Caspase-11 contributes to pain hypersensitivity in the later phase of CFA-induced pain of mice

Brain Res. 2023 Feb 15:1801:148172. doi: 10.1016/j.brainres.2022.148172. Epub 2022 Nov 18.

Abstract

Chronic pain is a common disease that severely disrupts the quality of life. Persistent neuroinflammation and central sensitization play important roles in its pathogenesis. Caspase-11 is a critical modulator of inflammation of central nervous system. However, its role in chronic pain remains elusive. In this study, chronic pain and acute pain were induced via injecting complete Freund's adjuvant (CFA) and 5 % formalin into the plantar of the right hind paw of wild-type (WT) and Caspase-11 deficient (Caspase-11-/-) mice, respectively. In WT mice, CFA injection significantly decreased the hind paw mechanical pain threshold in Von Frey test on 1-7 days after injection and increased the caspase-11 level of ipsilateral dorsal horn of spinal cord on day 2 and day 5 after injection. Compared to the WT mice, Caspase-11-/- mice showed significantly higher mechanical pain threshold in the later phase of CFA-induced pain, but not in the early phase, and had no significant difference in 5 % formalin induced licking and flinching behavior. In addition, the microglial activation, and the mRNA levels of caspase-1 and IL-18 in the spinal cord of Caspase-11-/- mice restored to baseline on the day 5 after CFA injection, but not in WT mice. Our data indicated that Caspase-11 contributed to persistent inflammation in ipsilateral dorsal horn of spinal cord, and consequently pain hypersensitivity in the later phase of CFA-induced pain.

Keywords: CFA; Caspase-11; Inflammatory pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Pain*
  • Formaldehyde
  • Freund's Adjuvant / adverse effects
  • Hyperalgesia / chemically induced
  • Hypersensitivity*
  • Inflammation / chemically induced
  • Mice
  • Quality of Life
  • Spinal Cord
  • Spinal Cord Dorsal Horn

Substances

  • Formaldehyde
  • Freund's Adjuvant
  • Casp4 protein, mouse