The Role of Parabrachial in Nociception and Pain in Awake Mice

Abstract

The parabrachial nuclear complex is a nexus for aversion, and for the sensory and affective components of pain perception. It has been previously shown that, during chronic pain, parabrachial neurons have increased activity and respond to noxious stimuli with prolonged after-discharges – responses that far outlast the stimulus. This phenomenon—like most of what we know about the electrophysiology of pain—has only been observed in anesthetized animals. Anesthesia profoundly alters neuronal responses to nociceptive stimuli and masks their responses to the affective component of pain. I have developed a method to investigate parabrachial neurons in awake, behaving animals by recording single units in vivo from head restrained mice, and applying reproducible noxious stimuli. This offered opportunities to study the time course of changes in parabrachial activity by recording repeatedly from the same animals. It also allows me to correlate parabrachial activity with the animal's behavioral state, by using pupil changes as a proxy for internal states. I report that, in parabrachial neurons from both male and female mice, anesthesia leads to decreased activity, including a decrease in spontaneous activity and reduced magnitude of responses to noxious stimuli. I also demonstrate that, in awake mice, evoked response after chronic pain results in a lasting amplification of parabrachial activity. Finally, I show that changes in parabrachial activity are related to changes in arousal, measured as increases in pupil diameter states.