Chronic Constriction Injury of the Distal Infraorbital Nerve (DIoN-CCI) in Mice to Study Trigeminal Neuropathic Pain.

Animal models remain necessary tools to study neuropathic pain. This manuscript describes the distal infraorbital nerve chronic constriction injury (DIoN-CCI) model to study trigeminal neuropathic pain in mice. This includes the surgical procedures to perform the chronic constriction injury and the postoperative behavioral tests to evaluate the changes in spontaneous and evoked behavior that are signs of ongoing pain and mechanical allodynia. The methods and behavioral readouts are similar to the infraorbital nerve chronic constriction injury (IoN-CCI) model in rats. However, important changes are necessary for the adaptation of the IoN-CCI model to mice. First, the intra-orbital approach is replaced by a more rostral approach with an incision between the eye and the whisker pad. The IoN is thus ligated distally outside the orbital cavity. Secondly, due to the higher locomotor activity in mice, allowing rats to move freely in small cages is replaced by placing mice in custom-designed and constructed restraining devices. After DIoN ligation, mice exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are similar to those in IoN-CCI rats, i.e., increased directed face grooming and hyperresponsiveness to von Frey hair stimulation of the IoN territory.

Effects of the combined continuous administration of morphine and the high-efficacy 5-HT1A agonist, F 13640 in a rat model of trigeminal neuropathic pain.

F 13640 is a recently discovered high-efficacy 5-HT1A receptor agonist that has demonstrated robust anti-allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5-HT1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5-HT1A receptor activation, and that the anti-allodynic effect that remained by the end of the two-week treatment period is due solely to 5-HT1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640.

Comparison between two types of behavioral variables of non-evoked facial pain after chronic constriction injury to the rat infraorbital nerve.

BACKGROUND AND PURPOSE: Chronic constriction injury to the rat infraorbital nerve (IoN-CCI) was reported to induce asymmetric face grooming directed to the territory of the injured nerve, and localized mechanical allodynia. The model has been used for pharmacologic testing; responsiveness to mechanical stimulation has been used as outcome measure, but face grooming behavior was not studied in this context. METHODS: Face grooming data from a series of four experiments using the IoN-CCI model were retrospectively analyzed, and two types of face grooming were identified: on the one hand, isolated face grooming (i.e., face grooming that is neither preceded nor followed by body grooming); and on the other hand, face grooming during body grooming (i.e., face grooming that is part of more general body grooming behavior). RESULTS: In all four experiments, amount of isolated face grooming was found to be significantly increased after IoN-CCI. In contrast, the amount of face grooming during body grooming was not significantly altered after IoN-CCI in any of the four experiments. CONCLUSIONS: The amount of isolated face grooming is a more sensitive outcome measure of neuropathic pain than is the total amount of face grooming, which includes face grooming during body grooming.