Pain
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Neuropathic pain after spinal cord injury is not well understood and is difficult to treat. One possible cause is mismatch between motor commands and sensory feedback. This two-part study in five paraplegic patients investigated whether a visual illusion aimed to correct this mismatch reduces pain. ⋯ Mean (95% CI) decrease in pain was 53 mm (45-61 mm) at post training and 43 mm (27-58 mm) at 3-month follow-up. Virtual walking may be a viable treatment for pain after spinal cord injury. A clinical trial seems warranted.
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Using a gene expression analysis approach we found that the mRNA encoding the lysosomal cysteine protease cathepsin S (CatS) was up-regulated in rat dorsal root ganglia (DRG) following peripheral nerve injury. CatS protein was expressed in infiltrating macrophages in DRG and near the site of injury. At both sites CatS expression progressively increased from day 3 to day 14 after injury. ⋯ In nerve-injured rats, mechanical hyperalgesia, but not allodynia, was significantly reversed for up to 3h by systemic administration of a non-brain penetrant, irreversible CatS inhibitor (LHVS, 3-30 mg/kg s.c.). Depletion of peripheral macrophages by intravenous injection of liposome encapsulate clodronate (1ml, 5 mg/ml) partially reduced established mechanical hyperalgesia but not allodynia, and abolished the anti-hyperalgesic effect of LHVS. Our results demonstrate a pro-nociceptive effect of CatS and indicate that endogenous CatS released by peripheral macrophages contributes to the maintenance of neuropathic hyperalgesia following nerve injury.