Pain
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To characterize the contribution of interleukin-6 (IL-6) to spinal cord injury pain (SCIP), we employed a clinically relevant rat contusion model of SCIP. Using Western blots, we measured IL-6 levels in lumbar segments (L1-L5), at the lesion site (T10), and in the corresponding lumbar and thoracic dorsal root ganglia (DRG) in 2 groups of similarly injured rats: (a) SCI rats that developed hind-limb mechanical allodynia (SCIP), and (b) SCI rats that did not develop SCIP. Only in SCIP rats did we find significantly increased IL-6 levels. ⋯ We also showed that IL-6-R Ab partially reversed SCI-induced decreases in the protein levels of the glutamate transporter GLT-1 12hours and 8days after Ab injection, which may explain the lasting analgesic effect of the Ab in SCIP rats. A link between reactive astrocytes IL-6-GLT-1 has not been previously shown. Given that the humanized IL-6-R Ab tocilizumab is Food and Drug Administration-approved for rheumatoid arthritis, we are proposing tocilizumab as a novel and potentially effective treatment for SCIP.
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Comparative Study Controlled Clinical Trial
Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain.
Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. ⋯ BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS.
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Randomized Controlled Trial Multicenter Study
Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: a randomized, multicenter, double-blind, crossover, sham-controlled trial.
There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. ⋯ There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.