UA College of Medicine Researchers Discuss Chronic Pain in Scientific American Mind

<p>&quot;Persistent, unrelenting pain &ndash; chronic pain &ndash; can precipitate a host of debilitating conditions &ndash; depression, sleep disorders, poor judgment and perhaps even atrophy in the brain.&quot;</p>

TUCSON, Ariz. – Persistent, unrelenting pain – chronic pain – can precipitate a host of debilitating conditions – depression, sleep disorders, poor judgment and perhaps even atrophy in the brain.

It can result from physical trauma, diseases such as cancer and diabetes and other conditions that cause damage to nerves. Its occurrence is unpredictable – sometimes appearing after a minor injury and persisting long after the injury is healed – and its underlying causes are somewhat of an enigma.

What’s more, millions of people worldwide are believed to suffer from this perplexing condition, and currently available therapies have limited success in treating chronic pain.

Researchers with The University of Arizona’s highly acclaimed Pain Research Group in the College of Medicine Department of Pharmacology are searching for solutions to the chronic pain puzzle, hoping to find clues to better treatments. In their article, “When Pain Lingers,” published in the current edition of Scientific American Mind, Frank Porreca, PhD, professor of pharmacology and anesthesiology, and Theodore Price, PhD, assistant professor of pharmacology, explore the biological bases of chronic pain.
The authors differentiate between a pain pathway that provides a protective response to potentially damaging situations, like touching a hot stove, and one that reacts abnormally to mild stimuli, such as wind, water or fabric against an individual’s skin. They say that the latter phenomenon, known as allodynia, and “spontaneous” pain, which occurs without external stimuli, reflect pathological changes in pain pathways and represent a disease in and of itself.

Citing their own research and that of fellow neuroscientists, Drs. Porreca and Price suggest that the common denominator for chronic pain is hyperexcitable neurons along the pain pathway, from the site of the injury to the dorsal horn of the spinal cord (neuronal center that receives sensory information from the body) to the brain.

On a molecular level, specific proteins, known as sodium channels, on the membranes of neurons transmit electrical messages and help to determine the sensitivity or excitability of a neuron. In chronic pain states, these channels are found to cluster at the endings of the neurons near the skin and along the nerve, likely making the neurons more responsive to input.

Other research points to the neurons in the dorsal horn of the spinal cord as major players in chronic pain. Recent data suggest that when pain becomes chronic, these spinal cord neurons undergo long-term potentiation (LTP), a long-lasting improvement in communication between two neurons. LTP also underlies the formation of certain types of memories in the brain. In the same way that it represents a molecular mechanism of memory storage in brain cells, LTP may underlie the ability of spinal cord neurons to sustain a state of chronic pain.

Pain signals and the experience of pain also are influenced by a nerve circuit that begins in the brain and leads down to the spinal cord. When this circuit is activated, it mediates pain suppression. When an acute injury occurs, a set of cells in the brain stem sends out a signal that amplifies incoming pain signals, setting the stage for chronic pain.

Parts of the brain that govern emotion – the pre-frontal cortex and amygdala and the anterior cingulate cortex – also can become hyperactive in chronic pain conditions, increasing the intensity of pain and augmenting the aversive qualities of the experience. In this case, the authors point out, emotional and cognitive assessments control pain behavior and can lead to cognitive deficiencies, such as a decreased ability to assess risk and reward. Brain changes occurring with long-lasting pain also may underlie difficulties in concentrating and muddled thinking. One study reports a shrinking of the pre-frontal cortex in patients with long-lasting back pain, roughly equivalent to that seen in 10 to 20 years of aging.

Drs. Porreca and Price conclude with a discussion of potential strategies for dealing with chronic pain, including advanced diagnostic techniques; identification of biomarkers that could lead to early detection and treatment, as well as to therapies tailored to the individual; behavioral techniques, such as physical exercise and puzzle-solving, that may help address the cognitive decline that can accompany chronic pain; and new analgesics and anti-amplification therapies that not only may ease suffering, but prevent structural brain changes and possibly neurodegeneration, actually reversing the disease process.

The University of Arizona Pain Research Group is a highly collaborative and multi-disciplinary team consisting primarily of faculty from the Department of Pharmacology. The group utilizes the most advanced approaches and core facilities offered at the UA College of Medicine, including genomics, proteomics, advanced microscopy and small-animal imaging for cutting-edge research to address significant health-related questions. Chronic pain affects the lives of some 30 million people in the United States, including many of our fellow Arizonans. The Pain Research Group has strong intramural collaborative interactions with members of the Arizona Cancer Center, the UA Sarver Heart Center, UA Departments of Pathology, Neurology, Molecular and Cellular Biology, and Chemistry as well as many extramural collaborations. Federal and non-federal funding currently supports the research activities of 18 post-doctoral fellows, 20 graduate students and 12 undergraduate students. The faculty members participate in all aspects of academic life including teaching medical students and graduate students in the Graduate Program in Medical Pharmacology, as well as intramural service to the College and the University, and in a broad array of extramural service and community activities.