Targeting 5-HT2A receptors and Kv7 channels in PFC to attenuate chronic neuropathic pain in rats using a spared nerve injury model

Velia S. Vizcarra, Kara R. Barber, Gabriela Franca-Solomon, Lisa Majuta, Angela Smith, Paul R. Langlais, Tally M. Largent-Milnes, Todd W. Vanderah, Arthur C. Riegel

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Chronic pain remains a disabling disease with limited therapeutic options. Pyramidal neurons in the prefrontal cortex (PFC) express excitatory Gq-coupled 5-HT2A receptors (5-HT2AR) and their effector system, the inhibitory Kv7 ion channel. While recent publications show these cells innervate brainstem regions important for regulating pain, the cellular mechanisms underlying the transition to chronic pain are not well understood. The present study examined whether local blockade of 5-HT2AR or enhanced Kv7 ion channel activity in the PFC would attenuate mechanical allodynia associated with spared nerve injury (SNI) in rats. Following SNI, we show that inhibition of PFC 5-HT2ARs with M100907 or opening of PFC Kv7 channels with retigabine reduced mechanical allodynia. Parallel proteomic and RNAScope experiments evaluated 5-HT2AR/Kv7 channel protein and mRNA. Our results support the role of 5-HT2ARs and Kv7 channels in the PFC in the maintenance of chronic pain.

Original languageEnglish (US)
Article number136864
JournalNeuroscience Letters
Volume789
DOIs
StatePublished - Oct 15 2022

Keywords

  • 5-HTR
  • Kv7 ion channels
  • Pain
  • Prelimbic cortex
  • Retigabine
  • Spared nerve injury (SNI)

ASJC Scopus subject areas

  • General Neuroscience

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