Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: In vitro and in vivo studies in rat

G. C. Ji, S. T. Zhou, G. Shapiro, J. C. Reubi, S. M. Carlton, Simona Jurczyk

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Several lines of evidence support an important role for somatostatin receptors (SSTRs) in pain modulation. The therapeutic use of established SSTR peptide agonists for this indication is limited by their broad range of effects, need for intrathecal delivery, and short half-life. Therefore, the goal of the present study was to investigate the analgesic effect of SCR007, a new, highly selective SSTR2 non-peptide agonist. Behavioral studies demonstrated that paw withdrawal latencies to heat were significantly increased following intraplantar SCR007. Furthermore, both intraperitoneal and intraplantar injection of SCR007 significantly reduced formalin- and capsaicin-induced flinching and lifting/licking nociceptive behaviors. Recordings from nociceptors using an in vitro glabrous skin-nerve preparation showed that SCR007 reduced heat responses in a dose-dependent fashion, bradykinin-induced excitation, heat sensitization and capsaicin-induced excitation. In both the behavioral and single fiber studies, the SCR007 effects were reversed by the SSTR antagonist cyclo-somatostatin, demonstrating receptor specificity. In the single fiber studies, the opioid antagonist naloxone did not reverse SCR007-induced anti-nociception suggesting that SCR007 did not exert its effects through activation of opioid receptors. Analysis of cAMP/protein kinase A (PKA) involvement demonstrated that SCR007 prevented forskolin- and Sp-8-Br-cAMPS (a PKA activator)-induced heat sensitization, supporting the hypothesis that SCR007-induced inhibition could involve a down-regulation of the cAMP/PKA pathway. These data provide several lines of evidence that the non-peptide imidazolidinedione SSTR2 agonist SCR007 is a promising anti-nociceptive and analgesic agent for the treatment of pain of peripheral and/or central origin.

Original languageEnglish (US)
Pages (from-to)34-49
Number of pages16
JournalPain
Volume124
Issue number1-2
DOIs
StatePublished - Sep 2006

Fingerprint

Somatostatin
Analgesics
Somatostatin Receptors
Cyclic AMP-Dependent Protein Kinases
Hot Temperature
Capsaicin
SCR007
In Vitro Techniques
Pain
Nociceptors
Nociception
Narcotic Antagonists
Opioid Receptors
Bradykinin
Therapeutic Uses
Colforsin
Naloxone
Intraperitoneal Injections
Formaldehyde
Half-Life

Keywords

  • Analgesia
  • Anti-nociception
  • Capsaicin
  • Inflammation
  • Inflammatory pain
  • Peripheral sensitization

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Ji, G. C., Zhou, S. T., Shapiro, G., Reubi, J. C., Carlton, S. M., & Jurczyk, S. (2006). Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: In vitro and in vivo studies in rat. Pain, 124(1-2), 34-49. https://doi.org/10.1016/j.pain.2006.03.014

Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist : In vitro and in vivo studies in rat. / Ji, G. C.; Zhou, S. T.; Shapiro, G.; Reubi, J. C.; Carlton, S. M.; Jurczyk, Simona.

In: Pain, Vol. 124, No. 1-2, 09.2006, p. 34-49.

Research output: Contribution to journalArticle

Ji, GC, Zhou, ST, Shapiro, G, Reubi, JC, Carlton, SM & Jurczyk, S 2006, 'Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist: In vitro and in vivo studies in rat', Pain, vol. 124, no. 1-2, pp. 34-49. https://doi.org/10.1016/j.pain.2006.03.014
Ji, G. C. ; Zhou, S. T. ; Shapiro, G. ; Reubi, J. C. ; Carlton, S. M. ; Jurczyk, Simona. / Analgesic activity of a non-peptide imidazolidinedione somatostatin agonist : In vitro and in vivo studies in rat. In: Pain. 2006 ; Vol. 124, No. 1-2. pp. 34-49.
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