The journey to understand chronic pain has been complex, and a dimension of this complexity is the marked differences in the prevalence and severity of chronic pain across sexes. In this illuminating episode, we sit down with Dr. Hildebrand, whose groundbreaking research explores the underpinnings of this phenomenon.

Dr. Hildebrand's work in Freund’s adjuvant in vivo model of inflammatory pain identified a pathological coupling between KCC2-dependent disinhibition and NMDA receptor (NMDAR) potentiation within superficial dorsal horn neurons in male rats - but not in females. The study further showed that brain-derived neurotrophic factor (BDNF), a key neuroimmune mediator, did not regulate the same inhibitory and excitatory signaling elements in females as it did in males.

Remarkably, this sex-specific difference in spinal pain proces ...