Role of the NLRP3 inflammasome in a model of acute burn-induced pain

Burns. 2017 Mar;43(2):304-309. doi: 10.1016/j.burns.2016.09.001. Epub 2016 Dec 28.

Abstract

The NLRP3 inflammasome is a multi-protein complex that assembles in response to tissue damage or infection, triggering activation of caspase-1, an enzyme that converts interleukin (IL)-1β into its active form. A role for the NLRP3 inflammasome is emerging in inflammatory pain, but its influence in other pain types is largely unexamined. Therefore the aim of this study was to assess the role of the NLRP3 inflammasome and its downstream product caspase-1 in a model of acute burn-induced pain in male mice. A superficial burn was induced on the plantar surface of the left hind paw using a hot plate set at 52.5°C for 25s. Development of burn-induced mechanical allodynia, thermal allodynia, edema and weight bearing changes was assessed in Nlrp3-/- and caspase-1-deficient (Ice-/-) mice, and in mice administered the selective NLRP3 inflammasome inhibitor MCC950. Burn-induced mechanical and thermal allodynia developed normally in Nlrp3-/- and Ice-/- mice and mice administered MCC950. Burn-induced edema was significantly reduced in Ice-/- mice only. Burn-induced weight bearing changes were attenuated in Nlrp3-/- mice and mice administered MCC950 72h after burn only. This study suggests that NLRP3 and its downstream product caspase-1 have a limited role in the development of burn-induced pain.

Keywords: Burns; Caspase-1; Interleukin-1β; Mouse model; NLRP3 inflammasome; Pain.

MeSH terms

  • Acute Pain / etiology
  • Acute Pain / genetics*
  • Animals
  • Behavior, Animal / drug effects
  • Burns / complications
  • Caspase 1 / genetics*
  • Disease Models, Animal
  • Edema / etiology
  • Edema / genetics*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Hindlimb / injuries
  • Hyperalgesia / etiology
  • Hyperalgesia / genetics*
  • Inflammasomes / antagonists & inhibitors
  • Inflammasomes / genetics*
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Sulfones / pharmacology
  • Weight-Bearing

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • MCC-950
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Sulfones
  • Caspase 1