MANCHESTER, United Kingdom—Knee osteoarthritis (OA) patients process arthritic pain and experimental pain in slightly different ways, and the difference might lead to a new class of analgesics for arthritis, according to lead author Bhavna Kulkarni, MRCP, PhD, with the Human Pain Research Group at the University of Manchester Rheumatic Diseases Centre, in the United Kingdom.¹ Reporting in the April issue of Arthritis & Rheumatism, Dr. Kulkarni and colleagues write that arthritic pain was associated with substantially more activation of brain areas associated with emotion.

"Both [arthritic and experimental] pain conditions activated the pain matrix, but arthritic pain was associated with increased activity in the cingulate cortex, the thalamus, and the amygdala; these areas are involved in the processing of fear, emotions, and in aversive conditioning," Dr. Kulkarni writes.

Different pains "felt" in different brain areas

The researchers used ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain in 12 patients with knee OA during three different knee pain states: arthritic, experimentally induced, and pain-free. Their goal was to determine whether OA patients have different pain-processing patterns for arthritic pain versus brief, acute, experimental pain.

This study was conducted by way of previous experimental work showing that pain is processed within a network of brain structures known as the ‘pain matrix.' The two components of this matrix are the lateral pain system, which processes sensory-discriminative aspects of pain, such as intensity, location and duration, and the medial pain system, which processes the affective (emotional) aspects of pain.

The lateral pain system involves areas in the lateral thalamus and its projections to the primary and secondary somatosensory cortices, as well as thalamoinsular projections from the ventromedial posterior nucleus of the thalamus. The medial pain system involves areas in the medial thalamus and the perigenual, midcingulate, and insular cortices.

Medial pain system plays role in affect, aversive conditioning, motivational responses

"The results of this study show that both the medial and lateral pain systems are activated during arthritic and experimental pain, but that the medial system is more active during arthritic pain. To our knowledge, this study is the first to document the cerebral substrates of the perception of arthritic pain. It is also the first study to directly compare experimental pain with ongoing clinical pain in the same group of patients at the same level of perceived pain intensity. The finding that both experimental pain and arthritic pain activate the medial and lateral pain systems suggests that there is no unique brain network for processing arthritic pain," the researchers conclude.

The study results also suggest that the endogenous opioid system is a potential target for new analgesics aimed at arthritic pain. Compared with the lateral pain system, the medial pain system has higher concentrations of opiate receptors and the function of these receptors can be altered by endogenous opioid peptides such as enkephalins.

"The identification of brain-specific inhibitors of enkephalin breakdown raises the possibility of enhancing such endogenous responses without the gastrointestinal side effects associated with most of the currently available analgesics," Dr. Kulkarni reports.

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Reference

1. Kulkarni B, Bentley DE, Elliott R, et al. Arthritis pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum. 2007;56:1345-1354.