Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial Spin Labeling

Central nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA-related pain.

Patients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling. The imaging conditions included 1) resting state, 2) low-intensity stimulus, and 3) high-intensity stimulus. Stimuli consisted of mechanical pressure applied to metacarpophalangeal (MCP) joints with an automated cuff inflator. The low-intensity stimulus was inflation to 30 mm Hg. The high-intensity stimulus was the amount of pressure required to achieve a pain intensity rating of 40 on a 100-point scale for each RA patient, with the same amount of pressure used in the matched control.

Among RA patients, regional cerebral blood flow (rCBF) in the medial frontal cortex and dorsolateral prefrontal cortex increased during both low-pressure and high-pressure stimulation. No rCBF changes were observed in pain-free controls. Region-of-interest analyses in RA patients showed that baseline rCBF in the medial frontal cortex was negatively correlated with the pressure required for the high-intensity stimulus and positively correlated with pain induced by the low-intensity stimulus. Baseline rCBF was also marginally correlated with disease activity). Regional CBF during high pain was positively correlated with pain severity and pain interference.

In response to clinically relevant joint pain evoked by pressure applied to the MCP joint, neural processing in the medial frontal cortex increases and is directly associated with clinical pain in patients with RA.