Prolonged Trigeminal Sensitization Induces Gut Dysbiosis: Implications for Migraine Pathology (S51.006)

Objective: To investigate the effects of prolonged trigeminal neuron sensitization on the composition of the gut microbiota. Background: Migraine is characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Clinically, neck muscle pathology and sleep deprivation are reported as co-morbid conditions by migraine patients. Another pathological condition associated with more frequent migraine is irritable bowel syndrome (IBS). A communication link between the gut microbiota and brain is well established. Since an imbalance in gut microbiota (dysbiosis) is implicated in pathological conditions, a better understanding of this relationship is essential for understanding migraine pathology. Methods: To promote prolonged sensitization of trigeminal neurons, adult male Sprague-Dawley rats were injected with complete Freund’s adjuvant (CFA) in the trapezius muscle and REM sleep deprived for one night. Nocifensive behavioral changes in response to mechanical stimulation in the orofacial region were determined using von Frey filaments. Fecal samples were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to visualize microbial populations in the gut microbiota. DNA sequencing was used to identify bacteria associated with major shifts in resident populations associated with healthy naive and sensitized animals. Results: The combination of neck muscle pathology and REM sleep deprivation caused sustained increases in trigeminal nocifensive behavior to mechanical stimulation. The development of prolonged trigeminal sensitization was associated with major shifts in the gut microbiota when compared to healthy naive animals. Sequence analysis revealed that shifts largely occurred in phyla implicated in intestinal and organismal health. Prolonged sensitization resulted in a loss of commensal bacteria and the emergence of bacteria not abundantly seen in healthy animals. Conclusion: Our results provide evidence that prolonged sensitization of trigeminal neurons promotes development of dysbiosis, which may help to explain why IBS is often reported as a co-morbid condition as the frequency of migraine increases. Study Supported by: NIH DE017805. Disclosure: Dr. Hawkins has nothing to disclose. Dr. Norton has nothing to disclose. Dr. Norton has nothing to disclose.