Grant: Project Grant

Neuropathic pain is a chronic condition that afflicts 10% of the population and represents a major public health burden, impacting quality of life and social resources. Neuropathic pain may result from injury, viral infection, multiple sclerosis, diabetes or chemotherapy. Abnormal processes that take place at the periphery and in the brain are responsible for this unresolved form of pain. Clinical symptoms include extreme sensitivity to touch and cold temperature as well as recurrent periods of spontaneous sharp, jabbing, throbbing or burning pain. Although significant advances have been made in our understanding of the mechanisms of intractable neuropathic pain, treatments still rely on classical analgesics, including morphine or anti-epileptic drugs that have limited efficacy and numerous side effects. Our lab has discovered a novel biological mechanism of spontaneous neuropathic pain. This process involves a molecule (ALKAL2) from the nervous system, implicated in cancer. Strikingly, we showed that blocking the receptor molecule with anti-cancer drugs are able to attenuate neuropathic pain in mice. Our project will determine the biological processes by which ALKAL2 orchestrates the establishment of recurrent neuropathic pain after injury. We will develop and test ALKAL2 inhibitors that could mitigate neuropathic pain and thus relieve the suffering of millions of people worldwide.