Since then, Julius and others have characterized several TRP channels and their interconnected roles in sensory perception. HHMI investigator David Clapham, an ion channel expert at Children’s Hospital Boston and Harvard Medical School, also studies the channels, looking at their roles in a variety of sensations. He characterized a member of the human vanilloid TRP subfamily, TRPV3, found in the skin and other major organs, and showed its involvement in controlling some aspects of temperature sensitivity. His lab also identified common plant compounds used as spices and insecticides that activate TRPV3, TRPV1, TRPA1, and other TRP channels, leading to irritations and allergies.

The Role of TRP Ion Channels in Temperature Sensation
Wild type mice (TRPM8 +/+) will avoid cold surfaces. In contrast, mice lacking TRPM8 menthol receptors (TRPM8 -/-) cannot sense cold surfaces.

Receptors to Dull Pain

A major new direction in pain research began with the discovery of the family of Mas-related gene (Mrg) receptors by HHMI investigator David Anderson and his colleagues, including Xinzhong Dong, at the California Institute of Technology. Mrg receptors are found exclusively in sensory neurons. Dong, now an HHMI early career scientist at Johns Hopkins School of Medicine, has shown that while certain Mrg receptors function in itch sensation, one appears to function like the body’s naturally occurring opioid receptors, which help to dull pain. Dong is testing compounds that target this Mrg receptor, looking for ways to avoid narcotic and other side effects from opiates, which would benefit people with chronic pain.

The initial discovery that abnormal central sensitization can lead to pain hypersensitivity came from Clifford Woolf at Children’s Hospital Boston and Harvard Medical School. Woolf is now generating hypersensitive and normal human pain neurons in his laboratory from fibroblasts using stem cell techniques to characterize their differences and, perhaps, find ways to regulate their firing without harming other necessary physiological functions. He is also looking at ways to deliver pain relievers directly to hyperactive nociceptors while leaving normal ones untouched.

		Boosting the Body’s Natural Painkilling Power An HHMI early career scientist may have found a way to boost our innate painkilling power. Read More

Undoubtedly, other molecules of normal and pathological pain signaling await discovery, thereby offering additional possibilities for improving pain treatment. “I tell my medical students,” says Woolf, “that pain will be treated completely differently 10 years from now.” Physicians may one day treat pain based on both the source of pain within the patient’s nervous system and the individual’s genetic predisposition for responding to a specific therapy. Perhaps the day isn’t too far off when a physician will ask where it hurts and nearly all patients will respond, nowhere.

Video: Republished by permission from Macmillan Publishers Ltd: Nature (448, 204-208), copyright 2007.

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