Tactile-induced ultrasonic vocalization in the rat: a novel assay to assess anti-migraine therapies in vivo.
A pharmacological model of migraine is described using ultrasound vocalization (USV) of rats following central inflammation-induced sensitization to tactile stimulation. Central inflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS) increased USV induced by an air current focused on the head and this was abolished by morphine and ketorolac, suggesting a nociceptive component. USV in naive rats were unaffected. Diazepam reduced USV in both inflamed and naive rats. The triptans, zolmitriptan and sumatriptan, both reduced USV in inflamed but not in naive rats, as did dihydroergotamine, and the calcitonin gene-related peptide (CGRP) antagonists alphaCGRP(8-37) and BIBN4096BS. The neurokinin-1 antagonist L-733-060 had no effect in either inflamed or naive rats when given after induction of inflammation, but when given with the LPS it prevented the augmentation of USV. This profile of activity of agents proven to be effective in the clinic suggests this model can be used to predict novel therapeutic agents for migraine.
Martino
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AstraZeneca Research and Development Montreal, Ville St Laurent, Montreal, Quebec, Canada. john.martino@astrazeneca.com
Perkins
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MN
D000284:Administration, Oral; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D020910:Ketorolac / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008581:Meningitis / Q000139:chemically induced / Q000503:physiopathology*; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009020:Morphine / Q000627:therapeutic use; D009619:Nociceptors / Q000187:drug effects* / Q000503:physiopathology; D023303:Oxazolidinones / Q000627:therapeutic use; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014110:Touch / Q000187:drug effects* / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000503:physiopathology*; D014363:Tryptamines / Q000627:therapeutic use; D014828:Vocalization, Animal / Q000187:drug effects*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015507:Drugs, Investigational; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D023303:Oxazolidinones; D014363:Tryptamines; C089750:zolmitriptan; D009020:Morphine; D003975:Diazepam; D020910:Ketorolac