happens when the pain signals continue to remain active in the nervous system. Prior studies have shown, however, that chronic pain is not just a prolonged version of acute pain. Specifically, it occurs from particular changes in synapses, the junctions where neurons pass electrical or chemical signals to another cell. Most conventional painkillers seem to also attack acute pain without effectively shutting off the source of chronic pain.
In the paper, the researchers show that NB001 is effective for controlling pain because it blocks a particular enzyme called type 1 adenylate cyclase (AC1), usually produced in spinal cord and brain neurons during nerve injury.
In previous studies, Zhuo and his team showed that knocking out the AC1 gene significantly reduced or got rid of chronic pain in mice. In the current study, however, the new drug works by only blocking AC1 in particular regions of the brain and spinal cord, rather than in the whole body. The dose of NB001 required for pain-killing effects is at least 10-50 times lower than current chronic pain drugs in the market.
“The findings suggest that AC1 is critical for various forms of chronic pain, but does not contribute to acute pain. Moreover, unlike other drug targets for chronic pain, AC1 is selectively expressed in neurons and thus is less likely to cause potential side effects in non-neuronal organs such as the heart, liver, and kidney,” Zhuo said.
The research is published in the journal Science Translational Medicine.
Source: University of Toronto