Neuroprotective Effect of Enriched Chicken Bone Broth as a Dietary Supplement in a Model of Migraine Mediated by Early Life Stress

Early life stress is a risk factor for development of migraine, a prevalent painful neurological disease characterized by sensitization and activation of trigeminal neurons. Secondary early life stress was previously shown to cause increased expression of neuronal proteins implicated in peripheral and central sensitization. Recently, dietary supplementation of chicken bone broth was shown to attenuate trigeminal nociception in an orofacial pain model. Accordingly, the focus of this study was to determine the effects of early life stress and dietary inclusion of bone broth on trigeminal nociceptor sensitization and activation in a model of episodic migraine. Adult Sprague-Dawley male sender rats subjected to primary traumatic stress were placed next to breeding or pregnant female rats that served as receiver rats (secondary traumatic stress) and in proximity to the offspring until weaning. Unstressed and stressed young adult offspring were tested for mechanical nocifensive response after exposure to a pungent odor known to be a migraine trigger, and in response to daily supplementation of bone broth. Early life stress promoted a primed state of trigeminal nociceptors that were activated by the pungent odor in both genders. Female animals exhibited a higher basal sensitization level and prolonged nociception compared with males. Supplementation of bone broth beginning at the time of weaning inhibited basal and triggered trigeminal mechanical sensitivity. Early life stress caused development of a sensitized trigeminal system that is implicated in migraine pathology and dietary supplementation with bone broth suppressed trigeminal sensitization, and thus may provide neuroprotective activity for reducing migraine risk.