A role for peripheral somatostatin receptors in counter-irritation-induced analgesia.
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.
Carlton
S M
SM
Department of Anatomy and Neurosciences, Marine Biomedical Institute, 301 University Boulevard, University of Texas Medical Branch, Galveston, TX 77555-1069, USA. smcarlto@utmb.edu
Zhou
S
S
Kraemer
B
B
Coggeshall
R E
RE
D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000009:adverse effects; D002452:Cell Count; D004333:Drug Administration Routes / Q000662:veterinary; D004347:Drug Interactions; D005557:Formaldehyde; D005620:Freund's Adjuvant; D008297:Male; D008854:Microscopy, Electron / Q000295:instrumentation / Q000379:methods; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000648:ultrastructure; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D013997:Time Factors
D010455:Peptides; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C067675:cyclosomatostatin; D005557:Formaldehyde; D005620:Freund's Adjuvant; D002211:Capsaicin