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• W2131306809 abstract "Tibia fracture followed by limb immobilization in rats evokes nociceptive and vascular changes resembling complex regional pain syndrome type I (CRPS I). Previously we observed that substance P (SP) and interleukin-1β (IL-1β) signaling contribute to chronic regional nociceptive sensitization in this model. It is known that inflammasome multi-protein complexes containing caspase-1 and NALP1 are involved in the activation of the IL-1β family of pro-nociceptive cytokines expressed in skin and other tissues. Therefore, we hypothesized that SP activated inflammasomes might contribute to mechanical allodynia after fracture. Using this model we observed that: (1) inflammasome components and products NALP1, caspase-1, IL-1β and IL-18 were present in low levels in normal skin, but expression of all these was strongly up-regulated after fracture, (2) NALP1, caspase-1 and IL-1β were co-expressed in keratinocytes, and the number of NALP1, caspase-1, and IL-1β positive cells dramatically increased at 4 weeks post-fracture, (3) LY303870, an NK1 receptor antagonist, effectively blocked fracture-induced up-regulation of activated inflammasome components and cytokines, (4) IL-1β and IL-18 intraplantar injection induced mechanical allodynia in normal rats, and (5) both a selective caspase-1 inhibitor and an IL-1 receptor antagonist attenuated fracture-induced hindpaw mechanical allodynia. Collectively, these data suggest that NALP1 containing inflammasomes activated by NK1 receptors are expressed in keratinocytes and contribute to post-traumatic regional nociceptive sensitization. These findings highlight the possible importance of neuro-cutaneous signaling and innate immunity mechanisms in the development of CRPS." @default.
• W2131306809 created "2016-06-24" @default.
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• W2131306809 date "2009-12-01" @default.
• W2131306809 modified "2023-10-17" @default.
• W2131306809 title "The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome" @default.
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• W2131306809 doi "https://doi.org/10.1016/j.pain.2009.09.032" @default.
• W2131306809 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5515229" @default.
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• W2131306809 hasPublicationYear "2009" @default.
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