Abstract
Chronic pain coincides with myriad functional alterations throughout the brain and spinal cord. While spinal cord mechanisms of chronic pain have been extensively characterized in animal models and in vitro, to date, research in patients with chronic pain has focused only very minimally on the spinal cord. Previously, spinal cord functional magnetic resonance imaging (fMRI) identified regional alterations in spinal cord activity in patients (who were not taking opioids) with fibromyalgia, a chronic pain condition. Here, in patients with fibromyalgia who take opioids (N = 15), we compared spinal cord resting-state fMRI data vs. patients with fibromyalgia not taking opioids (N = 15) and healthy controls (N = 14). We hypothesized that the opioid (vs. non-opioid) patient group would show greater regional alterations in spinal cord activity (i.e., the amplitude of low frequency fluctuations or ALFF, a measure of regional spinal cord activity). However, we found that regional spinal cord activity in the opioid group was more similar to healthy controls, while regional spinal cord activity in the non-opioid group showed more pronounced differences (i.e., ventral increases and dorsal decreases in regional ALFF) vs. healthy controls. Across patient groups, self-reported fatigue correlated with regional differences in spinal cord activity. Additionally, spinal cord functional connectivity and graph metrics did not differ among groups. Our findings suggest that, contrary to our main hypothesis, patients with fibromyalgia who take opioids do not have greater alterations in regional spinal cord activity. Thus, regional spinal cord activity may be less imbalanced in patients taking opioids compared to patients not taking opioids.
Highlights
Chronic pain states and opioid medication use both can alter the central nervous system (CNS) via effects on neurophysiologic mechanisms within the brain and spinal cord
We focused our analysis on the cervical spinal cord based on technological availability
We identified between group differences in graph metrics using a repeated measures general linear model across link densities for each of three group comparisons [1] healthy controls vs. non-opioid patients, [2] healthy controls vs. opioid patients, and [3] non-opioid patients vs. opioid patients
Summary
Chronic pain states and opioid medication use both can alter the central nervous system (CNS) via effects on neurophysiologic mechanisms within the brain and spinal cord. Measurement of spinal cord activity in human chronic pain patients is essential for our understanding of chronic pain because the spinal cord represents the CNS nexus where peripheral inputs, local spinal cord circuits, as well as descending modulatory circuits from supraspinal and brainstem areas all intersect. Opioid Fibromyalgia Spinal Cord Activity from both chronic pain and opioid use. Opioid analgesics exert their pain-relieving effects by acting both locally within the spinal cord dorsal horn and in the brain, which in turn, activates descending inhibition of pain via brainstem to spinal cord projections [1]. Investigating the CNS, and the spinal cord, in patients taking opioids may provide insight to how long-term opioid use influences neurophysiology, and thereby provide an additional marker to identify concerns and/or assess appropriateness of opioid use
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