Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse.

OBJECTIVES: To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. BACKGROUND: Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. METHODS: C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors. RESULTS: We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours. CONCLUSIONS: These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition.

A Comparison of Trabeculectomy Surgery Outcomes With Mitomycin-C Applied by Intra-Tenon Injection Versus Sponge.

PURPOSE: To compare the outcomes of mitomycin-C (MMC) delivered by intra-Tenon injection vs sponge application during trabeculectomy surgery. METHODS: We retrospectively reviewed 566 patients with primary and secondary glaucoma diagnoses who received trabeculectomy surgery with MMC in an academic medical center. Exclusion criteria were age less than 18 years, no light perception vision, combined surgery, previous glaucoma incisional surgery, intraoperative 5-fluorouracil, or follow-up <1 month. Subjects were divided into 2 cohorts: MMC delivered by sponge application or by intra-Tenon injection. Main outcome measures were postoperative intraocular pressure (IOP) level and secondary measures were survival rate for IOP control, glaucoma medication use, complication rate, and vision. RESULTS: After inclusion/exclusion criteria, 316 eyes were available for analysis; 131 eyes had MMC delivered via sponge and 185 eyes via injection. Mean postoperative IOP was not significantly different between treatment groups but change in IOP from baseline was lower in the sponge vs the injection group 24 months after surgery (P = .038). The MMC sponge group had significantly more tense, vascularized, or encapsulated blebs as a late complication (P = .046). Time to failure for postoperative IOP control was not significantly different between MMC treatment groups, but older patient age and limbus-based conjunctival incision were associated with significantly longer time to fail. CONCLUSIONS: The application of MMC by injection was similar to application by sponge in lowering IOP in patients with glaucoma and the safety of both techniques appears to be comparable. Limbus-based conjunctival incision had longer time to failure for postoperative IOP control vs fornix-based incision. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.