Pain
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Randomized Controlled Trial
Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats.
In this study, we examined whether blocking spinal cord injury (SCI)-induced increases in reactive oxygen species (ROS) by a ROS scavenger would attenuate below-level central neuropathic pain and promote recovery of locomotion. Rats with T10 SCI developed mechanical allodynia in both hind paws and overproduction of ROS, as assayed by Dhet intensity, in neurons in the lumbar 4/5 dorsal horn ((∗)P<0.05). To scavenge ROS, phenyl-N-tert-butylnitrone (PBN, a ROS scavenger) was administered immediately after SCI and for 7 consecutive days (early treatment) by either intrathecal (it; 1 and 3mg) or systemic (ip; 10, 50 and 100mg) injections. ⋯ Both SCI and t-BOOH treatment groups showed significantly increased phospho-CamKII (pCamKII) expression in neurons and KN-93 (an inhibitor of pCamKII) significantly attenuated mechanical allodynia ((∗)P<0.05). In addition, high doses of PBN significantly promoted the recovery of locomotion ((∗)P<0.05). In conclusion, the present data suggest that overproduction of ROS contribute to sensory and motor abnormalities in remote segments below the lesion after thoracic SCI.
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Sciatica after disc herniation may be associated with compression of spinal nerves, but also inflammatory substances released from the nucleus pulposus (NP) leaking into the spinal canal. Here, in an animal model mimicking clinical intervertebral disc herniation, we investigate the effect of NP on neuronal activity. In anaesthetized Lewis rats, extracellular single-unit recordings of spinal dorsal horn neurons were performed, and the C-fibre responses were examined. ⋯ In accordance with earlier studies, we showed a significant increase in the C-fibre response and an upregulation of the gene expression of interleukin 1β and tumour necrosis factor 180 minutes after application of NP onto the nerve roots. Moreover, based on a polymerase chain reaction array of 84 common inflammatory cytokines at the same time point, we demonstrated a highly significant upregulation of colony-stimulating factor 1 also termed macrophage colony-stimulating factor and Fas ligand. The pronounced upregulation of Csf1 and Fas ligand 180 minutes after application of NP onto the nerve roots suggests that macrophage activation and apoptosis may be involved in pain hypersensitivity and other sensory abnormalities after disc herniation.