HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Analgesic effect of TT-232, a heptapeptide somatostatin analogue, in acute pain models of the rat and the mouse and in streptozotocin-induced diabetic mechanical allodynia.

Abstract
Somatostatin released from capsaicin-sensitive sensory nerves exerts systemic anti-inflammatory and antinociceptive actions. TT-232 is a stable, peripherally acting heptapeptide (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) somatostatin analogue with highest binding affinity for somatostatin sst4 receptors. It has been shown to inhibit acute and chronic inflammatory responses and sensory neuropeptide release from capsaicin-sensitive nociceptors. In the present study the antinociceptive effects of TT-232 were analysed using both acute and chronic models of nociception. Formalin-induced pain behaviour, noxious heat threshold and streptozotocin-induced diabetic neuropathic mechanical allodynia were examined in rats and phenylquinone-evoked abdominal constrictions were tested in mice. TT-232 (80 microg/kg i.p.) inhibited both early (0-5 min) and late phases (25-45 min) of formalin-induced nociception as revealed by determination of the composite pain score. The minimum effective dose to elevate the noxious heat threshold and diminish the heat threshold drop (heat allodynia) evoked by resiniferatoxin (0.05 nmol intraplantarly) was 20 and 10 microg/kg i.p., respectively, as measured by an increasing-temperature hot plate. TT-232 (10-200 microg/kg s.c.) significantly inhibited phenylquinone-evoked writhing movements in mice, but within this dose range no clear dose-response correlation was found. Five weeks after streptozotocin administration (50 mg/kg i.v.) the diabetes-induced decrease in the mechanonociceptive threshold was inhibited by 10-100 microg/kg i.p. TT-232. These findings show that TT-232 potently inhibits acute chemical somatic/visceral and thermal nociception and diminishes chronic mechanical allodynia associated with diabetic neuropathy, thereby it could open new perspectives in the treatment of various pain syndromes.
AuthorsJános Szolcsányi, Kata Bölcskei, Arpád Szabó, Erika Pintér, Gábor Petho, Krisztián Elekes, Rita Börzsei, Róbert Almási, Tamás Szuts, György Kéri, Zsuzsanna Helyes
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 498 Issue 1-3 Pg. 103-9 (Sep 13 2004) ISSN: 0014-2999 [Print] Netherlands
PMID15363982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics
  • Benzoquinones
  • Diterpenes
  • Peptides, Cyclic
  • Formaldehyde
  • phenylbenzoquinone
  • TT2-32
  • Somatostatin
  • resiniferatoxin
Topics
  • Acute Disease
  • Analgesics (pharmacology)
  • Animals
  • Behavior, Animal (drug effects)
  • Benzoquinones (toxicity)
  • Diabetes Mellitus, Experimental (complications)
  • Disease Models, Animal
  • Diterpenes (toxicity)
  • Dose-Response Relationship, Drug
  • Female
  • Formaldehyde (toxicity)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pain (chemically induced, etiology, prevention & control)
  • Pain Measurement (methods)
  • Peptides, Cyclic (pharmacology)
  • Rats
  • Rats, Wistar
  • Somatostatin (analogs & derivatives)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: