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

S. M. Carlton, S. Zhou, B. Kraemer, R. E. Coggeshall

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)499-508
Number of pages10
Issue number2
StatePublished - Aug 22 2003
Externally publishedYes


  • Complete Freund's adjuvant
  • Cyclo-somatostatin
  • DNIC
  • Diffuse noxious inhibitory controls
  • Endogenous analgesia
  • Non-opioid

ASJC Scopus subject areas

  • Neuroscience(all)


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