How do over-the-counter painkillers like ibuprofen work to reduce pain?

NSAIDs like ibuprofen are technically anti-inflammatory and anti-hyperalgesic drugs. They reduce inflammation and decrease the sensitization of injured areas in the periphery and spinal cord, rather than directly blocking pain signals in the brain. They are not true analgesics like opioids.

When should I take painkillers, and how much is too much?

The threshold for taking painkillers is when pain significantly impacts your quality of life, daily activities, and ability to sleep. It's crucial to balance pain relief with the healing process. Take the lowest effective dose, always with food and plenty of fluids, and consult a clinician if you have pre-existing conditions or for severe injuries.

Can rubbing or shaking an injured area reduce pain?

Yes, this is explained by the gate control theory of pain. Activating touch fibers (A-beta fibers) through rubbing or shaking sends signals to the spinal cord that inhibit the nociceptive (pain) signals coming from the injury site, effectively reducing pain perception. This is a form of neuromodulation.

Do men and women experience pain differently, or have different pain thresholds?

On average, men tend to have slightly higher pain thresholds to stimuli like heat than women, but this difference is small. Individual variability within genders is much greater than the average difference between them, meaning there's significant overlap in pain experiences.

How does anxiety affect pain perception?

Increased anxiety generally increases one's perceived pain. The brain's emotional and cognitive state significantly shapes incoming nociceptive signals, leading to a more intense subjective experience of pain during anxious states.

What is the difference between 'hurt' and 'harm' in the context of pain?

It's critical to distinguish 'hurt' (painful sensation) from 'harm' (tissue injury or damage). Pain can be present without ongoing tissue damage. Understanding this distinction can reduce fear and anxiety, allowing for better management, particularly in chronic pain conditions where tissue healing has already occurred.

What role does nutrition play in managing pain?

Nutrition is critical; healthy eating, anti-inflammatory diets, and avoiding food triggers can significantly impact pain. Gut infections, for example, can sensitize individuals to certain food antigens, leading to chronic abdominal pain. Elimination diets and journaling can help identify these triggers.

What are endogenous opioids, and how do they relate to opioid medications?

Endogenous opioids, like enkephalins and endorphins, are natural painkillers produced by our bodies. Exogenous opioids (drugs like morphine or oxycodone) are synthetic or naturally derived compounds from the poppy that bind to the same opioid receptors in the brain, spinal cord, and periphery to produce their analgesic effects.

What are the common prescription opioids, and why is the opioid crisis so complex?

Common prescription opioids include morphine, oxycodone (OxyContin), fentanyl, tramadol, and hydromorphone. The opioid crisis is complex due to historical overprescribing, inadequate pain education for physicians, the emergence of a black market after patient abandonment, and the rise of illicit fentanyl as a major driver of overdose deaths.

Is cannabis (THC, CBD) effective for pain management?

In controlled lab settings, cannabis has shown to reduce neuropathic pain. However, large-scale studies show mixed results, and much is unknown about its efficacy for broader pain types. The specific ratios of THC/CBD and unregulated dosing make it challenging to study and recommend broadly.

Does acupuncture help with pain?

Acupuncture has shown some scientific basis for effectiveness in certain pain conditions. While the exact mechanisms are not fully understood, studies indicate it can activate peripheral adenosine receptors and engage different brain regions compared to sham acupuncture. It's often recommended as a complementary approach if affordable and performed by a skilled practitioner.

What is 'pacing' in chronic pain management?

Pacing is a critical technique where individuals with chronic pain set small, achievable activity goals daily and stick to them, regardless of how they feel. This avoids the 'boom and bust' cycle of overexertion on good days followed by severe pain and inactivity, which often leads to deconditioning and increased disability.

What non-prescription supplements are beneficial for pain?

Acetyl L-Carnitine and Alpha-Lipoic Acid have shown benefit for neuropathic pain. Vitamin C can reduce nerve pain after surgery. Omega-3 fatty acids (fish oil) and Creatine have also shown some promise in chronic pain and fibromyalgia, respectively, based on research.

What role do psychological therapies play in pain management?

Psychological therapies like Cognitive Behavioral Therapy (CBT), Mindfulness-Based Stress Reduction (MBSR), and Acceptance and Commitment Therapy (ACT) are absolutely crucial. They help teach coping skills, manage unhelpful thoughts, reduce anxiety and depression, and calm the sympathetic nervous system to reduce the overall pain experience.

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Tools to Reduce & Manage Pain | Dr. Sean Mackey

Andrew Huberman

Science & Technology8 min read177 min video

Jan 15, 2024|504,630 views|6,710|774

andrew huberman huberman lab podcast huberman podcast dr. andrew huberman neuroscience huberman lab andrew huberman podcast the huberman lab podcast science podcast pain management dr. sean mackey stanford university

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TL;DR

Pain is complex, involving sensory and emotional experiences shaped by the brain, treatable through diverse methods.

Key Insights

Pain is a subjective, individualized experience distinct from nociception (sensory signals) and involves both sensory and emotional components in the brain.

The brain integrates signals from the body and is influenced by emotions, cognition, and memory, making pain a distributed network phenomenon rather than localized to a single brain region.

Pain thresholds vary significantly among individuals, influenced by factors like anxiety, beliefs, expectations, and early life experiences, with men generally having higher heat pain thresholds than women, though individual variability is greater than group averages.

Mechanical interventions like rubbing or shaking an injured area, and therapeutic use of heat and cold, activate neural pathways in the spinal cord and brain to modulate pain.

Nutritional choices, such as anti-inflammatory diets and identifying specific food triggers, play a critical and often underappreciated role in managing chronic pain, exemplified by a personal account of digestive pain relief through dietary changes.

Opioids, both endogenous and exogenous, are powerful analgesics with complex societal implications; while they can destroy lives, they also transform others, highlighting the need for individualized, patient-centered care and careful prescribing practices.

DEFINING PAIN: SENSORY AND EMOTIONAL EXPERIENCE

Pain is not merely a physical sensation but a complex, subjective experience with both sensory and emotional components. This individual nature means one person's pain differs significantly from another's. While initial signals (nociception) originate in the body's sensors (nociceptors), the actual experience of pain is constructed in the brain, integrating these signals with emotions, cognitions, and memories. Chronic pain, affecting millions and costing billions, represents a significant societal challenge, underscoring the need for a deeper understanding beyond the outdated biomedical model of a direct stimulus-response relationship.

THE BRAIN-BODY CONNECTION IN PAIN

The origin of pain is fundamentally in the brain, where electrochemical impulses from nociceptors are processed and given subjective meaning. Nociceptors, found throughout the body, detect various stimuli (temperature, pressure, pH changes) and transmit signals via fast A-delta and slower C-fibers to the spinal cord, and then to the brain. Crucially, the brain is not a passive recipient; it actively shapes these signals into the unique experience of pain. There isn't a single 'pain center,' but rather a distributed network of brain regions, including the insular and cingulate cortices and the amygdala, contributing to the pain 'matrix' or network.

MECHANISMS OF PAIN RELIEF: DRUGS AND PHYSICAL INTERVENTIONS

Painkillers operate at different levels. Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen primarily reduce inflammation and peripheral sensitization in the body and spinal cord, rather than directly blocking pain perception. Opioids, on the other hand, are true analgesics acting on opioid receptors in the periphery, spinal cord, and brain. Mechanical interventions, such as rubbing an injured area, activate fast-conducting A-beta nerve fibers, engaging a spinal cord mechanism (gate control theory) that inhibits nociceptive signals. This neuromodulation can be mimicked by devices like TENS units and even simple actions like shaking a limb or applying water.

HEAT, COLD, AND PAIN MODULATION

Therapeutic heat and cold are common pain management tools. Cold applications, typically recommended for the initial 48 hours post-injury, reduce inflammation by slowing nerve firing and decreasing the release of inflammatory chemicals like prostaglandins. Heat, conversely, increases blood flow and relaxes muscles, often providing comfort. Both methods have individual variability in effectiveness, and their use should be within reason to avoid adverse effects like frostbite or burns. The efficacy of 'extreme' cold exposure (e.g., ice baths) for general pain threshold modulation is an intriguing area, with questions remaining about its cross-modality effects on different pain stimuli.

INDIVIDUAL PAIN THRESHOLDS AND COGNITIVE INFLUENCES

Pain threshold, defined as the stimulus intensity at which pain is first perceived, varies widely. Research indicates general differences between men and women (e.g., men often have higher heat pain thresholds), but individual variability within these groups is much greater. This threshold is significantly influenced by cognitive and emotional states, such as anxiety, beliefs, expectations, and past traumatic experiences. Increased anxiety generally heightens perceived pain. Cognitive control and training, including physical exercise and specific mental manipulations (like the famous 'attractive experimenter' scenario), can alter pain thresholds over time, highlighting the brain's profound role in pain experience.

PSYCHOLOGICAL APPROACHES TO PAIN MANAGEMENT

Psychological strategies offer powerful top-down mechanisms for pain control. Attentional distraction, by engaging in enjoyable activities, effectively reduces pain by activating prefrontal and cingulate cortical networks. However, its effectiveness wanes at night during sleep. Mindfulness-based stress reduction (MBSR) involves a non-judgmental acceptance of pain, which has shown efficacy in chronic conditions like low back pain. Cognitive behavioral therapy (CBT) involves reframing the meaning of pain, shifting perception from 'damaging' to 'hurting but not harming.' These distinct approaches engage different brain circuits, emphasizing the need for personalized psychological interventions.

HURT VERSUS HARM: A CRITICAL DISTINCTION

A vital concept in pain management is distinguishing between 'hurt' and 'harm.' Many chronic pain conditions involve pain that is distressing but not indicative of ongoing tissue damage or injury. Education about this distinction can significantly reduce fear and anxiety, empowering individuals to resume activities. For instance, a Morton's neuroma, though painful, doesn't cause harm, allowing a patient to return to activities like tennis. This principle extends to emotional pain, where understanding whether an experience is merely 'hurtful' or psychologically 'damaging' can influence one's response and recovery, necessitating a holistic approach to address both physical and emotional well-being.

THE INTERPLAY OF EMOTION, STRESS, AND PAIN

Emotional states exert profound influence on pain. Stress, both acute and chronic, can exacerbate pain by activating the sympathetic nervous system, leading to physiological changes like increased heart rate, muscle tension, and cortisol release. Chronic stress is particularly detrimental, impacting end organs and contributing to real, physical pain. Conversely, positive emotions significantly reduce pain. Studies have shown that passionate love, by engaging reward-based brain circuits (e.g., nucleus accumbens, amygdala), acts as a potent analgesic. This highlights that psychological phenomena are deeply rooted in neurobiological processes, supporting a holistic approach to pain care that addresses mental well-being alongside physical symptoms.

NUTRITION AND PAIN: AN UNDERAPPRECIATED LINK

The role of nutrition in pain management is increasingly recognized as critical. Anti-inflammatory diets and the avoidance of specific food triggers can profoundly impact chronic pain. Personal accounts, such as developing chronic abdominal pain post-infection and finding relief through avoiding the onion family, underscore the individualized nature of dietary influences. Elimination diets, carefully implemented, can help identify such triggers. The emerging understanding of how gut infections can alter genetic expression related to food antigen sensitivity points to a complex interplay between the microbiome, immune system, and pain, suggesting a public health issue that warrants further scientific exploration and funding.

VISCERAL AND NEUROPATHIC PAIN

Visceral pain, originating from internal organs, differs from somatic pain (from the body surface or musculoskeletal system) in its diffuse localization due to broader receptive fields. This diffusion can lead to 'viscerosomatic convergence,' where internal organ pain is perceived as external, such as pelvic pain radiating to the lower back or heart attack pain in the left arm. Neuropathic pain, arising from damage to peripheral or central nerves, presents with distinct qualities like shooting, stabbing, or burning sensations, and is often challenging to treat. Understanding these different pain categories is crucial for accurate diagnosis and tailored management strategies.

OPIOIDS: USE CASES AND CONCERNS

Endogenous opioids (e.g., endorphins) are natural painkillers, but exogenous opioids (e.g., morphine, oxycodone) derived from the poppy or synthesized, are potent prescription drugs. While highly effective for severe pain, historical overprescribing contributed to the 'opioid crisis,' which is now predominantly driven by illicit fentanyl. Opioids are a nuanced tool, capable of transforming lives by relieving suffering, particularly in end-of-life care or intractable chronic pain, but also capable of creating addiction and destroying lives. Responsible use emphasizes individualized, case-by-case assessment, typically as a last resort after other therapies have failed, and careful monitoring.

CONTROVERSIAL ANALGESICS: KATYUM AND CANNABIS

Kratom, a natural substance with opioid-like properties, is a contentious topic. While some users claim it helps them manage pain or addiction to prescription opioids, concerns exist regarding its unknown purity, dosage, and increasing association with overdose deaths, particularly in poly-substance use. Further research is needed to determine its safety and efficacy. Cannabis also reduces neuropathic pain in controlled settings, but large-scale epidemiological studies show mixed results for general pain. Challenges include unregulated dosing, varying THC/CBD ratios, and its Schedule I status, which impedes research. Advocates suggest rescheduling cannabis to facilitate scientific study and harness its potential therapeutic benefits.

COMPLEMENTARY AND REHABILITATIVE THERAPIES

Pain management integrates diverse approaches. Complementary and alternative medicine (CAM) like acupuncture, despite unknown mechanisms, shows promise for some patients; its efficacy in activating peripheral adenosine receptors and distinct brain regions is being explored. Chiropractic care, while effective for some low back pain, has mixed data and risks associated with high-velocity manipulations, particularly in the neck. Physical and occupational therapy are crucial for long-term recovery, focusing on functional rehabilitation, improving body mechanics, and building endurance. 'Pacing' is a key strategy where patients gradually increase activity to avoid the debilitating cycle of overexertion and subsequent pain flares.

INTEGRATIVE PAIN MANAGEMENT AND THE FUTURE

A holistic, patient-centered approach to pain management involves integrating medications, nerve blocks/procedures, psychological/behavioral therapies, physical/occupational therapy, complementary/alternative medicine, and self-empowerment through education. Neutraceuticals like acetyl-L-carnitine, alpha-lipoic acid, vitamin C, fish oil, and creatine have shown benefits for specific pain conditions, often with disease-modifying properties. The future of pain medicine lies in a cultural transformation, advocating for the full implementation of national strategies that foster better education, communication, and integrated care. Technological platforms are being developed to bridge healthcare deserts by delivering high-quality, data-informed treatments and brief interventions, such as Empowered Relief, making effective pain management more accessible globally.

Mentioned in This Episode

●Supplements

●Products

●Software & Apps

●Organizations

●Concepts

●People Referenced

Common Questions

Pain is a complex, subjective experience involving both sensory and emotional components, uniquely processed by the brain. Nociception, on the other hand, refers to the electrical and electrochemical signals transmitted by sensory elements (nociceptors) in the body, which are not yet the conscious experience of pain until they reach the brain.

Topics

Health & Longevity Neuroscience & the Brain Mindset & Self-Improvement Mindfulness Anti-inflammatory Diet Chronic Pain Pain Management Neuropathic Pain Pain Perception Medicine & Clinical Opioid Crisis

Mentioned in this video

People

Rene Descartes

17th-century French philosopher who postulated a direct linkage between the body's stimulus and our actions/responses, a concept now understood to be incorrect in pain science.

Andrew Huberman

Professor of Neurobiology and Ophthalmology at Stanford School of Medicine and host of the Huberman Lab podcast.

Alan Adler

Engineer at Stanford and inventor of the AeroPress, known for creating unusual products like the Aerobie frisbee.

Ronald Melzack

Co-defined the 'gate control theory of pain' in the 1960s, explaining how non-painful input can close the 'gates' to painful input.

Robert Sapolsky

Stanford professor renowned for his work on chronic stress and its detrimental effects on the body and brain.

Sean Mackey

Medical doctor and PhD, Chief of the Division of Pain Medicine and Professor of Anesthesiology and Neurology at Stanford University School of Medicine. Guest on the podcast.

Patrick Wall

Co-defined the 'gate control theory of pain' in the 1960s, a foundational concept in understanding pain modulation.

John Burns

Researcher who categorized anger into 'anger in' (internalized) and 'anger out' (expressed), with 'anger in' potentially being more detrimental in the context of pain.

Lynn Nguyen

GI pain doctor at Stanford who pointed Dr. Mackey to research about gut infections changing genetic expression related to food antigen sensitization.

Justin Sonnenberg

A world expert on the gut microbiome at Stanford, whose collaboration helps in biomarker studies for characterizing individuals' health.

Art Aron

Researcher known for studying passionate love, who collaborated with Dr. Mackey on a study exploring the analgesic effects of love.

Beth Darnell

Dr. Mackey's partner who developed 'Empowered Relief,' a brief intervention that condenses eight weeks of cognitive behavioral therapy into two hours.

Jon Kabat-Zinn

Developer of Mindfulness-Based Stress Reduction (MBSR), a program that emphasizes non-judgmental acceptance and has shown efficacy for various conditions including chronic pain.

Hannah Watford

A Stanford allergist who frequently sees cases of food sensitivities triggered by events later in life, indicating a potential public health issue.

Jared Younger

A former postdoc in Dr. Mackey's lab, now a professor at the University of Alabama, who led a study showing passionate love as a powerful analgesic.

Mark Wallace

Runs pain management at UC San Diego and has developed specific THC to CBD ratios for pain relief.

Drugs & Medications

Naproxen

Another over-the-counter NSAID, with a slightly longer half-life than ibuprofen, showing individual variability in effectiveness.

Advil

A brand name for Ibuprofen.

Ketorolac

A prescription-only NSAID, often used for moderate to severe acute pain.

Ketamine

A therapeutic drug similar to PCP, widely used therapeutically for various conditions though typically a Schedule III drug.

acetaminophen

An over-the-counter medication (Tylenol) that does not have the same GI side effects as NSAIDs but requires caution not to exceed 4,000mg/day to protect liver function.

Tylenol

A brand name for acetaminophen, which has a slightly different, more centrally acting mechanism for pain relief and is safer on the stomach than NSAIDs but can be harmful to the liver in high doses.

Celecoxib

A selective COX-2 inhibitor, a prescription NSAID that is less irritating to the stomach compared to ibuprofen or naproxen.

Concepts

Mindfulness-Based Stress Reduction

A program developed by Jon Kabat-Zinn, shown effective for anxiety, depression, and pain by promoting a non-judgmental, accepting approach to one's experiences.

Morton's Neuroma

A fibrous thickening of tissue around nerves in the foot, causing significant pain but not causing harm, which can often be managed by understanding the hurt vs. harm distinction.

FODMAPs

A group of carbohydrates that can cause digestive issues and pain for some individuals, requiring identification and avoidance as part of dietary management.

Conditioned Pain Modulation

A phenomenon where engaging a nociceptive (painful) stimulus in a different, distant site from the primary pain can inhibit the original pain, thought to involve brain stem circuits.

Prostaglandins

Chemical mediators released during injury that amplify nociceptors and contribute to inflammation and pain sensitization. Caffeine also impacts this pathway to aid with headaches.

Cognitive Behavioral Therapy

A therapeutic approach that helps individuals recognize and interrupt unhelpful thoughts and patterns around pain, incorporates goal setting, pacing and relaxation techniques.

Supplements

omega-3s

Found to be beneficial for chronic pain, although high levels can reduce blood viscosity.

Ibuprofen

A non-steroidal anti-inflammatory drug (NSAID) that reduces sensitization in the periphery and spinal cord, but does not directly act as an analgesic for immediate pain blocking.

AG1

A vitamin, mineral, probiotic drink containing adaptogens, used to ensure adequate vitamin/mineral intake and support gut health and brain functioning.

Acetone L-Carnitine

A non-prescription compound found to be effective for neuropathic pain by acting on mitochondrial metabolism and health, described as having disease-modifying properties.

Creatine

Shown in small pilot studies to have some benefit in fibromyalgia and other pain conditions.

Aspirin

Functions as an anti-platelet agent at low doses (81mg/day), potentially benefiting heart health, and as an anti-inflammatory at higher doses (325mg or more).

Alpha-lipoic acid

A non-prescription compound with two mechanisms: a free radical scavenger and a T-type calcium channel modulator, beneficial for neuropathic pain and general well-being.

Vitamin C

When taken prophylactically before surgery, it can reduce the likelihood of certain nerve pain conditions post-operatively.

Companies

Levels

A continuous glucose monitor program that helps users see how foods and activities impact their blood glucose levels for better energy and long-term health.

BetterHelp

An online platform offering professional therapy with licensed therapists.

InsideTracker

A personalized nutrition platform that analyzes blood and DNA data to provide actionable directives for improving health based on metabolic factors, lipids, and hormones.

Products

Aeropress

A coffee maker, similar to a French press, that creates smooth-tasting coffee or tea and cleans up in less than 2 minutes.

Software & Apps

TENS device

Transcutaneous Electrical Neurostimulation (TENS) device activates touch fibers (A-beta fibers) to cause neuromodulation in the spinal cord, reducing nociceptive signals and pain.

Organizations

NIH

National Institutes of Health, a primary funding source for medical research, including studies on pain and behavioral therapies.