Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators.
Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown. Here we tested if trigeminal nucleus caudalis (Sp5C) glial and/or immune cells are activated following supradural inflammatory soup, and if putative glial/immune inhibitors suppress the consequent facial allodynia. Inflammatory soup was administered via bilateral indwelling supradural catheters in freely moving rats, inducing robust and reliable facial allodynia. Gene expression for microglial/macrophage activation markers, interleukin-1β, and tumor necrosis factor-α increased following inflammatory soup along with robust expression of facial allodynia. This provided the basis for pursuing studies of the behavioral effects of 3 diverse immunomodulatory drugs on facial allodynia. Pretreatment with either of two compounds broadly used as putative glial/immune inhibitors (minocycline, ibudilast) prevented the development of facial allodynia, as did treatment after supradural inflammatory soup but prior to the expression of facial allodynia. Lastly, the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone likewise blocked development of facial allodynia after supradural inflammatory soup. Taken together, these exploratory data support that activated glia and/or immune cells may drive the development of facial allodynia in response to supradural inflammatory soup in unanesthetized male rats.
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Julie
J
Wieseler
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Amanda
A
Ellis
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Andrew
A
McFadden
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Kendra
K
Stone
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Kimberley
K
Brown
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Sara
S
Cady
Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, 6627, CEP 31270-901 Minas Gerais, Brazil.
Leandro F
LF
Bastos
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
David
D
Sprunger
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Niloofar
N
Rezvani
MediciNova Inc, 4350 La Jolla Village Dr., #950, San Diego, CA, USA.
Kirk
K
Johnson
Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Kenner C
KC
Rice
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Steven F
SF
Maier
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA. Electronic address: linda.watkins@colorado.edu.
Linda R
LR
Watkins
D000818:Animals; D004388:Dura Mater / Q000187:drug effects; D004660:Encephalitis / Q000150:complications / Q000276:immunology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D008881:Migraine Disorders / Q000150:complications; D008911:Minocycline / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000276:immunology*; D007212:Indolizines; D011720:Pyrazoles
D018836:Inflammation Mediators; D008911:Minocycline; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles
Dura; Headache; Interleukin-1; Migraine; OX42; Tumor necrosis factor alpha