Distal infraorbital nerve injury: a model for persistent facial pain in mice

Abstract

Inflammation or injuries of the trigeminal nerve are often associated with persistent facial pain and its sequelae. A number of models have been described to study trigeminal pain in rodents, but the long-lasting behavioral consequences are unknown. This study characterizes the impact of a distal infraorbital nerve injury, called DIONI, which consists of ligature and transection of distal fibers of the infraorbital nerve. We assessed nociception using a conflict paradigm and optogenetics, and a set of reward, aversion, spatial, temporal, and competition tasks in the IntelliCage to study multiple aspects of cognition, circadian rhythms, and social interactions in groups of mice in home cage environments. Mice with DIONI developed cold and mechanical allodynia, and hypersensitivity towards blue light stimulation. They maintained a long-lasting memory of aversive stimuli (airpuff from above), but had no difficulty in learning appetitive tasks, which consisted in developing a preference for a rewarding corner in the IntelliCage. Indeed, they were more strongly “addicted” to sugar than sham mice but temporarily failed to relearn the location of rewarding sites after corner switching (reversal learning). They were mildly overactive in some tasks but without disruptions of circadian rhythms or impact on social structure. They adopted a strategy to maintain licking with fewer nosepokes, presumably trying to avoid mechanical stimulation of the snout. The results suggest that mice with DIONI develop strong aversive memories and some cognitive inflexibility, but create adaptive strategies to cope with the persistent trigeminal hypersensitivity.

Low brain endocannabinoids associated with persistent non-goal directed nighttime hyperactivity after traumatic brain injury in mice

“…In previous studies, we found that trigeminal nerve injury increased blue light avoidance 61 presumably owing to upregulations of melanopsin in injured nerves 62 , leading to blue light-triggered headache or migraine. However, in the present study in the Red/Blue box, both groups equally preferred the red light (Fig.…”

“…Assessment of blue light sensitivity in posttraumatic headache. Blue light sensitivity was assessed as described 61 . A plexiglass test chamber (25 × 10 × 15 cm) was divided into 3 zones, i.e.…”

“…The time schedule for the IntelliCage experiments is shown in Fig. 4, and the experiments followed protocols described in our previous studies 61,76,96,97 and were adapted to TBI mice. They are summarized in Table 1.…”

“…In the Place Avoidance Acquisition (PAA) task (as described e.g. in 61,97 , mice learnt to avoid one corner, where a nosepoke triggered a red LED and an air-puff (1 s; 0.8 bar) from above the head. The door remained closed so that water access was denied.…”

Sensory neuropathy and nociception in rodent models of Parkinson's disease

“…Mechanical nociception is assessed as withdrawal threshold upon stimulation with von Frey hairs (Table 2) or with a thin steel rod with ascending force (dynamic plantar test; Table 2), or upon squeezing the paw (Le Bars et al, 2001). In addition, specific tests were developed for assessing headache or orofacial pain, including observation of spontaneous face rubbing upon injection of nitroglycerin (Akerman et al, 2013; Ferrari et al, 2016; Greco et al, 2018) and assessment of conflict behavior in the orofacial pain assessment device (OPAD; Table 2) (Cha et al, 2012; Hardt et al, 2019). Further nociceptive models rely on spinal reflexes evoked by injection of either formalin into a hind paw or acetic acid into the peritoneal cavity, causing quantifiable paw licking/flicking or abdominal writhing (Le Bars et al, 2001).…”