Real-time study provides insight into human pain process

LONDON Pain is one of those things we each experience differently. Now, by monitoring chemical activity in the brains of human volunteers subjected to sustained pain, researchers are closer to unravelling the mysteries of the body's natural painkiller system and why we each feel pain differently.Jon-Kar Zubieta and colleagues from the Department of Psychiatry, University of Michigan, show in 13 July Science, that a wide range of regions in the brain are active when the body responds to pain. Further, mu-opioid receptors — which attenuate the spread of pain messages in the brain when naturally occurring (endogenous) opioids bind to them — play a central role in an individual's experience of pain.The researchers argue that their findings may lead to a greater understanding of chronic pain and its treatment, something that will become increasingly important as the population ages and more people suffer from arthritis and other chronically painful conditions. At the same time, knowledge of what causes people to experience pain differently may help clinicians to tailor treatment or learn why certain chronic pain conditions such as a prolonged jaw pain condition called temporo-mandibular joint disorder (TMJ) and fibromyalgia are more common in women than men.Pain is a complex experience that can be thought of as comprising three elements: sensory discriminative; motivational-affective and cognitive-evaluative. The sensory discriminative element provides information about the location and intensity of pain whilst the motivational-affective component determines the conditioned response to pain. Then, using aspects of experience, the cognitive-evaluative element interprets signals and determines whether to block, modulate or enhance the perception of pain.Understanding exactly how the experience of pain is underpinned by activity in the brain is crucial to pain research. The hypothesis that Zubieta and his colleagues explored was that the endogenous opioid system, in particular the mu-opioid system, would be active in particular parts of the brain during sustained pain. Their findings confirmed and expanded this hypothesis."One of the nice things about our findings was that areas of the brain implicated with the opioid response from previous studies showed activity whilst the people were experiencing pain. The most surprising aspect, however, was the number of regions of the brain that were activated, which shows neuroreceptors modulate their response in a wide range of regions," says Zubieta.The study was the first to examine in real time how different people feel pain in the brain. Twenty people received two 20-minute injections into their jaw muscles: one containing highly concentrated salt water, which mimicked (TMJ), the other a placebo solution that caused no pain. The subjects were given the injections in a randomised, double-blind manner and the researchers ensured the intensity of pain from the salt water injection was the same for everyone.During the injection, positron emission tomography (PET) scans were taken of their brain and the activity of the mu opioid system was studied by administering [11C] carfentaril, a selective mu opioid receptor radiotracer. Subjects were asked to rate how much pain they were feeling every 15 seconds using a computerised system and they also completed a pain questionnaire about their experience at the end of the experiment.Zubieta et al. found that the pain activated mu opioid receptors in areas of the brain that are associated with the body's attempt to minimise the pain experience. They found receptor activation in the amygdala, the thalamus, the hypothalamus, the frontal cortex and the nucleus accumbens — with as much as a 12% change in mu opioid receptor availability in the prefrontal cortex. This activation of the mu opioid system was associated with a reduction in the amount of pain and pain-related emotions the volunteers said they felt.They also found a variation in the activation response within individuals, despite the fact that participants had experienced a similar pain intensity. This appeared to correlate with the individual's sensory and affective responses to the pain experience; those who had experienced the greatest change in the mu opioid system between the salt water and placebo injection tended to report the least pain."This may help explain why some people are more sensitive, or less sensitive, than others when it comes to painful sensations," says Zubieta, "We show that people vary both in the number of receptors that they have for these anti-pain chemicals, and in their ability to release the chemicals themselves. Such variability in the pain-response system may help explain why some people react to pain and pain medications differently."

Real-time study provides insight into human pain process

Observation of the brain's biochemical response to chronic pain is enabling the natural painkilling mechanisms of the body to be understood in greater detail.

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