Role of the Parabrachial Complex in Rodent Models of Pain

Abstract

The parabrachial complex (PB) is a midbrain structure that is vital to survival-related functions. This region receives and integrates incoming sensory information, communicating these signals to higher brain regions that are key in shaping behavior and affect. PB responds to painful somatosensory input, however, its most compelling role is in the development and maintenance of persistent pain. Pain persisting beyond the duration of a threat or tissue injury no longer serves a physiological purpose. Therefore, this type of maladaptive pain has a severe impact on health and quality of life. Current therapies for maladaptive pain are not optimal: it is necessary to better understand the neural circuitry underlying persistent pain so that we can design more effective therapies. The work presented here aims to outline PB’s role in four rodent models of pain. I approach this by combining anatomical tracing, electrophysiology, and behavioral studies. First, I show that in a model of orofacial neuropathic pain, PB neural activity is amplified. Next, I describe a novel and direct anatomical connection between the meninges and PB, via the trigeminal ganglion; this pathway is poised to underlie migraine headache-associated pain. Finally, I conduct behavioral studies aiming to hone rodent models of pain in the context of aging and amyloid accumulation, and pain during opioid withdrawal. These findings together confirm that PB is a crucial node in maladaptive pain processing and provide direction for further work clarifying PB’s role in new behavioral contexts.