Resolvin D1 attenuates mechanical allodynia after burn injury: Involvement of spinal glia, p38 mitogen-activated protein kinase, and brain-derived neurotrophic factor/tropomyosin-related kinase B signaling

Mol Pain. 2023 Jan-Dec:19:17448069231159970. doi: 10.1177/17448069231159970.

Abstract

Resolvin D1 (RvD1) suppresses inflammatory, postoperative, and neuropathic pain. The present study assessed the roles and mechanisms of RvD1 in mechanical allodynia after burn injury. A rat model of burn injury was established for analyses, and RvD1 was injected intraperitoneally. Pain behavior and the expression levels of spinal dorsal horn Iba-1 (microglia marker), GFAP (astrocyte marker), p-p38 mitogen-activated protein kinase (MAPK), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) were detected by behavioral and immunocytochemical assays. The results showed that RvD1 attenuated mechanical allodynia after burn injury, prevented microglial and astroglial activation, and downregulated p-p38 MAPK in microglia and BDNF/TrkB following burn injury. Similarly, inhibition of p38 MAPK and BDNF/TrkB signaling attenuated mechanical allodynia after burn injury. In addition, inhibition of p38 MAPK prevented spinal microglial activation and downregulated BDNF/TrkB following burn injury. Furthermore, inhibition of BDNF/TrkB signaling prevented spinal microglial activation and downregulated p-p38 MAPK within spinal microglia. Taken together, this study demonstrated that RvD1 might attenuate mechanical allodynia after burn injury by inhibiting spinal cord glial activation, microglial p38 MAPK, and BDNF/TrkB signaling in the spinal dorsal horn.

Keywords: BDNF/TrkB; RvD1; astrocytes; mechanical allodynia after burn injury; microglia; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Burns* / complications
  • Burns* / drug therapy
  • Hyperalgesia* / drug therapy
  • Hyperalgesia* / etiology
  • Hyperalgesia* / metabolism
  • Microglia / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Dorsal Horn / metabolism
  • Tropomyosin / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases
  • Brain-Derived Neurotrophic Factor
  • resolvin D1
  • Tropomyosin