Journal
PAIN
Volume 134, Issue 1-2, Pages 97-105Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2007.03.037
Keywords
neurogenic inflammation; plasma extravasation; vasodilation; substance P; CGRP; sumatriptan; 5-HT1B/D receptor agonists; nociceptor
Categories
Ask authors/readers for more resources
Activation of the 5-HT1B/D receptor inhibits cerebrovascular neurogenic inflammation (NI). The aim of this study was to determine if the 5-HT1B/D receptor agonist sumatriptan can also inhibit NI in other regions of the body. NI was assessed by measuring plasma extravasation (PE) and changes in blood flow in the rat hindpaw. Sumatriptan was administered locally (20 mu l, 50 or 100 nM, s.c.) into the dorso-medial region of one hindpaw. The other paw was pre-treated with vehicle (20 mu l of 0.9% saline) and served as a control. NI was induced after treatment with sumatriptan/vehicle by injecting capsaicin (15 mu l, 1%, s.c.) into each paw or by electrically stimulating the saphenous nerve (4 Hz, 30 s). Sumatriptan administered locally or systemically (300 mu g/kg, i.v.) significantly reduced saphenous nerve and capsaicin-induced PE and vasodilation. The systemic and local inhibitory actions of sumatriptan are mediated by the 5-HT1B/D receptor as pre-treatment with the 5-HT1B/D antagonist GR127935 (GR; 15 mu l, 1 mu M, s.c. or 0.2 mu mol/kg, i.v.) completely blocked the inhibitory effect of sumatriptan on capsaicin-induced vasodilation and reduced the inhibitory effect of sumatriptan on capsaicin and electrically induced-PE. Neither PE induced by local injection of substance P (SP) (20 pmol, 20 mu l, s.c.) nor vasodilation induced by local CGRP injection was affected by pre-treatment with sumatriptan. These findings indicate that both local and systemic activation of the 5-HT1B/D receptor by sumatriptan reduce NI induced by nerve stimulation or capsaicin presumably by inhibiting neuropeptide release. 5-HT1B/D receptor agonists may be useful for the treatment of non-trigeminal pain conditions involving NI. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available