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.
