naa a22 4500 510744176 CHVBK 20180411083039.0 cr unu---uuuuu 180411e20130801xx s 000 0 eng 10.1007/s12630-013-9975-x doi (NATIONALLICENCE)springer-10.1007/s12630-013-9975-x Evaluation of a novel mouse model of intracisternal strychnine-induced trigeminal allodynia [Elektronische Daten] [Il-Ok Lee, Ryan Whitehead, Craig Ries, Stephan Schwarz, Ernest Puil, Bernard MacLeod] Évaluation d'un modèle de souris innovant de l'allodynie du trijumeau induite par la strychnine administrée par voie intracisternale Purpose: Intractable neuropathic dynamic allodynia remains one of the major symptoms of human trigeminal neuropathy and is commonly accepted to be the most excruciatingly painful condition known to humankind. At present, a validated animal model of this disorder is necessary for efficient and effective development of novel drug treatments. Intracisternal strychnine in rats has been shown to result in localized trigeminal dynamic allodynia, thus representing a possible model of trigeminal neuralgia. The purpose of this study was to validate a mouse model of trigeminal glycinergic inhibitory dysfunction using established positive (carbamazepine epoxide) and negative (morphine) controls. Methods: The actions of conventional first-line treatment (carbamazepine epoxide [CBZe]) and clinically ineffective morphine were tested for trigeminal dynamic mechanical allodynia produced by intracisternal strychnine. In mice under halothane anesthesia, we injected either strychnine (0.3μg), strychnine with CBZe (4ng), or artificial cerebrospinal fluid (aCSF) intracisternally (i.c.). In a separate set of experiments, subcutaneous morphine (3mg·kg−1 sc) was injected with intracisternal strychnine. Dynamic mechanical allodynia was induced by stroking the fur with polyethylene (PE-10) tubing. The response of each mouse was rated to determine its allodynia score, and scores of each group were compared. In addition, in a separate dichotomous disequilibrium study, pairs of mice were injected with strychnine/saline, strychnine/strychnine-CBZe, or strychnine/strychnine-morphine. A blinded observer recorded which mouse of each pair had the greater global pain behaviour. Results: Strychnine (i.c.) produced higher quantitative allodynia scores in the trigeminal distribution (mean 81.5%; 95% confidence interval [CI] 76.4 to 86.6) vs the aCSF group (mean 11.3%; 95% CI 8.1 to 14.4) (P<0.0001). Carbamazepine epoxide (i.c.) completely abolished allodynia when co-injected with strychnine (mean 83.2%; 95% CI 78.1 to 88.4) vs strychnine alone (mean 3.2%; 95% CI −0.9 to 7.2) (P<0.0001). Morphine co-injected with strychnine did not result in reduced allodynia (mean 65.7%; 95% CI 42.0 to 89.4) compared with strychnine alone (mean 87.6%; 95% CI 77.6 to 97.6) (P=0.16). In a further global allodynia assessment, strychnine (i.c.) produced greater allodynia than both aCSF and strychnine administered with CBZe (P=0.03). Morphine (ip) administered with strychnine did not result in reduced global allodynia compared with strychnine administered alone (P=1.0). Conclusion: In this study, we have developed and validated a novel murine model of trigeminal dynamic allodynia induced by intracisternal strychnine. The use of mice to study trigeminal allodynia has many benefits, including access to a vast repository of transgenic mouse variants, ease of handling, low cost, and minimal variance of results. The present model may have utility in screening drug treatments for dynamic mechanical allodynia resulting from trigeminal neuropathies. Canadian Anesthesiologists' Society, 2013 Lee Il-Ok Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Korea aut Whitehead Ryan Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut Ries Craig Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut Schwarz Stephan Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut Puil Ernest Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut MacLeod Bernard Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut Canadian Journal of Anesthesia/Journal canadien d'anesthésie Springer US; http://www.springer-ny.com 60/8(2013-08-01), 780-786 0832-610X 60:8<780 2013 60 12630 https://doi.org/10.1007/s12630-013-9975-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12630-013-9975-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Il-Ok Department of Anesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Korea aut NATIONALLICENCE 700 1- Whitehead Ryan Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Ries Craig Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Schwarz Stephan Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Puil Ernest Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- MacLeod Bernard Hugill Anesthesia Research Centre, Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 773 0- Canadian Journal of Anesthesia/Journal canadien d'anesthésie Springer US; http://www.springer-ny.com 60/8(2013-08-01), 780-786 0832-610X 60:8<780 2013 60 12630 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer