A role for peripheral somatostatin receptors in counter-irritation-induced analgesia

• Published in: Neuroscience 2003-01, Vol.120 (2), p.499-508
• Main Authors: Carlton, S.M, Zhou, S, Kraemer, B, Coggeshall, R.E
• Format: Article
• Language: English
• Subjects: Analgesia; Animals; Behavior, Animal; Biological and medical sciences; Capsaicin - adverse effects; Cell Count; complete Freund's adjuvant; cyclo-somatostatin; diffuse noxious inhibitory controls; DNIC; Drug Administration Routes - veterinary; Drug Interactions; endogenous analgesia; Formaldehyde; Freund's Adjuvant; Fundamental and applied biological sciences. Psychology; Male; Microscopy, Electron - instrumentation; Microscopy, Electron - methods; non-opioid; Pain - chemically induced; Pain - metabolism; Pain - physiopathology; Pain - prevention & control; Pain Measurement - drug effects; Peptides - immunology; Peptides - metabolism; Peptides, Cyclic - pharmacology; Peripheral Nerves - drug effects; Peripheral Nerves - ultrastructure; Physical Stimulation - methods; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin - antagonists & inhibitors; Receptors, Somatostatin - immunology; Receptors, Somatostatin - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00337-3

Our hypothesis is that peripheral somatostatin (SRIF) has a role in counter-irritation-induced analgesia. Our paradigm involves the reduction of nociceptive behaviors produced by primary noxious stimuli (formalin or complete Freund's adjuvant [CFA] in the rat hind paw) by a counter-irritating stimulus (capsaicin [CAP] in the tail or muzzle). Activation of peripheral SRIF receptors is key since an SRIF receptor antagonist cyclo-somatostatin (c-SOM) and SRIF antibodies in the hind paw attenuate the counter-irritation-induced analgesia of both formalin and more persistent CFA nociception. Specificity of c-SOM is shown by reversal of its effects with octreotide, a SRIF analog. Injection of formalin in one hind paw and c-SOM in the other does not reduce the counter-irritation analgesia demonstrating local action of the c-SOM. Approximately 33% of peripheral sensory axons contain SRIF, which could release the peptide to activate SRIF receptors on cutaneous axons. Intraplantar naloxone has no effect on the counter-irritation analgesia indicating that SRIF is not activating opioid receptors. These results indicate that in addition to the classic central descending noxious inhibitory control systems that underlie counter-irritation-induced analgesia, there is a peripheral contribution arising from activation of SRIF receptors. Identifying a peripheral contribution of SRIF to mechanisms of counter-irritation analgesia offers opportunities for peripheral therapy.