Botulinum toxin type A reduces TRPV1 expression in the dorsal root ganglion in rats with adjuvant-arthritis pain

Toxicon. 2017 Jul:133:116-122. doi: 10.1016/j.toxicon.2017.05.001. Epub 2017 May 3.

Abstract

Arthritis pain affects people's long-term health, and recent studies have demonstrated that transient receptor potential vanilloid type 1 (TRPV1) plays a crucial role in arthritis pain. In addition, Pre-clinical evidence indicated that botulinum toxin type A (BoNT/A) has antinociceptive effect. The present study investigated the causality between the antinociceptive effects of BoNT/A and the expression of TRPV1 in dorsal root ganglion (DRG) in rats with adjuvant-arthritis pain. The results showed that BoNT/A significantly reduced adjuvant-arthritis nociceptive behaviors in a dose-dependent manner. Furthermore, the BoNT/A cleaved synaptosomal-associated protein of 25 kDa (cl-SNAP-25) was detected in the DRG using immunofluorescence after intra-articular administration. Although BoNT/A significantly reduced the protein levels of TRPV1, there were no significant changes in the mRNA levels of TRPV1 between CFA and BoNT/A (1U, 3U, 10U) group after BoNT/A retrograde axonal transport into the DRG with quantitative RT-PCR. This research provides evidence that the antinociceptive mechanism of BoNT/A might be mediated by reduction of TRPV1 expression through inhibition of its plasma membrane trafficking after intra-articular administration.

Keywords: Arthritis pain; Botulinum toxin type A; Dorsal root ganglion; Retrograde axonal transport; Transient receptor potential vanilloid type 1.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Arthritis, Experimental / drug therapy
  • Botulinum Toxins, Type A / pharmacology*
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Male
  • Pain / drug therapy*
  • Pain / metabolism
  • RNA, Messenger
  • Rats, Sprague-Dawley
  • Synaptosomal-Associated Protein 25 / metabolism
  • TRPV Cation Channels / metabolism*

Substances

  • Adjuvants, Immunologic
  • RNA, Messenger
  • Synaptosomal-Associated Protein 25
  • TRPV Cation Channels
  • TRPV1 receptor
  • Botulinum Toxins, Type A