Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

AIDS patients frequently suffer from neurological disease as a result of infection by the human immunodeficiency virus (HIV). One in two patients suffers from chronic pain. Unlike many forms of serious pain which respond to morphine and other drugs, HIV associated "neuropathic" pain fails to respond to currently available drugs. We know that HIV promotes the production of toxic proteins which damage sensory pain nerves whilst causing them to generate pain impulses which constantly enter the spinal cord and brain. To find out how this happens, we will first explore the actions of a toxic viral protein called Vpr. We will use electrical recordings of sensory nerve activity in the presence and absence of the protein to determine which ion channels are affected. Ion channels are protein pores in nerve cell membranes which control their electrical activity and enable them to generate nerve impulses. We will then use drugs such as "K+ channel activators" to correct the effects of Vpr on sensory neuron activity. Mice which have been genetically engineered to make the viral protein Vpr (in the absence of HIV infection) display pain-related behaviors. We will see if the drugs that correct Vpr induced changes in sensory nerve activity can also stop pain in these animals. If so this will lead to the development of urgently needed treatments for pain in AIDS patients