Functional connectivity modulations during offset analgesia in chronic pain patients: an fMRI study

Patients with neuropathic pain and fibromyalgia showed reduced or absent offset analgesia (OA) response and attenuated cerebral activity in descending pain modulatory and reward systems in patients. However, neural network modifications of OA in chronic pain have not been determined. We enrolled 23 patients with various chronic pain and 17 age- and gender- matched healthy controls. All participants were given OA-related noxious thermal stimuli, including 3 repeats of offset analgesia paradigm at 46-47-46 °C and constant paradigm at 46 °C on the left volar forearm under whole-brain functional magnitude resonance imaging (fMRI). We evaluated magnitude of OA, examined OA modulated functional connectivity using psychophysiological interaction analysis and resting-state functional connectivity analysis and explored their behavioral correlations in patients compared with controls.Compared to controls, chronic pain patients showed smaller magnitude of OA (P = 0.047). OA modulated connectivity decreased between posterior cingulate cortex (PCC) and right medial prefrontal cortex (MPFC) in proportion to current chronic pain (P = 0.018); decreased between right pallidum and right thalamus, and increased between right caudate nucleus and left primary somatosensory cortex (P _FDR < 0.05).The impaired PCC-MPFC connectivity might play an important role in dysfunction of OA and contribute to pain chronification.