Abstract | OBJECTIVE: METHODS:
Triptans were administered systemically to rats by repeated intermittent injections or by continuous infusion over 6 days. Periorbital and hind paw sensory thresholds were measured to detect cutaneous allodynia. Immunofluorescent histochemistry was employed to detect changes in peptidic neurotransmitter expression in identified dural afferents. Enzyme-linked immunoabsorbent assay was used to measure calcitonin gene-related peptide (CGRP) levels in blood. RESULTS: Sustained or repeated administration of triptans to rats elicited time-dependent and reversible cutaneous tactile allodynia that was maintained throughout and transiently after drug delivery. Triptan administration increased labeling for CGRP in identified trigeminal dural afferents that persisted long after discontinuation of triptan exposure. Two weeks after triptan exposure, when sensory thresholds returned to baseline levels, rats showed enhanced cutaneous allodynia and increased CGRP in the blood following challenge with a nitric oxide donor. Triptan treatment thus induces a state of latent sensitization characterized by persistent pronociceptive neural adaptations in dural afferents and enhanced responses to an established trigger of migraine headache in humans. INTERPRETATION:
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Authors | Milena De Felice, Michael H Ossipov, Ruizhong Wang, Josephine Lai, Juliana Chichorro, Ian Meng, David W Dodick, Todd W Vanderah, Gregory Dussor, Frank Porreca |
Journal | Annals of neurology
(Ann Neurol)
Vol. 67
Issue 3
Pg. 325-37
(Mar 2010)
ISSN: 1531-8249 [Electronic] United States |
PMID | 20373344
(Publication Type: Journal Article)
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Chemical References |
- Nitric Oxide Donors
- Tryptamines
- Calcitonin Gene-Related Peptide
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Topics |
- Animals
- Calcitonin Gene-Related Peptide
(analysis, blood)
- Drug Administration Schedule
- Dura Mater
(physiopathology)
- Enzyme-Linked Immunosorbent Assay
- Fluorescent Antibody Technique
- Headache Disorders, Secondary
(physiopathology)
- Hyperalgesia
(chemically induced, physiopathology)
- Male
- Migraine Disorders
(drug therapy)
- Nitric Oxide Donors
(pharmacology)
- Nociceptors
(drug effects, physiology)
- Pain Measurement
- Pain Threshold
(drug effects, physiology)
- Rats
- Rats, Sprague-Dawley
- Reaction Time
(drug effects, physiology)
- Sensory Receptor Cells
(drug effects, physiology)
- Time Factors
- Trigeminal Nerve
(drug effects, physiopathology)
- Tryptamines
(adverse effects, toxicity)
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