My interest for the past 20 years has focused on chronic pain, why it happens (to some and not others, after the same apparent trauma or procedure, or disease) and how to prevent or reverse it. The two causes of chronic pain that my work is directed towards are surgery and cancer. In rodents we have developed several different models of surgical procedures that are known to cause acute (1-3 days), prolonged (1-4 weeks) and chronic (greater than one month) pain.  “Pain” is assessed by briefly applying mechanical stimuli, such as a gently push with a nylon fiber, or gentle heating, and comparing the animal’s response to that of a naïve, unoperated animal. Surgically-induced pain can be prevented by injections of certain drugs, such as resolvins,  into the spinal fluid, but once established such pain cannot be reversed by such drugs.

In cancer pain studies we have injected chemicals, such as Endothelin-1 (ET-1) and Nerve Growth Factor (NGF), which are known to be synthesized and secreted by tumors, and then examined the responses to mechanical and thermal stimulation.

Our studies have shown that both peripheral mechanisms, e.g. in the skin, and central mechanisms, e.g. in the spinal cord and brain, contribute to the development of pain responses. When injected into the hind paw, both tumor-related compounds elevate that paw’s pain responses, but ET-1 also elevates pain in the opposite, un-injected paw whereas NGF does not. Pain sensitization by NGF involves a local synthesis of certain enzymes involved in intracellular signaling (called Protein Kinases M-zeta), in the injected paw’s skin, far away from the cell body of pain neurons which is located near the spinal cord. When injected in sequence, the two agents sensitize each other’s pain-inducing actions.

My current research involves the use of intra-tumor cannabinoids to abolish tumor-related  pain.