Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors

Abstract

Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week 8 post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury which resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model’s chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.

Neuropathic pain drives anxiety behavior in mice, results consistent with anxiety levels in diabetic neuropathy patients

“…Again, published data in this area are contradictory, with some showing no association between nerve injury and anxiety behavior, 17 , 40 whereas others show that neuropathic injury increases anxiety-like behavior. 9 , 23 , 25 , 38 , 45 Interestingly, our findings combined with these other studies suggest a time sensitivity to these events. Within the first few weeks after nerve injury, affective state was relatively unaffected, 17 , 40 but with neuropathic pain for more than 4 weeks after injury, anxiety-like behavior becomes apparent.…”

Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons

“…In this study, IoN-CCI led to significant changes in responses evoked by mechanical stimulation of the face. Additionally, consistent with previously reports that tissue or nerve injury could induce anxiety/depression-like behaviors in rodents ( Dai et al, 2011 ; Lyons et al, 2015 ), our results also demonstrated that IoN-CCI could produce pain-related negative emotional behaviors such as anxiety/depression, as revealed by the OF and EPM tests.…”

Peripheral and Central Neuroinflammatory Changes and Pain Behaviors in an Animal Model of Multiple Sclerosis

“…Testing of mechanical pain hypersensitivity in the hind paws was terminated at disease peak due to paralysis. The restrictions imposed by hind limb motor confounds on continual testing of mechanical allodynia in clinical EAE prompted us to use a technique developed for testing mechanical pain in the face ( 19 ), which is not affected by motor deficits. We found that EAE mice were significantly more responsive to mechanical stimuli applied to the whisker pad than control mice over the entire course of chronic EAE, as seen on days 6, 8, 10, 17, and 30 (Figure 1 D, n = 4–9, p < 0.05–0.001).…”

“…Facial allodynia was assessed using a method previously described by Lyons et al to measure facial pain in a model of trigeminal inflammatory compression injury ( 19 ). In the week prior to baseline behavioral testing, animals were handled daily using a cotton glove in order to gradually acclimatize the mice to being gently restrained in the experimenter’s hand.…”