Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 132, Issue 8, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI151817
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Funding
- Canadian Institutes of Health Research
- Brain Canada
- Cancer Council New South Wales
- Ronald Melzack Fellowship in Chronic Pain Research from the Louise and Alan Edwards Foundation
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Mice with experimental nerve damage display long-lasting neuropathic pain behavior. Senescence in the spinal cord for 4 months results in the maintenance of pain and a decreased lifespan. Nerve injury increases the number of p53-positive cells in the spinal cord neurons, astrocytes, and microglia, with a male-specific increase observed only in microglia. Repeated administration of a p53-specific substance reverses pain hypersensitivity.
Mice with experimental nerve damage can display long-lasting neuropathic pain behavior. We show here that 4 months senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53-positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male-specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male-specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53-specific relevance of this pathway in humans, featuring male-specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.
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