Deficient Inhibitory Endogenous Pain Modulation Correlates With Periaqueductal Gray Matter Metabolites During Chronic Whiplash Injury.

ABSTRACT

OBJECTIVES: This study examined predictive correlations between periaqueductal gray (PAG) and anterior cingulate cortex (ACC) metabolite levels with deficient inhibitory endogenous pain modulation (EPM), including sensory and affective measures of pain during chronic whiplash injury (WHI). MATERIALS AND METHODS: Healthy patients, and participants with chronic WHI, without (WHI-noP) or with pain (WHI-P), were screened with the Douleur Neuropathique 4 tool (DN4). EPM was assessed with C6 tonic heat pain stimuli with a Conditioned Pain Modulation (CPM) protocol. Magnetic resonance spectroscopy quantified ACC and PAG metabolite levels. RESULTS: WHI-P participants were characterized with high pain intensity and interference, and lower quality of life scores, compared with WHI-noP. Inhibitory CPM at 30 seconds was identified in the healthy noninjured (-45±16%; P<0.001) and WHI-noP groups (-36±8%; P<0.001). However, inhibitory EPM was not detected in the WHI-P group (-25±15%; P=0.06). Best fit and stepwise multiple regression revealed that the PAG glutamate/myoinositol metabolite ratio (P=0.01) and total creatine levels (P=0.02) predicted loss of EPM in the WHI-P group (r=0.71, α=0.97). Although myoinositol predicted loss of EPM in the ACC (P=0.04), this was below statistical power (r=0.31; α=0.56). The ACC N-acetyl-aspartate/myoinositol ratio (P=0.006) predicted chronic pain (DN4, r=0.53; α=0.87). DISCUSSION: The results of this study demonstrate deficient EPM at 30 seconds during tonic heat pain stimulation in WHI-P participants, compared with noninjured healthy volunteers or individuals with WHI-noP. In addition, quantification of PAG and ACC metabolites related to glutamate and glia predicted central chronic pain mechanisms related to loss of inhibitory EPM, while ACC metabolites characterized chronic pain described by descriptors and sensory changes.