Taking a deep breath: How a brainstem pathway integrates pain and breathing

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Respiratory Control

Background:

• Elevated breathing rhythms are common physiological responses to pain and anxiety.
• The precise neural circuits governing these respiratory changes remain incompletely understood.
• Opioid signaling plays a role in modulating stress and pain, but its specific circuit contributions to breathing are unclear.

Purpose of the Study:

• To elucidate the neural circuits underlying pain- and anxiety-induced alterations in breathing patterns.
• To investigate the role of specific neuronal populations expressing opioid receptor-1 (Oprm1) in regulating these behaviors.
• To differentiate the functions of distinct Oprm1-expressing neuronal populations in the context of stress and respiration.

Main Methods:

• Utilized advanced techniques in neuroanatomy and circuit tracing.
• Employed genetic manipulation to target specific neuronal populations.
• Recorded and analyzed respiratory rhythms in response to pain and anxiety stimuli.

Main Results:

• Identified distinct populations of Oprm1-expressing neurons in the parabrachial nucleus (PBL) core and the nucleus accumbens shell.
• Demonstrated that PBL core-Oprm1 neurons project to the central amygdala (CeA) and modulate anxiety-related breathing.
• Showed that shell-Oprm1 neurons project to the pre-Bötzinger complex (preBötC) and regulate pain-induced breathing changes.

Conclusions:

• PBL core-Oprm1 neurons and shell-Oprm1 neurons act as differential regulators of pain- and anxiety-induced breathing.
• This study reveals a novel circuit-level understanding of how stress impacts respiratory control.
• Findings provide insights into potential therapeutic targets for conditions involving aberrant breathing during pain and anxiety.