Abstract
BackgroundTrigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.ResultsThe chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70). Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks.ConclusionsA simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2) is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.
Highlights
Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched
Infraorbital nerve gross anatomy and histology Anatomical, histological and behavioral confirmation was sought that the chromic gut suture placed between the infraorbital nerve and the maxillary bone was the source of whisker pad hypersensitivity, and that mice in the sham group did not develop hypersensitivity after only surgical exposure of the infraorbital nerve (Figure 1A-D)
Inflammatory immunoreactivity in trigeminal ganglia neurons and spinal trigeminal nucleus The present results indicate that the chromic gut suture caused partial nerve compression and the toxic chemicals released locally produced irritation and mild inflammatory response in our mouse model sufficient to produce continuous mechanical allodynia for at least 10 weeks
Summary
Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Using two loose chromic gut suture ligatures applied to the infraorbital branch of the trigeminal nerve to promote orofacial hypersensitivity, Vos et al [2] first adapted the widely used method referred to as the chronic constriction injury (CCI) model by Bennett and Xie [3] which is typically applied to the sciatic nerve in rats. Since that time several models have been developed for rodents using the inferior alveolar, mental, or the infraorbital as target nerves for injury models in orofacial pain studies. These nerves and their whisker pad receptive field testing areas are of much smaller size in mice compared to rats. The method reported here provides a stable orofacial neuropathic pain model which better mimics clinical chronic orofacial neuropathic pain
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