Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel.
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.
Department of Anatomy and Neurosciences, Marine Biomedical Institute, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1069, USA.
Susan M
SM
Carlton
Shengtai
S
Zhou
Junhui
J
Du
Gregory L
GL
Hargett
Guangchen
G
Ji
Richard E
RE
Coggeshall
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology* / Q000502:physiology
D007473:Ion Channels; D011955:Receptors, Drug; D013004:Somatostatin; D002211:Capsaicin