Pain signals converge in the core of the brainstem where they deeply influence behavior. For checks & balances, the brainstem uses “descending inhibition” as a volume control to reduce pain. Pain physicians leverage this for treatment, via antidepressants, acupuncture, & meditation.
Descending inhibition systems
To keep pain signals from running out of control, the brainstem has 3 checks & balances to dial down the intensity of pain signals directly at the spinal cord:
- LC (Locus coeruleus) uses norepinephrine to act on a2AR receptors in the spinal cord to reduce pain signal.
- RVM (Rostroventral medulla) uses serotonin to act on 5-HT receptors in the spinal cord. In the RVM, ON-cells increase pain signal & OFF-cells reduce it. Cannabinoids (marijuna) help reduce pain by activating OFF cells.
- PAG (Peri-aqueductal gray) is the central core of the brainstem which integrates emotional & autonomic inputs, & coordinates descending inhibition systems. It also responds to opioids and can drive addictive behavior.
Activating descending inhibition
The brainstem checks & balances systems can be medically activated to reduce pain intensity before the signal reaches the brain:
- Clonidine activates α2AR receptors
- Antidepressants activate serotonin and norepinephrine pathways. SNRIs include duloxetine, venlafaxine, & milnacipran. Tricyclic antidepressants include nortriptyline, desipramine
Pain physician & PhD computational biologist @StanfordPain • Advanced pain interventions with CIPS & FIPP • Opinions mine & not medical advice