TY - JOUR
T1 - A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain
AU - Munro, Gordon
AU - Petersen, Steffen
AU - Jansen-Olesen, Inger
AU - Olesen, Jes
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological changes occurring within dural or trigeminal pain circuits. We generated successive generations of a unique inbred rat strain, spontaneous trigeminal allodynia (STA) rats, previously reported to exhibit an episodic migraine-like behavioural phenotype. We show that both male and female STA rats display robust and sustained reductions in periorbital thresholds to cutaneous mechanical stimulation. Otherwise, the general behavior (e.g. locomotor, grooming) of these rats appeared normal. In female STA rats, the mechanical hypersensitivity was confined to the cephalic region, manifested after puberty through adolescence, and was sustained into adulthood recapitulating the clinical manifestation of migraine. We exploited this hitherto unidentified chronic phenotype to show that the migraine-specific drugs sumatriptan (5-HT1B/1D receptor agonist) and olcegepant (CGRP receptor antagonist) could completely reverse cephalic hypersensitivity using a within subject cross-over paradigm. Our findings indicate that STA rats actually possess a phenotype indicative of migraine chronicity which is exquisitely sensitive to migraine therapeutics. This unique strain could prove to be an invaluable resource in preclinical migraine drug discovery.
AB - Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological changes occurring within dural or trigeminal pain circuits. We generated successive generations of a unique inbred rat strain, spontaneous trigeminal allodynia (STA) rats, previously reported to exhibit an episodic migraine-like behavioural phenotype. We show that both male and female STA rats display robust and sustained reductions in periorbital thresholds to cutaneous mechanical stimulation. Otherwise, the general behavior (e.g. locomotor, grooming) of these rats appeared normal. In female STA rats, the mechanical hypersensitivity was confined to the cephalic region, manifested after puberty through adolescence, and was sustained into adulthood recapitulating the clinical manifestation of migraine. We exploited this hitherto unidentified chronic phenotype to show that the migraine-specific drugs sumatriptan (5-HT1B/1D receptor agonist) and olcegepant (CGRP receptor antagonist) could completely reverse cephalic hypersensitivity using a within subject cross-over paradigm. Our findings indicate that STA rats actually possess a phenotype indicative of migraine chronicity which is exquisitely sensitive to migraine therapeutics. This unique strain could prove to be an invaluable resource in preclinical migraine drug discovery.
KW - Animals
KW - Disease Models, Animal
KW - Drug Hypersensitivity/etiology
KW - Female
KW - Hyperalgesia/drug therapy
KW - Male
KW - Migraine Disorders/drug therapy
KW - Pain/drug therapy
KW - Rats
KW - Rats, Inbred Strains
KW - Rats, Sprague-Dawley
KW - Receptor, Serotonin, 5-HT1B/metabolism
KW - Serotonin 5-HT1 Receptor Agonists/pharmacology
KW - Trigeminal Nerve/drug effects
U2 - 10.1038/s41598-018-19901-1
DO - 10.1038/s41598-018-19901-1
M3 - Journal article
C2 - 29382888
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
M1 - 1836
ER -