How to activate the brain to treat pain?

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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:

  1. LC (Locus coeruleus) uses norepinephrine to act on a2AR receptors in the spinal cord to reduce pain signal.
  2. 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.
  3. 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
  • Acupuncture
  • Meditation