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

• Published in: European journal of pharmacology Vol. 498; no. 1; pp. 103 - 109
• Main Authors: Szolcsányi, János, Bölcskei, Kata, Szabó, Árpád, Pintér, Erika, Pethő, Gábor, Elekes, Krisztián, Börzsei, Rita, Almási, Róbert, Szűts, Tamás, Kéri, György, Helyes, Zsuzsanna
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.09.2004; Elsevier
• Subjects: Acute Disease; Analgesic effect; Analgesics - pharmacology; Animals; Behavior, Animal - drug effects; Benzoquinones - toxicity; Biological and medical sciences; Diabetes Mellitus, Experimental - complications; Diabetes. Impaired glucose tolerance; Diabetic neuropathy; Disease Models, Animal; Diterpenes - toxicity; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Formaldehyde - toxicity; Formalin test; Male; Medical sciences; Mice; Mice, Inbred BALB C; Pain - chemically induced; Pain - etiology; Pain - prevention & control; Pain Measurement - methods; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Somatostatin; Somatostatin - analogs & derivatives; Thermal nociception; Writhing test; Diabetic neuropathy; Thermal nociception; Somatostatin; Writhing test; Analgesic effect; Formalin test; Endocrinopathy; Antineoplastic agent; Animal model; Peptide hormone; Neuropathy; Neuropeptide; Pain; Streptozotocin; Allodynia; Nociception; Nervous system diseases; Diabetes mellitus; Rodentia; Vertebrata; Antibiotic; Mammalia; Analgesic; Mouse; Animal
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.07.085

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-NH 2) somatostatin analogue with highest binding affinity for somatostatin sst 4 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 μg/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 μg/kg i.p., respectively, as measured by an increasing-temperature hot plate. TT-232 (10–200 μg/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 μg/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.