One in three Americans will suffer from chronic pain at some point in their lives, resulting in an estimated $635 billion per year in medical treatment and lost productivity.
To better understand the multiple dimensions of pain, including sensory, emotional and cognitive aspects, Frank Porreca and his research group in the department of pharmacology in the University of Arizona College of Medicine have been awarded a $2.5 million, five-year R01 grant from the National Institute on Drug Abuse of the National Institutes of Health.
Dr. David Borsook, professor of anesthesiology at Harvard Medical School, is a co-investigator on the 1 R01 DA 034975-01grant.
Chronic pain is defined as any pain lasting more than 12 weeks or pain that is longer than the expected time of healing. Whereas acute pain is a normal and essential mechanism that protects us from injuries, chronic pain is very different. Chronic pain persists after injuries have resolved, does not serve any useful purpose and is a burden to patients and society.
Porreca, UA professor of pharmacology andanesthesiology, and his laboratory study the neural circuits mediating pain in the brain and the spinal cord. In a key finding, the team has demonstrated that treatments that relieve the unpleasant feeling of pain also activate reward circuits and reinforce behaviors that result in the relief of pain.
"Pain is an emotion, both a sensation and a motivation. It is the unpleasantness of pain that produces strong motivation to get rid of it and to seek relief," Porreca said.
"Pain can be thought of as analogous to other aversive states that produce motivation. For example, hunger is an aversive state, and when we are hungry we are motivated to seek relief and find food; when we are thirsty we are motivated to seek water; and when we are cold we are motivated to seek warmth. Relief of the aversive states, including pain, is rewarding. We are studying the reward circuits in the brain and their response to the relief of the aversiveness of pain," Porreca explained.
Porreca's team is evaluating the activation of brain reward circuits as a way to identify new treatments that effectively relieve pain so that new medications can be discovered. There are multiple competing emotions that create motivational drives, Porreca says, and "we have to investigate the brain mechanisms that underlie chronic pain in order to discover more effective medications."
"Pain is a complex individual experience that depends on the context in which injuries may occur. We have to determine whether it is appropriate to respond to pain or to take other, more imperative action," Porreca said. "For example, in a safe setting you respond to the pain and attend to the injury that may have caused it. However, in a situation where there is a threat to survival, responding to pain is less important."
Stress can suppress pain so that escape and survival are possible, Porreca said. For example, someone injured in an automobile accident might lack pain immediately following the incident, or an athlete might lack pain following an injury during the height of competition. Porreca explained that the mechanism for pain probably has been activated in each instance, but the brain can modulate the process that produces the pain within the context of the injury.
Conversely, in chronic pain conditions, the brain may enhance or exaggerate the experience of pain and such conditions are very difficult to treat with conventional pain medications.
"Current medications used for chronic pain are ineffective for many people and have serious side-effects," Porreca said. "The novel demonstration of pain relief as a reward provides an entirely new way to discover medicines for patients."
Porreca collaborates with a multidisciplinary team at the UA that includes Regents Professor Emeritus Victor Hruby and professor Robin Polt, both with the department of chemistry and biochemistry.
Porreca works closely with research professor of pharmacology Michael Ossipov and assistant research scientists Milena De Felice, Jennifer Xie and Edita Navratilova, along with postdoctoral fellows, graduate students and visiting research fellows.