When pain engages the brain Experimental orofacial pain: Behavioral, cognitive, and emotional consequences in preclinical models

The general aim of this thesis was to investigate the behavioral, cognitive, and emotional consequences of experimental orofacial pain and to examine how trigeminal nociception is influenced by stress, descending pain modulation, and behavioral interventions. Five preclinical studies in rats explored migraine-like and inflammatory dental pain using complementary experimental models.
The findings show that trigeminal pain is not merely a sensory event, but a multidimensional process involving emotional and cognitive functions. Early-life stress increased vulnerability to migraine-like behaviors in a sex-dependent manner, while chronic psychological and social stress amplified inflammatory dental pain. Blockade of cannabinoid type 1 receptors in the ventrolateral periaqueductal gray increased dental pulp pain and worsened pain-related learning and memory deficits, supporting a protective role for endogenous cannabinoid signaling. In contrast, regular physical exercise reduced pulpal pain and prevented associated impairments in learning and memory. Inflammatory tooth pain also induced anxiety-like behavior, further demonstrating the close interaction between nociception and affect.
Taken together, the studies indicate that trigeminal pain is shaped by vulnerability and resilience factors operating across nociceptive, cognitive, and emotional networks. Stress emerges as an important facilitator of pain, whereas intact descending cannabinoid signaling and exercise exert protective effects. These findings support a broader, network-based understanding of orofacial pain and provide a basis for future translational research aimed at improving prevention and treatment strategies.