Pain chronification impacts whole-brain functional connectivity in women with hip osteoarthritis during pain stimulation

Abstract Objective Previous neuroimaging studies have shown that patients with chronic pain display altered functional connectivity across distributed brain areas involved in the processing of nociceptive stimuli. The aim of the present study was to investigate how pain chronification modulates whole-brain functional connectivity during evoked clinical and tonic pain. Methods Patients with osteoarthritis of the hip (n = 87) were classified into 3 stages of pain chronification (Grades I–III, Mainz Pain Staging System). Electroencephalograms were recorded during 3 conditions: baseline, evoked clinical hip pain, and tonic cold pain (cold pressor test). The effects of both factors (recording condition and pain chronification stage) on the phase-lag index, as a measure of neuronal connectivity, were examined for different frequency bands. Results In women, we found increasing functional connectivity in the low-frequency range (delta, 0.5–4 Hz) across pain chronification stages during evoked clinical hip pain and tonic cold pain stimulation. In men, elevated functional connectivity in the delta frequency range was observed in only the tonic cold pain condition. Conclusions Across pain chronification stages, we found that widespread cortical networks increase their synchronization of delta oscillations in response to clinical and experimental nociceptive stimuli. In view of previous studies relating delta oscillations to salience detection and other basic motivational processes, our results hint at these mechanisms playing an important role in pain chronification, mainly in women.