← The Peter Attia Drive

#345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery | Sean Mackey, M.D., Ph.D.

Apr 21, 2025 2h 47m 31 insights
<p><a href="https://peterattiamd.com/seanmackey/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=250421-pod-seanmackey&amp;utm_content=250421-pod-seanmackey-podfeed"> View the Show Notes Page for This Episode</a></p> <p><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=250421-pod-seanmackey&amp;utm_content=250421-pod-seanmackey-podfeed"> Become a Member to Receive Exclusive Content</a></p> <p><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&amp;utm_medium=referral&amp;utm_campaign=250421-pod-seanmackey&amp;utm_content=250421-pod-seanmackey-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Sean Mackey is a professor of pain medicine at Stanford University and the director of the Stanford Systems Neuroscience and Pain Lab, where his research explores the neural mechanisms of pain and the development of novel treatments for chronic pain. In this episode, Sean joins Peter for a wide-ranging discussion on the multifaceted nature of pain—as both a sensory and emotional experience—and its evolutionary purpose as a critical survival mechanism. He dives into how pain is transmitted through the nervous system, the different types of pain, and why different individuals perceive pain so differently. Sean shares insights into pain management strategies ranging from medications like NSAIDs and opioids to neuromodulation techniques such as transcutaneous electrical nerve stimulation (TENS). Additionally, this episode explores the interplay between sleep and chronic pain and the psychological and emotional dimensions of pain, and it includes a personal story from Peter about his own experience with pain and how Sean's expertise helped him more than two decades ago.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>The definition of pain, and how our understanding of pain has evolved from a simplistic body-mind separation to a nuanced biopsychosocial model [2:30];</li> <li>The biological mechanisms behind how we perceive pain [9:30];</li> <li>The role of consciousness in the perception of pain, and how nociception functions during unconscious states [14:30];</li> <li>The four types of pain [22:00];</li> <li>Using fMRI to identify objective biomarkers of pain in the brain [31:30];</li> <li>The evolutionary role of pain in human behavior and survival [36:00];</li> <li>How the brain processes and modulates pain signals, Gate Control Theory, the variability in individuals' pain perception, and effectiveness of neuromodulation techniques like TENS [41:00];</li> <li>The brain's influence on pain: the role of emotion, beliefs, sleep, and individual differences in perception and tolerance [53:45];</li> <li>Peter's personal journey with chronic back pain, and how the emotional consequences of pain can be more distressing than the pain itself [1:04:30];</li> <li>The pharmacology of common pain medications—NSAIDs, COX-2 inhibitors, and acetaminophen [1:09:30];</li> <li>Muscle relaxants: benefits, drawbacks, and personalized strategies [1:20:30];</li> <li>The definition of chronic pain [1:29:15];</li> <li>The role of antidepressants in pain management [1:30:15];</li> <li>Opioids: their controversial and nuanced role in pain management [1:33:45];</li> <li>Alternative therapies: acupuncture and cannabis [1:54:15];</li> <li>Fibromyalgia and chronic pain: clinical features, brain mechanisms, and emerging treatments like low-dose naltrexone [2:01:00];</li> <li>Possible brain benefits of low-dose naltrexone (LDN) for people with mild cognitive impairment [2:15:00];</li> <li>Peter's recovery from severe chronic pain—how he went from immobility and high-dose opioids to full functionality [2:20:15];</li> <li>Breaking the pain cycle: how physical rehabilitation and psychological recovery work together in chronic pain treatment [2:30:45];</li> <li>Sean's struggle with cluster headaches, and the value of knowledge, preparation, and empathy in both managing chronic pain and caring for patients [2:39:15]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p>
Actionable Insights

1. Reject Dualistic Pain Model

Discard the outdated dualistic model of pain that separates body and mind, and instead understand pain as an integrated biopsychosocial phenomenon.

2. Acknowledge Individual Pain Variability

Understand that the intensity of a physical stimulus (nociception) may have little correlation with an individual’s actual experience of pain, as perception varies widely from person to person.

3. Acknowledge Psychological Pain Influence

Recognize that psychological and emotional factors, including early life experiences, significantly influence pain perception, even in the face of identical physical stimuli.

4. Manage Mental State for Pain

Be aware that your mental state, including anxiety, apprehension, and sleep quality, significantly influences your experience and perception of pain.

5. Prioritize Sleep to Reduce Pain

Ensure adequate sleep, as sleep deprivation significantly alters the brain and spinal cord’s set point for pain perception, amplifying pain and impairing its modulation.

6. Adopt Anti-Inflammatory Diet

Consider your diet’s role in pain, as consuming foods that cause inflammation can lead to peripheral sensitization, amplifying nociceptor activity and increasing pain perception.

7. Control Glucose for Neuropathic Pain

For individuals with diabetic neuropathic pain, strict glucose control is a major predictor of pain management, as high blood sugar damages nerve fibers involved in pain.

8. Educate Yourself on Pain Condition

Learn as much as possible about your specific pain condition to become informed, which can reduce fear, prevent amplification of pain, and build self-efficacy, significantly improving your quality of life.

9. View Pain Setbacks as Temporary

When experiencing pain setbacks, adopt the mindset that they are not permanent; this builds confidence, reduces catastrophizing, and helps you make necessary adjustments, knowing the discomfort will eventually pass.

10. Prioritize Social Connection for Pain

Actively combat social isolation and prioritize social functioning, as it plays a key role in managing overall pain and improving quality of life.

11. Request Pre-Surgical Pain Plan

Before elective surgery, proactively ask your surgeon about pain management, requesting an interface with an acute pain service to develop a pre-surgical plan, including regional anesthetics, to optimize recovery and minimize opioid use.

12. Address Pre-Surgical Psychological Vulnerabilities

Be aware that preoperative psychological factors like depression, anxiety, catastrophizing, and trauma history are strong predictors of persistent pain and opioid use after surgery, and addressing these can improve outcomes.

13. Trial Low-Dose Naltrexone for Chronic Pain

Consider a trial of Low-Dose Naltrexone (LDN) at 4.5mg for chronic pain conditions like fibromyalgia, as it may reduce neuroinflammation with minimal side effects (vivid dreams) and low cost.

14. Utilize Gabapentinoids for Neuropathic Pain

For neuropathic pain, consider gabapentin or pregabalin, which turn down pain signals in the spinal cord and brain and can aid sleep, though elderly patients should be cautious of falls.

15. Use Antidepressants for Pain Modulation

Consider specific antidepressants, particularly tricyclics (e.g., desipramine, nortriptyline) and SNRIs (e.g., duloxetine), for pain management, as they modulate neurotransmitter systems involved in pain regardless of mood.

16. Opioids as Last-Resort Tool

Consider opioids as a specific tool for severe pain, such as end-of-life or cancer pain, but avoid them as a first-line agent due to their risks and the availability of many other pain management options.

17. Combine Acetaminophen and Ibuprofen

For enhanced pain relief, combine acetaminophen and ibuprofen due to their different mechanisms of action, which allows for lower doses of each while achieving synergistic effects.

18. Judicious NSAID Use for Function

Use NSAIDs like ibuprofen or naproxen to reduce inflammation and improve function if pain is significant, but be mindful that for minor pain, avoiding them might support natural healing processes.

19. Experiment with NSAID Types

Due to individual variability in response and how different NSAIDs permeate tissues, experiment with various types (e.g., naproxen, ibuprofen) to find which is most effective for your pain.

20. Limit Acetaminophen with Alcohol/Liver Issues

Limit acetaminophen intake, especially if you have liver dysfunction or consume large amounts of alcohol, with a recent push to reduce the maximum daily dose to two grams.

21. Consult Doctor for NSAID Use

Before prolonged use of NSAIDs (e.g., 800mg ibuprofen three times daily for 1-2 weeks), consult your doctor, especially if you are older or have kidney or GI issues.

22. Consider Baclofen for Muscle Pain

For acute muscle pain, consider Baclofen as a safe, non-habit-forming muscle relaxant, but continuously evaluate its long-term benefit and consider weaning if no longer effective.

23. Utilize TENS for Musculoskeletal Pain

For nociceptive musculoskeletal pain, consider using a TENS (Transcutaneous Electrical Neural Stimulation) unit, placing pads over the painful area to activate A-beta fibers and achieve neuromodulatory pain relief.

24. Rub Injured Area for Pain Relief

When experiencing pain from an injury, rub the affected area to activate A-beta touch fibers, which can inhibit pain signals in the spinal cord and reduce pain perception.

25. Differentiate Pain Signals’ Purpose

Understand that sharp, localized pain (A-delta fibers) prompts immediate withdrawal, while delayed, burning pain (C-fibers) serves as a long-term harm alarm to encourage healing and prevent re-injury.

26. Understand Pain’s Survival Role

Recognize pain as a fundamental, primitive survival mechanism that keeps us alive, rather than solely an unpleasant experience.

27. Understand Fibromyalgia’s Central Nature

Recognize fibromyalgia as a complex syndrome of widespread pain, fatigue, and cognitive issues, linked to abnormal central pain processing in the brain and often triggered by traumatic events.

28. Consider Acupuncture for Pain

If affordable and performed in a hygienic facility, consider trying acupuncture for pain, as some individuals find it effective for conditions like back pain, musculoskeletal pain, and migraines.

29. Approach Cannabis for Pain with Caution

Approach cannabis for pain relief with caution, as evidence is mixed; while some short-term benefits for neuropathic pain exist, current forms are not well-studied or standardized, and observational data suggests worse outcomes for chronic users.

30. Embrace Discomfort in Workouts

Actively engage in hard workouts and embrace the experience of physical discomfort, distinguishing it from chronic pain to build resilience and promote overall well-being.

31. Subscribe for Health Knowledge

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