Pain is a major problem for physicians and the public alike, resulting in nearly $100 billion in lost productivity and health-care costs each year, according to the nonprofit Partners Against Pain. In 2006 general pain researchers around the globe advanced understanding of what underlies acute and chronic pain, as well as ways to alleviate it.

One study identified a “master switch” for the development of neuropathic pain, a chronic form of pain quite different from the acute pain of an injury. Another found that simply anticipating pain may be worse than actually experiencing it. Researchers looking for pest controls stumbled onto an enzyme blocker that may provide relief from inflammatory pain while decreasing the risk of heart attack associated with drugs such as rofecoxib (Vioxx). Canadian scientists found that mice display empathy and become sensitive to pain while watching another mouse experience pain. And researchers found that the type of placebo and the context in which it is given may enhance the placebo effect on pain perception.

Master Switch Identified for Chronic Pain

Neuropathic pain, from injury to “peripheral” nerves outside the brain and spinal cord, is characterized by a chronic shooting or burning sensation. It responds poorly to treatment with opioid drugs, which are the strongest painkillers and include such drugs as morphine, codeine, and oxycodone (brand name Oxycontin).

In the journal Neuron, researchers at Harvard Medical School reported finding a “master switch” for the development of neuropathic pain.¹ This switch, the Runx1 gene, is expressed only in sensory nerve cells called nociceptive cells, which are involved in sensing pain. These cells translate painful stimuli into nerve signals via ion channels, special pores in the nerve cell membrane.

The researchers, led by Qiufu Ma, exposed “knockout” mice (in which the Runx1 gene was removed) to thermal, mechanical, inflammatory, and neuropathic stimuli and measured their reaction to pain by how long they either lifted or licked their paw in response.

Limiting pain: A gene called Runx1 is active in pain receptors for thermal and inflammatory pain, indicated by arrows, and neuropathic pain, indicated by the arrowheads. Mice lacking the Runx1 gene did not react to these types of pain.  (Image courtesy of Qiufu Ma)

1. Chen CL, Broom DC, Liu Y, de Nooij JC, Li Z, Cen C, Samad OA, Jessell TM, Woolf CJ, and Ma Q. Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain. Neuron 2006 49(3):365–377.

2. Berns GS, Chappelo J, Cekic M, Zink CF, Pagnoni G, and Martin-Skurski ME. Neurobiological substrates of dread. Science 2006 312(5774):754–758.

3. Schmelzer, KR, Inceoglu B, Kubala L, Kim I-H, Jinks SL, Eiserich JP, and Hammock BD. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proceedings of the National Academy of Sciences USA 2006 103(37): 13640–13645.

4. Carl T. Hall, “Social factors may deepen chronic pain,” San Francisco Chronicle, November 4, 2002.

5. Sternberg WF, Scorr L, Smith LD, Ridgway CG, and Stout M. Long-term effects of neonatal surgery on adulthood pain behavior. Pain 2005 13(3):347-353.

6. Langford DJ, Crager SE, Zarrar S, Smith SB, Sotocinal SG, Levenstadt JS, Chanda ML, Levitin DJ, and Mogil JS. Social modulation of pain as evidence for empathy in mice. Science 2006 312(5782):1967–1970.

7. Kaptchuk TJ, Stason WB, Davis RB, Legedza A, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, and Goldman RH. Sham device v. inert pill: Randomized controlled trial of two placebo treatments. British Medical Journal 2006 332(7538):391–397.

8. Kong J, Gollub RJ, Rosman IL, Webb JM, Vangel MG, Kirsch I, and Kaptchuk TJ. Brain activity associated with expectancy-enhanced placebo analgesia, as measured by functional magnetic resonance imaging. The Journal of Neuroscience 2006 26(2):381–388.