Peter Attia MD345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery
CHAPTERS
- 0:00 – 9:41
Defining pain: from Descartes to the biopsychosocial model
Peter Attia opens by asking how to define pain, and Sean Mackey gives the formal definition and adds that pain is the great motivator. He traces the dualistic model from René Descartes and explains why the move to a biopsychosocial view matters, especially for people with chronic pain who were stigmatized.
- •Formal definition: an unpleasant sensory and emotional experience associated with actual or potential tissue damage
- •Mackey says pain is the great motivator and keeps us alive
- •Descartes' dualism treated the mind as a passive receptacle, and Mackey calls it utterly wrong
- •Surgeons are increasingly recognizing that what patients bring to the operating table affects their pain
- •Chronic pain patients, especially women, were labeled histrionic or told it was all in their head
- 9:41 – 16:18
Nociceptors, C fibers and A delta fibers
Mackey explains nociceptors as transducers and contrasts fast, sharp A delta fibers with slow, burning, unpleasant C fibers. Attia checks the role of the spinal reflex and whether pain would persist without C fibers.
- •Nociceptors convert pressure, heat, cold and pH changes into electrochemical impulses
- •C fibers are slow (about 1 m/s) and A delta fibers are about ten times faster
- •A delta fibers give sharp, well-localized pain and trigger withdrawal reflexes
- •C fibers carry the hot, burning, unpleasant quality
- •Pain is evolutionarily redundant, so knocking out one pathway doesn't remove pain
- 16:18 – 24:02
Consciousness, anesthesia and nociception without pain
Attia asks whether consciousness is necessary for pain, and Mackey says yes. They discuss how anesthesia combines inhaled agents and opioids, why an unconscious patient still has nociception and a stress response, and how muddy the question becomes for animals like goldfish.
- •Mackey firmly believes a conscious brain is needed to experience pain
- •Under anesthesia there is no pain but plenty of nociception and a stress response
- •Inhaled anesthetics and opioids work synergistically through different mechanisms
- •Surgery is described as a controlled injury
- •Defining pain in animals gets muddy, so Mackey stays with humans
- 24:02 – 35:17
Four types of pain: nociceptive, visceral, neuropathic and nociplastic
Mackey categorizes pain into buckets and explains how each behaves and is treated. He covers referred visceral pain, neuropathic pain, drugs borrowed from neurology such as gabapentin, and the newer nociplastic category.
- •Nociceptive pain is localized, time-limited and responds to NSAIDs, acetaminophen and opioids
- •Visceral pain is diffuse and shows viscerosomatic convergence, such as shoulder pain from diaphragm irritation
- •Neuropathic pain from nerve injury is burning, shocklike and treated with anticonvulsants
- •Nociplastic pain is thought to reflect central processing dysfunction in conditions like fibromyalgia
- •Mackey suspects peripheral drivers will eventually be found for nociplastic conditions
- 35:17 – 41:00
fMRI biomarkers and the distributed pain network
Attia asks whether pain can be measured objectively, and Mackey describes his work building brain-imaging biomarkers with machine learning. He explains that no single pain region exists, and that the aim is predicting treatment response and future trajectory, not replacing self-report.
- •Mackey bet against fMRI pain signatures but his students showed they work
- •Pain activates a distributed network including thalamus, insula, anterior cingulate and S1
- •Biomarkers aim to predict treatment response, future state and vulnerability to injury or surgery
- •Patient self-report remains the standard for knowing if someone has pain
- 41:00 – 57:21
Evolution of pain, empathy and the brain's role in processing
Attia and Mackey discuss why C fibers act as a longer-term harm alarm, the evolutionary logic of pain, empathy and childbirth. Mackey then walks through the brain regions that generate the pain experience.
- •C fibers act as a longer-term alarm reminding you not to repeat harmful behavior
- •Humans developed empathy for pain, which was beneficial to the species
- •The thalamus acts like Grand Central Station for sensory input
- •The anterior cingulate handles unpleasantness and salience detection
- •The insula and amygdala integrate emotion, cognition and threat
- 57:21 – 1:04:30
Gate Control Theory, TENS and individual variability
Mackey explains Gate Control Theory and how A-beta touch fibers inhibit pain signals, which is why rubbing an injury helps and how TENS works. They discuss the wide variation in pain ratings for identical stimuli, including Attia's day-to-day cold plunge experience.
- •A-beta touch fibers inhibit nociceptive input in the spinal cord
- •TENS units exploit this and tend to work best for nociceptive musculoskeletal pain
- •A study applying a 48-degree stimulus to 500 people produced ratings from 0 to 10
- •Nociception may have little to do with the experience of pain
- •Pain experience varies within a person from day to day, driven by brain state
- 1:04:30 – 1:14:07
Pain tolerance, catastrophizing, sleep and other modulators
The conversation turns to society's admiration of high pain tolerance and to modality-specific sensitivity. Mackey lists factors that amplify pain, including catastrophizing, depression, glucose control, inflammation and sleep deprivation.
- •Society values stoicism, and Mackey describes it in his own upbringing
- •Pain sensitivity can be modality specific, such as heat versus cold
- •Catastrophizing is among the most predictive factors for amplified pain
- •Poor glucose control predicts diabetic neuropathic pain and inflammation causes peripheral sensitization
- •Sleep loss shifts the pain set point and impairs prefrontal modulation
- 1:14:07 – 1:20:28
Peter's personal story of back injury and opioid dependence
Attia recounts his disc herniation in medical school, the failed surgeries, a terrifying new pain, and being on 320 mg of OxyContin daily. He says the expectation of what the pain meant for his life became worse than the pain itself.
- •A large L5-S1 disc fragment compressed the S1 nerve root
- •Three operations followed, then a new pain Attia likened to his testicles being torn out
- •He was on roughly 320 mg of OxyContin per day and lay on the floor
- •He watched his future as a surgeon disappear
- •He calls it the best, worst experience of his life
- 1:20:28 – 1:33:19
NSAIDs, COX-2 inhibitors and acetaminophen
Mackey explains how NSAIDs reduce the inflammatory soup and notes that science is questioning whether blunting inflammation hinders healing. They discuss Vioxx, dosing, combining ibuprofen with acetaminophen, and individual variability in response.
- •NSAIDs inhibit cyclooxygenase and reduce prostaglandin-driven inflammation
- •Evidence suggests NSAIDs might delay healing, so the choice depends on function
- •Mackey and Attia lament the loss of Vioxx
- •Acetaminophen and ibuprofen can be combined for synergy, with liver and kidney cautions
- •Responses to different NSAIDs vary by individual
- 1:33:19 – 1:48:57
Muscle relaxants, gabapentinoids, antidepressants and defining chronic pain
Attia raises baclofen and other muscle relaxants, then they cover gabapentin and pregabalin, a definition of chronic pain, and antidepressants such as tricyclics.
- •Baclofen is one of the safest muscle relaxants and can be used long term with monitoring
- •Gabapentin and pregabalin turn down central signaling and have no lethal dose, though they sedate
- •Gabapentin absorption maxes out around 1,000 mg per dose, while pregabalin has linear kinetics
- •Chronic pain is defined as pain persisting beyond expected tissue healing
- •Tricyclics work on serotonin, norepinephrine and sodium channels, not just mood
- 1:48:57 – 2:12:59
Opioids: the nuanced case, perfect storm and perioperative care
Attia asks for the most responsible case for oral opioids, and Mackey says he is pro-patient, not pro- or anti-opioid. He describes the perfect storm behind the crisis, how acute pain services and nerve blocks reduce opioid use, and vulnerability factors for persistent use.
- •Mackey describes the opioid crisis as a perfect storm, not a single villain
- •Pressures included early discharge, minimal pain training, satisfaction scores and bad actors
- •Acute pain services use regional anesthesia, catheters and ketamine to reduce opioid need
- •Preoperative depression, anxiety, catastrophizing and early trauma predict persistent opioid use
- •Mackey wants studies on for whom opioids work, but funding is lacking
- 2:12:59 – 2:21:08
Acupuncture and cannabis
Mackey gives his take on acupuncture as safe and worth trying if affordable, with unpredictable responders. He then discusses cannabis, citing limited trials, his clinic's observational data and the regulatory barriers of Schedule I status.
- •Acupuncture helps some patients, and Mackey can't predict who
- •Sham acupuncture uses a Streitberger needle as a placebo
- •Dry needling is distinguished from acupuncture, with Mackey linking it to trigger point injections
- •Cannabis trials are few and show short-term benefit in neuropathic pain, while patients on cannabis at Stanford fare worse in observational data
- •Mackey favors moving cannabis to Schedule II or III to ease research
- 2:21:08 – 2:44:38
Fibromyalgia and low-dose naltrexone
Attia introduces fibromyalgia, and Mackey describes its features, prevalence context and abnormal pain modulation. They then discuss treatments, focusing on low-dose naltrexone, its proposed microglial mechanism, a striking patient case, and its possible relevance to neurodegeneration.
- •Fibromyalgia is a syndrome with widespread pain, fatigue, fog and sleep disturbance, with unknown mechanisms
- •Impaired conditioned pain modulation is seen in fibromyalgia
- •Treatments include TCAs, duloxetine and low-dose naltrexone
- •LDN at 4.5 mg is proposed to block microglial toll-like receptor 4, though Dan Clauw disagrees
- •LDN is cheap, safe, compounded, and Attia asks about mild cognitive impairment
- 2:44:38 – 3:07:07
Peter's recovery and breaking the pain cycle
Attia tells how he met Mackey and was treated with a lidocaine infusion and spinal injections, then rebuilt through rehab. They discuss catastrophizing, the interplay of procedures and rehabilitation, and why setbacks are not permanent.
- •Injections along the spine let Attia stand pain-free for the first time in three months
- •Procedures broke the cycle, but rehabilitation did the lasting work
- •Mackey says he never reaches a point of telling patients we're done
- •Catastrophizing involves amplification, rumination and helplessness and affects prefrontal circuits
- •Attia tells patients setbacks will pass and recovery looks like the S&P 500
- 3:07:07 – 3:15:35
Sean's cluster headaches and closing reflections
Mackey shares his experience with cluster headaches and how learning about them gave him self-efficacy and reduced fear. The episode closes with reflections on empathy, the value of focusing on pain in medicine, and mutual thanks.
- •Cluster headaches recur every two to three years with intense pain and agitation
- •Mackey feared a brain tumor before learning what they were
- •Abortive treatments include triptans and high-flow oxygen
- •Knowledge and preparation gave him control and lessened fear
- •Attia says chronic pain can be inflammatory to the psyche and distinguishes pain from discomfort
