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

• Published in: Pain (Amsterdam) Vol. 110; no. 3; pp. 616 - 627
• Main Authors: Carlton, Susan M, Zhou, Shengtai, Du, Junhui, Hargett, Gregory L, Ji, Guangchen, Coggeshall, Richard E
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2004; Elsevier
• Subjects: Animals; Biological and medical sciences; Capsaicin; Capsaicin - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiology; Hyperalgesia; Ion Channels - agonists; Ion Channels - antagonists & inhibitors; Ion Channels - physiology; Male; Motor Activity; Nociception; Primary afferent; Rats; Rats, Sprague-Dawley; Receptors, Drug - agonists; Receptors, Drug - antagonists & inhibitors; Receptors, Drug - physiology; Somatostatin; Somatostatin - pharmacology; Somatostatin - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; VR1; Nociception; Primary afferent; Somatostatin; VR1; Capsaicin; Hyperalgesia; Spinal cord; Somatostatin receptor; Central nervous system; Ionic channel; Neuropeptide; Nociceptor; TRPV1 vanilloid receptor; Pain; Modulation; Spinal ganglion; Sensitization; Vanilloid receptor
• ISSN: 0304-3959; 1872-6623
• 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 ∼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.