Trigeminal Neuralgia Induced by Cobra Venom in the Rat Leads to Deficits in Abilities of Spatial Learning and Memory

Background: Patients with chronic pain usually suffer from cognitive impairment, with memorydeterioration being the most common deficit that affects daily functioning and quality of life. Thecauses for this impairment are not clear despite intensive clinical studies. Few studies have evaluatedimpaired learning using animal models of persistent pain.Objective: In this study, a new trigeminal neuralgia model induced by cobra venom was adoptedto explore effects of chronic pain on spatial learning and memory in rats.Study Design: Controlled animal study.Setting: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation GeneralHospital of China Medical University.Methods: Thirty adult male Sprague-Dawley rats were randomly divided into 2 groups (n = 15): NScontrol group and cobra venom group, 0.9% sterile saline or cobra venom solution was injected intothe sheath of the infraorbital nerve (ION), respectively. The development of trigeminal neuralgia wasaccessed by changes in free behavioral activity 3 days before the surgery and 3, 7, 12, 20, and 30days after the surgery to identify whether the model was successful or not. Morris water maze testdetermined the abilities of spatial learning and memory at the time points before the surgery, and2 weeks and 5 weeks after the surgery. We also observed the ultrastructure of the ION and medullaoblongata of rats following 8 weeks of chronic trigeminal neuropathic pain.Results: Rats with the cobra venom injection displayed significantly more face grooming and fewerexploratory activities compared to the NS control group or baseline (P < 0.01). Both groups improvedtheir latency to reach the platform with the largest difference on the first day (P < 0.01), but withoutmemory deficits in a probe trial for the second water maze protocol. For the third water maze testing,the rats in the cobra venom group experienced decreased abilities of spatial learning and memory,a longer latency with spatial memory deficits during the probe trial (P < 0.05). At the ultrastructurallevel, we found changes in the medulla oblongata after cobra venom injection resulting in severedemyelination and loss of axons that might be implicated in the causes of cognitive deficits.Limitations: Limitations include partial vision loss in the eye on the lesion side of the rats thatmight be missed and the absence of evaluating the ultrastructural changes in other parts of thebrain.Conclusions: The results of this study suggest that trigeminal neuralgia induced by cobra venomin adult rats can impair spatial learning and memory function over time and results in demonstrablechanges in the ultrastructure of the medulla oblongata. This new animal model may be useful forfuture studies on the effect of chronic pain on learning and cognition.Key words: Cognitive deficits, memory deterioration, cobra venom, trigeminal neuralgia, electronmicroscopy