Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel

Susan M. Carlton, Shengtai Zhou, Junhui Du, Gregory L. Hargett, Guangchen Ji, Richard E. Coggeshall

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Activation of peripheral somatostatin receptors (SSTRs) inhibits sensitization of nociceptors, thus having a short term or phasic effect [Pain 90 (2001) 233] as well as maintaining a tonic inhibitory control over nociceptors [J Neurosci 21 (2001) 4042]. The present study provides several lines of evidence that an important mechanism underlying SSTR modulation of nociceptors is regulation of the transient receptor potential vanilloid 1 ion channel (TRPV1, formerly the VR1 receptor). Double labeling of L5 dorsal root ganglion cells demonstrates that ∼60% of SSTR2a-labeled cells are positive for TRPV1. Conversely, ∼33% of TRPV1-labeled cells are positive for SSTR2a. In vivo behavioral studies demonstrate that intraplantar injection of 20.0 but not 2.0 μM octreotide (OCT, SSTR agonist) significantly reduces capsaicin (CAP, a ligand for TRPV1) -induced flinching and lifting/licking behaviors. This occurs through local activation of SSTRs in the injected hindpaw and is reversed following co-application of the SSTR antagonist cyclo-somatostatin (c-SOM). In vitro studies using a skin-nerve preparation demonstrate that activation of peripheral SSTRs on nociceptors with 20.0 μM OCT significantly reduces CAP-induced activity and can prevent CAP-induced desensitization. Furthermore, blockade of peripheral SSTRs with c-SOM dramatically enhances CAP-induced behaviors and nociceptor activity, demonstrating SSTR-induced tonic inhibitory modulation of TRPV1. Finally, TRPV1 does not appear to be under tonic opioid receptor control since the opioid antagonist naloxone does not change CAP-induced excitation and does not effect OCT-induced inhibition of CAP responses. These data strongly suggest that SSTRs modulate nociceptors through phasic and tonic regulation of peripheral TRPV1 receptors.

Original languageEnglish (US)
Pages (from-to)616-627
Number of pages12
JournalPain
Volume110
Issue number3
DOIs
StatePublished - Aug 1 2004

Keywords

  • Capsaicin
  • Hyperalgesia
  • Nociception
  • Primary afferent
  • Somatostatin
  • VR1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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    Carlton, S. M., Zhou, S., Du, J., Hargett, G. L., Ji, G., & Coggeshall, R. E. (2004). Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel. Pain, 110(3), 616-627. https://doi.org/10.1016/j.pain.2004.04.042