Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain

Abstract

Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow-5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain.

Suppressed prefrontal cortex oscillations associate with clinical pain in fibrodysplasia ossificans progressiva

“…Using resting-state functional magnetic resonance imaging (fMRI), highly similar frequency-dependent changes have been reported in multiple chronic pain conditions. In trigeminal neuralgia [ 52 ], postherpetic neuralgia [ 12 ], and chronic back pain [ 28 , 51 ] populations, a loss of slow-5 power was not only noted in prefrontal cortex [ 52 ] but also in subcortical regions such as the nucleus accumbens, which share projections with sub-regions of the frontal cortex areas amongst other (meso-)limbic structures. Thus, in general, the suppression of the frontal cortex (potentially along the frontostriatal pathway) low-frequency oscillation in the slow-5 sub-band may represent a maladaptive cortical process that is derived from persistent pain or mechanisms that sustain a pain state.…”

Understanding Cluster Headache Using Magnetic Resonance Imaging

“…Third, the abnormal FC between the hypothalamus and the midbrain dopaminergic system (in particular the ventral tegmental area) in chronic CH patients ( 18 ) suggests that the possible pathways of chronicization pass through the mesocorticolimbic system also in CH. It is now accepted that the midbrain dopaminergic system is also stimulated by aversive stimuli such as pain ( 61 ), and the nucleus accumbens, a key component of the mesocorticolimbic system receiving direct projections from the ventral tegmental area, seems to be involved in the chronicization of pain in humans ( 62 – 64 ). This possibility in CH is also fostered by the recent proposal of the ventral tegmental area as the main target of DBS ( 65 ) and by the observation that long-term DBS can revert chronic to episodic CH ( 66 ).…”

Surface-based Map Plasticity of the Sensorimotor Cortex in Hip Disorder at Local and Extensive Levels: A Resting-state fMRI Study

“…We also observed that the volume of the nucleus accumbens was signi cantly decreased in the ONFH patients compared with the healthy controls. Makary MM et al 42 provided evidence that a lower nucleus accumbens volume confers risk for developing chronic pain and that altered nucleus accumbens activity is a signature of the state of chronic pain.…”