Arthritis Pain Found to Stimulate Emotions

MANCHESTER, England, March 28 -- PET scans suggest that arthritis pain and fear go hand in hand, investigators here said.

When arthritis patients feel knee pain, regions of the brain involved in processing of fear, emotions, and aversive conditioning -- the medial pain matrix -- light up on PET scans, reported Bhavna Kulkarni, M.R.C.P., Ph.D., of the University of Manchester here, and colleagues, in the April issue of Arthritis & Rheumatism.

"The present study, added co-author Anthony K.P. Jones, F.R.C.P. M.B.B.S., "demonstrates the importance of the medial pain system during the experience of arthritic pain and suggests that it is a likely target for both pharmacologic and nonpharmacologic interventions."

The investigators sought to determine whether experimentally induced acute pain, which is processed in both the medial and lateral pain matrices of the brain, is the same as the clinical pain felt by those with conditions such as arthritis of the knee.

"The medial pain system comprises structures including the medial thalamus and the perigenual, midcingulate, and insular cortices, and is involved in processing the affective (emotional) aspects of pain," the authors noted.

"The lateral pain system is involved in processing the sensory-discriminative (intensity, location, and duration) aspects of pain," they continued, "and comprises the lateral thalamus and its projections to the primary and secondary somatosensory cortices in addition to thalamoinsular projections from the ventromedial posterior nucleus of the thalamus."

The investigators enrolled 12 patients with osteoarthritis of the knee into a functional neuroimaging study using PET enhanced with 18F-fluorodeoxyglucose (FDG). They scanned the patients while they were having arthritic knee pain, experimentally induced knee pain created by heating the skin over the joint, and while they were pain free.

The authors used statistical parametric mapping software to see whether there might be significant differences in the neuronal uptake of FDG between the different pain states.

The patients were asked to rate pain intensity and "unpleasantness" on a scale of 0 (none) to 100 (worst). The ratings were performed starting 10 minutes before the injection of FDG, and then every 10 minutes until the end of the scan.

The investigators saw on FDG-PET that both the arthritic knee pain and the experimental pain activated the entire pain matrix, measured as a function of regional cerebral glucose metabolism.

But when they compared scans acquired during arthritic knee pain with those taken during the experimentally induced pain state, they found that the arthritic pain was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala -- areas involved in the processing of fear, emotions, and in aversive conditioning.

"It has been previously shown that activity within the medial pain system and related structures is increased during selective attention to the unpleasantness of an experimental pain stimulus," they wrote. "Therefore, the present findings are consistent with the idea that, for these patients, arthritic pain has more emotional salience than does experimental pain. This is also consistent with the trend toward higher scores for the unpleasantness of arthritic pain compared with the unpleasantness of experimental pain observed in this study, although the difference was not significant."

They noted that while both pain and mood were processed within the orbitofrontal, perigenual, and midcingulate cortices, there were no apparent changes in the mood states of patients between scans, suggesting that the changes in brain activation they saw were caused by the reaction to pain rather than to emotional factors.

Their findings suggested that studies of arthritis pain may need to take into account pain mechanisms beyond those set into motion by experimentally induced pain, they wrote, and pointed to new avenues for drug research.

"Considering the recent concerns about the long-term safety of cyclo-oxygenase inhibitors, we hope that our current findings will stimulate partnerships between academia and the pharmacological industry to develop a new class of analgesics for arthritic pain that specifically target the medial pain system," Dr. Jones said.

The authors acknowledged that in addition to the small sample size, the study may have been limited by the fact that they were comparing two different pain sources.