No 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 2=0.71, α=0.97). Although myoinositol predicted loss of EPM in the ACC (P=0.04), this was below statistical power (r 2=0.31; α=0.56). The ACC N-acetyl-aspartate/myoinositol ratio (P=0.006) predicted chronic pain (DN4, r 2=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.

Humans, primates, and rodents with cervical spinal cord injury (SCI) show permanent sensorimotor dysfunction of the upper/fore limb as consequence of axonal damage and local neuronal death. This work aimed at characterizing a model of cervical SCI in domestic pigs in which hemisection with excision of one centimeter of spinal cord was performed to reproduce the loss of neural tissue observed in human neuropathology. Posture and motor control were assessed over 3 months by scales and kinematics of treadmill locomotion.Histological measurements included lesion length, atrophy of the adjacent spinal cord segments, and neuronal death. In some animals, the retrograde neural tracer aminostilbamidine was injected in segments caudal to the lesion to visualize propriospinal projection neurons. Neuronal loss extended for 4-6 mm from the lesion borders and was more severe in the ipsilateral, caudal spinal cord stump. Axonal Wallerian degeneration was observed caudally and rostrally, associated to marked atrophy of the white matter in the spinal cord segments adjacent to the lesion. The pigs showed chronic monoplegia or severe monoparesis of the foreleg ipsilateral to the lesion, whereas the trunk and the other legs had postural and motor impairments that substantially improved during the first month postlesion. Adaptations of the walking cycle like those reported for rats and humans ameliorated the negative impact of focal neurological deficits on locomotor performance. These results provide a baseline of behavior and histology in a porcine model of cervical spinal cord hemisection that can be used for translational research in SCI therapeutics.