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

Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.

Distinct aberrations in cerebral pain processing differentiating patients with fibromyalgia from patients with rheumatoid arthritis

“…Specifically, we previously reported diminished dlPFC activation in the current cohort of patients with RA during 2.5-second painful joint stimulation, 43 whereas increased dlPFC activation has been observed during continuous (6 minutes) but less intense painful stimulation. 32 Speculatively, the latter may reflect a stable ongoing inhibition via opioid signalling in response to continuous but lower painful stimulation intensity. However, when enough pain intensity is reached, the dlPFC may temporarily deactivate to protect the inflamed joints and to avoid additional harm.…”

Imaging clinically relevant pain states using arterial spin labeling

“…Arterial spin labeling examinations of clinical pain have become more popular in recent years. Studies of different painful conditions including inherited erythromelalgia, 79 osteoarthritis of the hand 35,40 and knee, 18 trigeminal neuralgia and temporomandibular disorder, 29,100 fibromyalgia, 81 migraine, including pediatric migraine, 15,33,39,101 interstitial cystitis/chronic pelvic pain, 22,92 chemotherapy-induced painful neuropathy, 64 postherpetic neuralgia, 54 spondylotic myelopathy, 106 painful diabetic polyneuropathy (DPN), 78 rheumatoid arthritis, 46 Gulf War Illness, 49 and complex regional pain syndrome 80 have been reported.…”

Cerebral perfusion alterations in patients with trigeminal neuralgia as measured by pseudo-continuous arterial spin labeling

“…Several studies have found underlying brain anomalies associated with chronic pain, including alterations in brain function, structure, chemistry, and cerebral perfusion ( Simons et al, 2014 ; Kregel et al, 2015 ; Kumbhare et al, 2017 ; Jung et al, 2019 ; Lee et al, 2019 ). Recent studies have reported that patients with TN have structural and functional brain alterations ( Obermann et al, 2013 ; Henssen et al, 2019 ; Yan et al, 2019 ; Zhang et al, 2021 ).…”