Sensation of TRPV1 via 5-hydroxytryptamine signaling modulates pain hypersensitivity in a 6-hydroxydopamine induced mice model of Parkinson's disease

Biochem Biophys Res Commun. 2020 Jan 22;521(4):868-873. doi: 10.1016/j.bbrc.2019.10.204. Epub 2019 Nov 7.

Abstract

Parkinson's disease (PD) related pain can be assigned to either nociceptive pain or neuropathic pain, in which Transient receptor potential vanilloid 1 (TRPV1) has been demonstrated to play a pivotal role. Yet little research has examined possible involvement of TRPV1 in pain in PD. Here, we show that TRPV1 is highly expressed in PD and blocking TRPV1 can alleviate pain in PD. The level of TRPV1 in 6-OHDA induced semi mice model of PD was evaluated. The effect of TRPV1 and involved serotonin (5-HT) was also examined in the model. Unilateral injection of 6-OHDA in striatum significantly decreased thermal pain threshold and induced mechanical allodynia without changes in conditioned place preference. Immunostaining revealed that great increased expression in TRPV1 in the Vc of 6-OHDA lesioned mice compared with sham mice. TRPV1 sensitization was maintained by 5-HT/5-HT3A. In 6-OHDA-lesioned mice model of PD, TRPV1 sensitization might be implicated in the maintenance of behavioral hypersensitivity by enhanced descending 5-HT pain facilitation and dorsal horn 5-HT3AR mechanism.

Keywords: Pain; Parkinson’s disease; Serotonin; Transient receptor potential vanilloid 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Disease Models, Animal
  • Hyperalgesia / etiology*
  • Hyperalgesia / metabolism
  • Male
  • Mice, Inbred C57BL
  • Oxidopamine / toxicity
  • Pain Threshold
  • Parkinson Disease / etiology*
  • Piperidines / pharmacology
  • Receptors, Serotonin, 5-HT3 / metabolism
  • Serotonin / metabolism*
  • Signal Transduction
  • TRPV Cation Channels / metabolism*
  • Trigeminal Caudal Nucleus / metabolism*

Substances

  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acrylamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Piperidines
  • Receptors, Serotonin, 5-HT3
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Serotonin
  • Oxidopamine
  • 4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride