Vanderbilt University School of Medicine in Nashville, Tenn.

Dr. Sukdeb Datta on Pain Research at Vanderbilt University School of Medicine

— -- Hi, my name is Dr. Sukdeb Datta and I have been entrusted the responsibility of restarting the Pain Fellowship Program at Vanderbilt University.

My laboratory of Neuropathic pain research looks at new treatments based on potential mechanisms of neuropathic pain (pain secondary to damage of nerves) through research funded by a grant from the Department of Veterans Affairs.

At Vanderbilt we are focused on molecular neurosurgical approach, which selectively targets nerves involved in pain transmission.

Chronic pain has historically been treated in a number of ways. Strong pain medications and surgery have been used – and are helpful in many cases - but these approaches are not effective in treating all types of pain and can have adverse effects that compromise a patient's quality of life.

A neurosurgeon, for example, may cut various nerve pathways to relieve suffering but the nervous system is not "color coded," which makes it very difficult to selectively lesion pathways. Other sensory and motor nerves can be inadvertently severed, increasing the risk of paralysis or loss of sensation.

Molecular neurosurgical techniques utilized in my laboratory specifically target the neurons transmitting chronic pain while leaving other nearby neurons intact.

This technology is based on a normal function of the neuron called receptor internalization. In this process a substance such as an antibody or a neurotransmitter binds to its receptor on the neuron's surface and both are internalized by the neuron.

My mentor and collaborator, Dr. Ronald Wiley, pioneered the technique of using saporin to aid in this process. Saporin is an enzyme not normally taken up by neurons but it can be efficiently internalized when coupled with neuropeptides to inactivate ribosomes resulting in cell death. Saporin has also been called Ribosome Inactivating Protein or R.I.P. (no pun intended)

This process, referred to as "molecular neurosurgery," is very precise as only the specific receptor type is internalized and others are left intact.

My research has also focused on working with an agent called Cholecystokin (CCK), which has an antagonist relationship to morphine.

It is well known that CCK levels are increased after nerve injury and morphine works very poorly in such cases. If CCK could be destroyed, pain relief with morphine would be more effective in cases of nerve injury.

I have used the concept of "molecular neurosurgery" by working with the saporin coupled to CCK (called CCK-saporin). This effectively kills only the CCK producing neurons leaving others intact.

Initial results have been very promising.