Suppression of Wnt5a, but not Wnts, relieves chronic post-thoracotomy pain via anti-inflammatory modulation in rats

Biochem Biophys Res Commun. 2017 Nov 4;493(1):474-480. doi: 10.1016/j.bbrc.2017.08.167. Epub 2017 Sep 4.

Abstract

With regard to post-surgical pain, the incidence of chronic post-thoracotomy pain (CPTP) is second only to that caused by amputation and the underlying mechanism remains elusive. The emerging role of Wnts has been confirmed in the pathogenesis of neuropathic and inflammatory pain, both of which are known components of CPTP. We investigated whether Wnt3a and Wnt5a were involved in the development of CPTP, concerning their regulation of inflammatory responses in a previously established rat model. We observed up regulated protein levels of Wnt3a, Wnt5a, β-catenin, and TLR4, along with activated astrocytes and pro-inflammatory cytokines, in both dorsal root ganglia and the spinal cord dorsal horn. Furthermore, intrathecal inhibition of Wnt5a but not Wnts relieved mechanical hyperalgesia, down regulated expression of TLR4, and inactivated astrocytes and pro-inflammatory cytokines. These results suggest Wnt5a, but not Wnts, contributes to the development of CPTP, possibly by regulating the inflammatory response.

Keywords: Chronic post-thoracotomy pain; Inflammation; TLR4; Wnt5a; Wnts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Pain / etiology
  • Chronic Pain / immunology*
  • Chronic Pain / prevention & control*
  • Immunologic Factors / immunology
  • Male
  • Pain, Postoperative / immunology*
  • Pain, Postoperative / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Thoracotomy / adverse effects*
  • Wnt Proteins / immunology
  • Wnt-5a Protein / immunology*

Substances

  • Immunologic Factors
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, rat