Partial infraorbital nerve ligation as a model of trigeminal nerve injury in the mouse: behavioral, neural, and glial reactions.
Trigeminal nerve damage often leads to chronic pain syndromes including trigeminal neuralgia, a severely debilitating chronic orofacial pain syndrome. Options for treatment of neuropathic pain are limited in effectiveness and new approaches based on a better understanding of the underlying pathologies are required. Partial ligation has been shown to effectively mimic many of the qualities of human neuropathic pain syndromes. We have devised a mouse model of trigeminal neuralgia using a partial infraorbital nerve ligation (pIONL) that induces persistent pain behaviors and morphological changes in the brainstem. We found that the pIONL effectively induced mechanical allodynia lasting for more than 3 weeks. Cell proliferation (bromodeoxyuridine), activation of astrocytes and microglia in the ipsilateral caudal medulla, and persistent satellite cell reaction in the ipsilateral ganglion were observed. Neurochemical markers calcitonin gene-related peptide, substance P were decreased in medullary dorsal horn ipsilateral to the injury side, whereas substance P receptor NK1 expression was increased after 8 days. Nerve injury marker ATF3 was markedly increased in ipsilateral trigeminal ganglion neurons at 8 days after pIONL. The data indicate that partial trigeminal injury in mice produces many persistent anatomical changes in neuropathic pain, as well as mechanical allodynia.


CONCLUSIONS
This study describes the development of a new mouse model of trigeminal neuropathic pain. Our goal is to devise better treatments of trigeminal pain, and this will be facilitated by characterization of the underlying cellular and molecular neuropathological mechanisms in genetically designed mice.
Xu
Mei
M
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA. xum@u.washington.edu
Aita
Megumi
M
Chavkin
Charles
C
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020220:Facial Nerve Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006120:Grooming / Q000502:physiology; D007150:Immunohistochemistry; D008026:Ligation / Q000379:methods; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D027161:Satellite Cells, Perineuronal / Q000378:metabolism / Q000473:pathology; D013373:Substance P / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000473:pathology; D061221:Trigeminal Nerve Injuries; D014277:Trigeminal Neuralgia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D018040:Receptors, Neurokinin-1; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide