RGD Reference Report - The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome. - Rat Genome Database

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The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome.

Authors: Li, WW  Guo, TZ  Liang, D  Shi, X  Wei, T  Kingery, WS  Clark, JD 
Citation: Li WW, etal., Pain. 2009 Dec 15;147(1-3):277-86. Epub 2009 Oct 22.
RGD ID: 2315887
Pubmed: PMID:19853379   (View Abstract at PubMed)
PMCID: PMC5515229   (View Article at PubMed Central)
DOI: DOI:10.1016/j.pain.2009.09.032   (Journal Full-text)

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-1beta (IL-1beta) 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-1beta 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-1beta 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-1beta were co-expressed in keratinocytes, and the number of NALP1, caspase-1, and IL-1beta 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-1beta 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CASP1HumanPain  ISOCasp1 (Rattus norvegicus) RGD 
Casp1RatPain  IMP  RGD 
Casp1MousePain  ISOCasp1 (Rattus norvegicus) RGD 
IL18HumanPain  ISOIl18 (Rattus norvegicus) RGD 
Il18RatPain  IDA  RGD 
Il18MousePain  ISOIl18 (Rattus norvegicus) RGD 
CASP1HumanTibial Fractures  ISOCasp1 (Rattus norvegicus) RGD 
Casp1MouseTibial Fractures  ISOCasp1 (Rattus norvegicus) RGD 
Casp1RatTibial Fractures  IEP  RGD 
IL18HumanTibial Fractures  ISOIl18 (Rattus norvegicus)protein:increased expression:skinRGD 
Il18RatTibial Fractures  IEP protein:increased expression:skinRGD 
Il18MouseTibial Fractures  ISOIl18 (Rattus norvegicus)protein:increased expression:skinRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Il18Ratdetection of mechanical stimulus involved in sensory perception of pain  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp1  (caspase 1)
Il18  (interleukin 18)

Genes (Mus musculus)
Casp1  (caspase 1)
Il18  (interleukin 18)

Genes (Homo sapiens)
CASP1  (caspase 1)
IL18  (interleukin 18)


Additional Information