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

Pain. 2004 Aug;110(3):616-627. doi: 10.1016/j.pain.2004.04.042.


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 approximately 60% of SSTR2a-labeled cells are positive for TRPV1. Conversely, approximately 33% of TRPV1-labeled cells are positive for SSTR2a. In vivo behavioral studies demonstrate that intraplantar injection of 20.0 but not 2.0 microM 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 microM 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Capsaicin / pharmacology*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology
  • Ion Channels / agonists
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / physiology
  • Male
  • Motor Activity
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / physiology*
  • Somatostatin / pharmacology*
  • Somatostatin / physiology


  • Ion Channels
  • Receptors, Drug
  • Somatostatin
  • Capsaicin