Dr. Sean Mackey: Physician-scientist who is Chief of the Division of Pain Medicine and a professor of anesthesiology and neurology at Stanford. He runs a pain research lab, built a digital health platform for pain, and co-led the U.S. National Pain Strategy.
What this episode covers
Andrew Huberman and Dr. Sean Mackey take a broad, deep tour of pain: what it is, where it arises in the body and brain, and why it is a subjective sensory-and-emotional experience that differs for everyone. They cover over-the-counter and prescription drugs (NSAIDs, acetaminophen, opioids), mechanical and neuromodulatory tools (rubbing, TENS, heat and cold), and the psychological dimension including catastrophizing, anger, mindfulness, and the hurt-versus-harm distinction. Mackey shares personal stories (a food-triggered chronic abdominal pain, his own neck pain) and research, including a study showing romantic love reduces pain via reward circuitry. The conversation tackles the opioid crisis with nuance, plus kratom, cannabis, acupuncture, chiropractic, physical therapy, nutraceuticals, and his mission to disseminate free, high-quality pain care.
Also referenced (named, not recommended)
Naprosyn (naproxen)
Roche
“The two over-the-counter NSAIDs, the prototypical over-the-counter ones, are ibuprofen and Naprosyn. Those are the ones you can buy over the counter”— Sean Mackey
Toradol (ketorolac)
ketorolac
“Naproxen is another one. Toradol or ketorolac is another one. The two over-the-counter NSAIDs... are ibuprofen and Naprosyn”— Sean Mackey
Celecoxib (Celebrex)
Pfizer
“There are versions of the NSAIDs that we refer to as cox2 inhibitors. They're very selective, like celecoxib, that is less irritating on the stomach”— Sean Mackey
TENS device
transcutaneous electrical nerve stimulation
“there was the introduction of a device to take advantage of this called the tens device. And tens is an acronym. Transcutaneous electrical nerve stimulation”— Sean Mackey
MS Contin
Purdue Pharma
“Morphine and its commercial derivatives MS Contin, which is a long lasting version of morphine”— Sean Mackey
Tramadol
Grunenthal
“There are mixed agents like tramadol, which is a kind of a weak opioid but also has some what's called serotonin and norepinephrine, reuptake inhibition”— Sean Mackey
Dilaudid (hydromorphone)
hydromorphone
“We've got Dilaudid, which is a version of trade name for hydromorphone. So there's a slew”— Sean Mackey
Vicodin
AbbVie
“Doc cut her off from a little bit of Vicodin that she was taking intermittently for some back pain that had been well managed”— Sean Mackey
Charlotte's Web (CBD strain)
Stanley Brothers
“there's a strain of cannabis where it's pure CBD, no THC. I think they call it Charlotte's Web... it seems to be effective for the treatment of certain forms of pediatric epilepsy”— Andrew Huberman
Acetyl-L-carnitine
various supplement brands
“for neuropathic pain, acetyl-l-carnitine is one of them... it's one of the few over-the-counter agents that actually had disease modifying properties”— Sean Mackey
Alpha lipoic acid
various supplement brands
“Alpha lipoic acid is another one... it is a T type calcium channel modulator... it can have some benefit for neuropathic pain”— Sean Mackey
Creatine
various supplement brands
“creatine has shown in small pilot studies some benefit in fibromyalgia and some other types of conditions”— Sean Mackey
Fish oil (omega-3s)
various supplement brands
“Fish oil, the omega 3s have been found to be beneficial around chronic pain”— Sean Mackey
Big reveals from this episode
- Mackey's core message: what happens in your neck or shoulder is not pain but nociception; pain only exists once signals reach the brain.
- Swearing has been shown in studies to actually reduce pain.
- Introduces 'conditioned pain modulation' / DNIC: pain inhibits pain, so a distant painful stimulus can dampen primary pain.
- The central 'Mackey tip': learning the distinction between hurt and harm is critical to pain management.
- Shares that food poisoning at a Mexican restaurant left him with severe two-week abdominal pain from anything in the onion family.
- His study with Art Aron found viewing a photo of a new romantic partner is a powerful analgesic, working through addiction-reward circuits.
- Argues cutting patients off opioids drove a doubling of deaths in California as patients turned to black-tar heroin and illicit fentanyl.
- Reveals his life mission with partner Beth Darnall: a free digital platform and brief CBT intervention to bring quality pain care to everyone.
Worth remembering
- Chronic pain affects about 100 million Americans and costs roughly half a trillion dollars a year in medical expenses.
- NSAIDs like ibuprofen are technically anti-inflammatory / anti-hyperalgesic drugs, not true analgesics like opioids.
- Acetaminophen (Tylenol) is gentle on the stomach but you should not exceed about 4,000 mg per day due to liver risk.
- In one study, male students showed higher heat-pain thresholds when an attractive woman delivered the stimulus.
- Visceral-somatic convergence explains referred pain, like heart-attack pain radiating into the left arm.
- U.S. physicians get about seven hours of pain education in medical school, while veterinarians get around forty.
- Cannabis remains a Schedule I drug, which Mackey argues should be reclassified to Schedule II mainly to make it easier to research.
- Acetyl-L-carnitine is one of the few over-the-counter agents shown to be disease-modifying, improving nerve conduction in diabetic neuropathy.
- Mackey co-led the National Pain Strategy, which got overshadowed when the CDC opioid guidelines were released at the same time.