Orofacial pain models induce impairment in spatial learning and working memory in rodents: A systematic review and meta-analysis

Orofacial pain is one of the most common causes of chronic pain leading to physical and cognitive disability. Several clinical and pre-clinical studies suggest that chronic pain results in cognitive impairment. However, there is a lack of meta-analyses examining the effects of orofacial pain models on behavioral learning and memory in rodents. Thus, this study aimed to evaluate whether orofacial pain models can impair learning and memory in rodents. The protocol was registered in PROSPERO (CRD42023355502). We used CAMARADES and SYRCLE to estimate the quality and the publication bias by using Egger's and Begg's test. Here, 21 studies were included in this systematic review and meta-analysis. We included 12 studies with trigeminal neuralgia models, 4 with migraine-like pain models, 4 with tooth nociception, and 1 with acute orofacial pain model. Spontaneous nociception and facial mechanical allodynia were observed in orofacial pain models. Regarding spatial learning we detected that latency to find the platform in the Morris water maze (MWM) was increased in orofacial pain models (related to facial mechanical allodynia or spontaneous nociception). Although the mean quality of the articles was high, we identify publication bias in the Begg's test for the time in the quadrant in the MWM. Our findings revealed that spontaneous nociception and facial mechanical allodynia in orofacial pain models contribute to the working memory and spatial learning dysfunction. Therefore, further studies are still needed to evaluate the influence of sex, age, social isolation, and environmental enrichment in orofacial pain-related learning and memory.