Neural correlates of chronic low back pain measured by arterial spin labeling

Abstract

Background: The varying nature of chronic pain (CP) is difficult to correlate to neural activity using typical functional magnetic resonance imaging methods. Arterial spin labeling is a perfusion-based imaging technique allowing the absolute quantification of regional cerebral blood flow, which is a surrogate measure of neuronal activity.

Methods: Subjects with chronic low back and radicular pain and matched healthy normal subjects, undergoing identical procedures, participated in three sessions: a characterization and training session and two arterial spin labeling sessions. In the first imaging session, CP (if any) was exacerbated using clinical maneuvers; in the second session, noxious heat was applied to the affected leg dermatome, the intensity of which was matched to the pain intensity level of the CP exacerbations for each back pain subject.

Results: The clinically significant worsening of ongoing CP (≤ 30%, n = 16) was associated with significant regional blood flow increases (6-10 mm/100 g of tissue/min, P less than 0.01) within brain regions known to activate with experimental pain (somatosensory, prefrontal, and insular cortices) and in other structures observed less frequently in experimental pain studies, such as the superior parietal lobule (part of the dorsal attention network). This effect is specific to changes in ongoing CP as it is observed during worsening CP, but it is not observed after thermal pain application, or in matched, pain-free healthy controls.

Conclusions: Study findings demonstrate the use of arterial spin labeling to investigate the neural processing of CP, and these findings are a step forward in the quest for objective biomarkers of the chronic pain experience.

Figures

Figure 1

Study Design ASL=arterial spin labeling, gr=grams, min=minute, ml=milliliters, M0=the longitudinal magnetization of fully relaxed tissue scan, rCBF=regional cerebral blood flow, s=seconds,

Figure 2

Mean ratings of baseline clinical pain in chronic low back pain patients (0–20 Gracely Box Scale). Ratings were obtained in-between pain stimulations (~1min after the end of the preceding heat or clinical maneuver). Bars represent group averages (±SEM) of the following: pASL1,2= ratings before and after each pASL scan (2 ratings per timepoint); Run1–3= ratings within each run (4 ratings per timepoint). pASL=pulsed arterial spin labeling, SEM=standard error of the mean

Figure 3

Significant clusters on inflated brain maps showing significant mean changes in rCBF for the clinical maneuvers (Panel A, bilateral: prefrontal cortices, S1, S2, SPL, and right insula, p<.01 and heat pain sessions in the clbp subjects clinical maneuvers session healthy normal b low back dlpfc="dorsolateral" prefrontal cortex m1="primary" motor mpfc="medial" presma="pre-supplementary" area rcbf="regional" cerebral blood flow s1="primary" somatosensory s2="secondary">

Figure 4

Significant clusters of activation on inflated brain maps for the subtraction comparison of CLBP subjects vs. healthy controls for the clinical maneuvers session (Panel A vs. Panel B, left SPL, S1, M1). ASL=arterial spin labeling, CLBP=chronic low back pain, HC=healthy controls, M1=primary motor cortex, S1=primary somatosensory cortex, SPL=superior parietal lobule

Figure 5

The mean changes in rCBF in the activation clusters across all sessions. For the clinical maneuvers session in the CLBP subjects, these areas had a 17–25% increase in rCBF. For all comparisons to the clinical maneuvers session, p<.01. ains="anterior" insula asl="arterial" spin labeling bil="bilateral," clbp="chronic" low back pain ctrl="control," gr="grams," hc="healthy" controls l="left" side m1="primary" motor cortex mfg="medial" frontal gyrus min="minute," ml="milliliters," mpfc="medial" prefrontal presma="pre-supplementary" area r="right" rcbf="regional" cerebral blood flow s1="primary" somatosensory s2="secondary" smg="superior" marginal spl="superior" parietal lobule>