The brainstem’s parabrachial nucleus

I often reread blog posts that you read. Yesterday, a reader clicked Treat your gut microbiota as one of your organs. On rereading, I saw that I didn’t properly reference the parabrachial nucleus as being part of the brainstem.

A “parabrachial nucleus” search led me to a discussion of two 2020 rodent studies:

“Nociceptive signals entering the brain via the spinothalamic pathway allow us to detect location and intensity of a painful sensation. But, at least as importantly, nociceptive inputs also reach other brain regions that give pain its emotional texture.

Key to that circuitry is the parabrachial nucleus (PBN), a tiny cluster of cells in the brainstem associated with homeostatic regulation of things like temperature and food intake, response to aversive stimuli, and perceptions of many kinds. Two new papers advance understanding of PBN’s role in pain:

The PBN receives inhibitory inputs from GABAergic neurons in the central nucleus of the amygdala (CeA). Those inputs are diminished in chronic pain conditions, leading to PBN hyperactivity and increased pain perception. Disinhibition of the amygdalo-parabrachial pathway may be crucial to establishing chronic pain.

The dorsal PBN is the first receiver of spinal nociceptive input. It transmits certain inputs to the ventral medial hypothalamus and lateral periaqueductal gray. Certain of its neurons transmit noxious inputs to the external lateral PBN, which then transmits those inputs to the CeA and bed nucleus of the stria terminalis. This is quite new, that nociceptive information the CeA receives has already been processed by the PBN. They measured many pain-related behaviors: place aversion, avoidance, and escape. That allowed them to dissect different pain-related behaviors in relation to distinct subnuclei of the PBN.

Chronic pain is manufactured by the brain. It’s not a one-way process driven by something coming up from the periphery. The brain is actively constructing a chronic pain state in part by this recurring circuit.

A role of the PBN is to sound an alarm when an organism is in danger, but its roles go further. It is a key homeostatic center, weighing short-term versus long-term survival. If you’re warm, fed, and comfortable, organisms can address long-term directives like procreation. When you’re unsafe, though, you need to put those things off and deal with the emergency.”

https://www.painresearchforum.org/news/147704-parabrachial-nucleus-takes-pain-limelight “The Parabrachial Nucleus Takes the Pain Limelight”

https://www.jneurosci.org/content/40/17/3424 “An Amygdalo-Parabrachial Pathway Regulates Pain Perception and Chronic Pain”

https://www.sciencedirect.com/science/article/pii/S089662732030221X “Divergent Neural Pathways Emanating from the Lateral Parabrachial Nucleus Mediate Distinct Components of the Pain Response”

Two dozen papers have since cited these two studies. One that caught my eye was a 2021 rodent study:

“Migraines cause significant disability and contribute heavily to healthcare costs. Irritation of the meninges’ outermost layer (the dura mater), and trigeminal ganglion activation contribute to migraine initiation.

Dura manipulation in humans during neurosurgery is often painful, and dura irritation is considered an initiating factor in migraine. In rodents, dura irritation models migraine-like symptoms.

Maladaptive changes in central pain-processing regions are also important in maintaining pain. The parabrachial complex (PB) receives diverse sensory information, including a direct input from the trigeminal ganglion.

PB-projecting trigeminal ganglion neurons project also to the dura. These neurons represent a direct pathway between the dura, a structure implicated in migraine, and PB, a key node in chronic pain and aversion.”

https://www.sciencedirect.com/science/article/pii/S2452073X21000015 “Parabrachial complex processes dura inputs through a direct trigeminal ganglion-to-parabrachial connection”