Pain relief comes from more than meds. Dr. Sanjay Gupta explains your body’s natural painkillers

Nearly impossible to measure, quantify, convey, pain is a truly mysterious human sensation. For the last 25 years in my life as a neurosurgeon, I have seen a lot of pain and suffering firsthand, so much of it chronic, persistent and difficult to treat. That is why I spent the past three years digging deep into the complexities of pain, its relationship to the brain and strategies to combat it that you have probably never considered. For most of us, pain will be a reality at some point in our lives, but I am more convinced than ever that “It Doesn’t Have to Hurt,” which is the title of my new book, releasing on September 2. I am delighted to share a selection below. Then, on September 7, watch CNN at 8 p.m. ET to witness incredible cutting-edge innovations in pain relief in my new documentary, “Dr. Sanjay Gupta Reports: It Doesn’t Have to Hurt.” – Sanjay

When headaches or sore muscles strike us at home, we reach for everyday painkillers. Usually it’s something like ibuprofen, aspirin, or naproxen, all analgesics known in the medical world as nonsteroidal anti-inflammatories (NSAIDs). The most common non-NSAID pain reliever is acetaminophen, or Tylenol, which isn’t an anti-inflammatory but works well to reduce fever and is typically easier on the stomach. Even before reaching for those over-the-counter meds, we may ice a sore elbow or lower back, or soak in a hot tub to ease achy muscles or joints.

In the clinical setting, we certainly appreciate it when the dentist numbs our mouth with Novocain. We take anesthesia for granted when rolling into surgery (having had an IV sedative first), or receiving an epidural during childbirth — as my wife did for all three of our girls. Then, of course, there are post-op meds — including, when necessary, prescription opioids to manage acute pain through recovery. In all these ways, we’ve become accustomed to pain relief being an “outside job.” But in truth, elaborate biochemical systems, molecular mechanisms, and mind-body networks for pain control and prevention already exist within us, an “inside job” that science is only beginning to unpack.

Mind, body, brain, bones, and blood: every part of us is wired not only for pain but also for pain relief. It’s an incredible system that gets little attention, one I first experienced all those years ago while lying impaled on that spiked fence. Even before I went to the ER or received any medications, I could feel my body starting to soothe itself, my own healing mechanisms taking over. The pain didn’t disappear, but it came in waves, with periods of real relief in between. And then, simply having my mother arrive provided not just mental and emotional comfort but actual physical comfort too.

Having a caring person in your life can improve your resilience to pain, whereas isolation or loneliness can exacerbate it. I remember the first time one of my children got a shot. I didn’t even have to think about what to do: my first instinct was to comfort her with voice and touch.

Sometimes when we’re sidelined with a painful injury, a call from a friend or even just listening to music can make a difference in how we feel by flooding the brain’s pain-processing circuitry with positive feelings and emotions. Training your brain in this way is a crucial piece of the healing mix for pain relief.

Think of this healing mix as an expanded toolbox that goes beyond what most people consider the “real” tools for pain relief. The conventional conversation tends to focus on medications and medical interventions, but I want to bring your attention to other, less appreciated tools. Let’s start with your body’s built-in painkillers, the endogenous opioid system.

Your body’s natural painkillers: Endogenous opioids, placebos, and more

By now you know that opiates are some of the world’s most powerful painkillers. But what you may not know is that your body is adept at producing the natural form of these same chemicals. They’re called endorphins, a term that merges the Greek word endogenous (meaning “from within”) and morphine. Though endorphins are just one of several types of protein molecules with this painkiller quality, the word is often used to refer to them collectively. And as you’re about to learn, they can influence your mood as well as your perception of pain. Pump up the endorphins — decrease the pain.

The natural world serves as both an inspiration and a guide as scientists search for ways to tap into or mimic its unique problem-solving genius. A bird in flight, the strength of a spider’s web, a gecko’s sticky grip — all have served as models for scientific inventions. Bioinspired innovations are all around us, from skyscrapers to syringes.

Many years ago, when drug developers began to search for molecules and mechanisms that could safely reduce pain, they drew inspiration from our own human bodies and their endogenous opioid system. Keep in mind that in addition to reducing pain, the system is involved in emotional regulation and mood, neurogenesis (growth of new neurons in the nervous system), neuroplasticity, learning and memory, and the brain’s reward- processing system.

So how does it work? Opioids, whether endogenous or those found in narcotics (called exogenous opioids), bind to opioid receptors located on the outer membrane of nerve cells in the brain, spinal cord, and other organs. Like molecular keys in locks, when opioids bind to these receptors, they trigger a cascade of chemical changes within and between neurons, producing feelings of pleasure as well as pain relief.

The receptors are also present in the brain’s reward circuitry, which uses the neurotransmitter dopamine to tag experiences of pleasure. That is why we often want to repeat certain experiences. That’s true of all opioids. But endogenous opioids have an insider advantage as a natural part of the body’s interwoven system for pain modulation. Like software programs that are part of the same operating system, they mesh seamlessly. Evolution has fine-tuned their actions with meticulous precision, including the way the body metabolizes them so they can constantly turn on or off, as well as micromanaging doses. This prevents some of the complications that arise with outside opioid medications, including constipation, brain fog, slowed breathing, nausea, and drug tolerance and dependence.

Nature even added an emergency survival tool: stress-induced analgesia that temporarily suppresses pain. Under extreme stress, the fight-or-flight hormones aggressively trigger the endogenous opioid system, which greatly reduces the pain. The pain does eventually come back when this emergency hormonal response subsides, but in the meantime, traumatic injuries may not immediately register as painful to a wounded soldier or a kid impaled by a fence. “When you look at the release of norepinephrine and opioids for the flight and fear response — it is one of the most potent analgesic, anti-pain molecules that exists,” says Daniela Salvemini, Ph.D., William Beaumont Professor and director of St. Louis University Institute for Translational Neuroscience. Having devoted her career to understanding the mechanisms that drive neuropathic pain, and the molecules that may relieve it, she remains in awe of “what our bodies have given us as survival kits.” For some, it kicks in right away, and for others, it takes considerably longer, but everyone appears to have this naturally occurring plan B for the most dire circumstances.

A variety of stressors, not just physical pain, can trigger the endogenous opioid system. These include psychological, neurological, physiological, even ontological (spiritual or metaphysical) factors, which can activate the system to:

Because most of these endogenous opioid benefits take place at a subconscious level, these processes have long been assumed to be inaccessible, meaning not something you can control in the same way you can pop a pill. But now we know that simply moving — jogging or going for a brisk walk — can trigger an endorphin release that delivers the rush we call an endorphin high, or “runner’s high.” Gazing at a sunset or a loved one can help do it as well. You can activate your own endogenous opioid system and experience the surprising power of your neural circuits to disrupt pain and amplify pleasure. We now know that just by choosing to focus on something beautiful or positive, a wondrous cascade of events unfolds in our bodies that can change our experience of pain.

Let’s take a closer look at the term placebo effect, which many think of as a fake pill or sham treatment used in clinical research to compare effects with the “real” treatment being studied. Researchers typically compare the two, because any health improvements from a new or experimental medication must outperform the placebo by a measurable amount before being deemed worthy of taking forward.

Recognizing a placebo’s intrinsic value as something that can improve pain, however, scientists are now investigating the placebo effect on the endogenous opioid system. This makes sense because we know cognitive factors — our thoughts, beliefs, and expectations — can affect our physical and emotional well-being by activating the endogenous opioid system. We also recognize that the effect of any treatment, placebo or “real,” may be affected by the meaning we attach to it, in addition to the physical property of the treatment itself.

Two important findings about placebos have become clearer over time. First, there is no single placebo effect; placebo effects are influenced by a multitude of factors at any given time, including expectations (positive or negative) about treatment. Second, these expectations, while intangible, are the product of subjective and physiological experiences that are wired into the brain’s pain-processing circuitry and can be modified over time. This means that far from just being a sham treatment, placebo is a legitimate tool in your pain toolbox.

Now let’s turn to the external tools. Keep in mind that these can change, or how we use them can change, as scientific understanding evolves. Here’s a simple example that involves a routine home remedy so common and widely accepted, you’ll be surprised to learn that it’s been at the center of a simmering debate for nearly fifty years — and counting.

You’ve probably heard of RICE — rest, ice, compression, and elevation — and may have even used it to treat a sprain, strained muscle, or painful bruise. For as long as I can remember, RICE was the recommended first response for treating acute tissue injury.

The concept of RICE dates back to 1978, when a sports medicine physician named Gabe Mirkin coined the term, which coaches and health care providers quickly adopted. At the time, conventional wisdom was that reducing inflammation, along with resting, would reduce pain and hasten healing. Slightly elevating an injury to decrease blood flow and applying gentle pressure presented no red flags medically, so the RICE treatment grew in popularity.

Whenever I had a mild injury, I used these steps too without ever giving it much thought. Recently, though, amid a flourishing debate, some newer candidates include PEACE (protect, elevate, avoid anti- inflammatories, compress, and educate); LOVE (load, optimism, vascu- larization, and exercise); and POLICE (protection, optimal loading, ice, compression, and elevation). Without going into all the differences — from vascularization (blood vessel formation) to gauging the proper load for an injured muscle — I’d just point out that the expanding conversation reflects that focus on tweaking health and medical approaches as new scientific findings emerge. What I see as most compelling is a loose but well-reasoned growing consensus that suggests the better option is to replace RICE with MEAT, which stands for movement, exercise, analgesia, and treatment.

Here’s why. The downside of RICE is that it tamps down inflammation.
As you’ve read in previous chapters, some level of inflammation is necessary to activate healing processes and reduce the chance of developing chronic pain. While dialing down inflammation may initially ease pain, it also can delay or inhibit long-term tissue healing. The lesson is a critically important one when it comes to pain: let the body take care of itself as naturally as possible. Given what we now know, unless you have a fractured bone or can’t bear weight, RICE should no longer be the blanket recommendation for pain management.

Instead, the emphasis is now on these four steps:

Movement: Mild movement or exercise improves blood flow and circula- tion of healing agents to the injured area. It stimulates muscle, tendons, ligaments, cartilage, and other tissue, whereas stagnation can stall healing and lead to continuing pain.

Exercise: This component is meant to kick in once the pain has lessened.
For a muscle injury, this would involve gentle moves designed to slowly restore function and flexibility. For other types of bruised or swollen soft tissue, for example, from surgery or trauma, mild exercise further improves circulation.

Analgesia: Cautious use of pain relievers if necessary, as well as the use of natural options such as turmeric or capsaicin instead of anti-inflammatories, which may inhibit healing for the reasons already described. Also consider topical anesthetics and analgesic patches, or mild transcutaneous neurostimulation such as the TENS device, which applies a low-voltage current to the skin.

Treatment: The final component of MEAT refers to the range of tailored early treatment through various therapeutic approaches. These might include physical therapy, massage, acupuncture or other “dry needling” (solid needles containing no medication), myofascial release (and other techniques using targeted massage to release tension in a specific muscle area), joint mobilization (to improve range of motion), as well as use of ice and heat.

Heat and cold therapy both can help relieve pain, though they work in different ways and are best for different situations.

Cold therapy is best for short-term pain, applied within the first seventy-two hours to counter swelling. Keep in mind that while cold temperature slows blood flow, which can help reduce pain from sprains, strains, and other acute injuries, it may also decrease inflammation, slow healing, and increase the likelihood of chronic pain. Regular cold-water plunges have gained a popular following in recent years, and some studies suggest that regular cold exposure through ice bathing or plunges may ease discomfort after intense workouts and help with stress regulation. These may not be the best options, however, for treating an injury. The practice continues to be the subject of debate because it may also carry risks for some people — in particular those with cardiovascular issues. The concern is something known as a cold shock response, which can lead to an increase in blood pressure and heart rate. Some may also hyperventilate, which can lead to fainting as well.

Heat therapy is best for long-standing muscle pain, stiffness, and chronic pain conditions. Because it boosts blood flow, which can help relax muscles and ease aching joints, heat therapy is often recommended before exercise or stretching or to ease morning stiffness. Applying low-level heat for a longer period, such as with heat wraps you can buy at the drugstore, may reduce stiffness and tension and increase flexibility. Just be sure to follow product directions.

Either way, don’t overdo it. When using a hot or cold pack, wrap it in a thin towel to protect your skin and apply it for no more than ten to twenty minutes to avoid skin damage. You can do this several times a day, but be sure to take breaks in between to let your skin and tissue recover. And stop using heat or cold therapy immediately if it worsens your pain or discomfort or if your skin reacts.

Neither MEAT nor RICE is all wrong or always right. But with a basic understanding of these points of difference, you’re better equipped to eval- uate your options. The bottom line is that a desire for a quick fix may slow your overall healing process; as a general rule, be conservative with initial interventions like these and pay attention to the way your body responds; let the body heal itself and intervene only when necessary.

Renewed urgency about extended use of aspirin and NSAIDs

Now let’s return to your home medicine cabinet and the nonprescription painkillers you probably keep on hand. If your everyday go-to for pain relief is aspirin or another NSAID (nonsteroidal anti-inflammatory drug), it’s time to take a fresh look at how you use it. We now have not just new information, but continued findings over time, that have renewed urgency about the serious risks NSAIDs present for some people, as well as the adverse effects of taking too much or taking them for too long.

NSAIDs provide predictable relief for so many routine aches and pains — arthritis flare-ups, headaches, fever, menstrual cramps, colds, flu — that it’s easy to lose track of how often you’re using them and how much you’re taking, and overlook their potential for toxic or other adverse effects. And because these drugs are sold over the counter, it often means you’re making a decision about medication without your physician’s guidance on how to avoid potential problems based on health conditions you may have or medications you may be taking. Keep in mind that these nonprescription medications were mostly intended for short-term use, so relying on them long term might put you at risk for complications.

Aspirin is a good example. For decades, aspirin has been used for primary prevention of atherosclerotic cardiovascular disease, which is heart disease from plaque buildup in the arteries. In light of recent trial data, however, that practice is now controversial. The risk of bleeding might simply be too high to justify the benefits of preventing heart disease in someone who’s otherwise healthy.

That is why in 2022, the US Preventive Services Task Force recommended that people over sixty years old should not take aspirin to pre- vent primary heart disease. Even for those aged forty to forty-nine who may have a lower bleeding risk, the benefit is still thought to be small. If you’ve already had heart problems or have a strong family history and no evidence of bleeding problems, your doctor may recommend a daily baby aspirin. But in general, many doctors have moved away from the practice.

Supplements: Considerations, caution, and careful use

People are turning increasingly to dietary supplements, seeking out substances they perceive as natural. Unfortunately, because there are very few good, randomized trials, it’s hard to find solid evidence of the benefits of this approach. Additionally, many of these “natural” supplements are unregulated, meaning there’s no guarantee that they’re safe or consistent. There may also be interactions with prescription medications you’re using or other health conditions the supplement could adversely affect. Still, even given the above caveats, I will name a few that are worth considering:

Coenzyme Q10 or C0Q10. There is evidence that this coenzyme can improve mitochondrial function within cells and also act as an anti- inflammatory. Given the way it works, it may be most beneficial when taken after intense activity or with the use of statin drugs — both of which can be associated with muscle aches. It may also effectively lower blood pressure.

Magnesium. Evidence exists that this simple mineral, which is found in all our bones, can help with pain, particularly in the lower back. By blocking calcium from entering cells, magnesium may reduce the excitability of your muscles, allowing them to relax and reduce spasm, especially after exercise.

Turmeric. Growing up in an Indian household, I’ve been eating turmeric since I was a kid. The active ingredient, curcumin, is thought to be a potent anti-inflammatory, particularly effective for osteoarthritis of the knees. Recently it has been recommended to help reduce the symptoms of irritable bowel syndrome. In recent lab experiments, however, turmeric inhibited some chemotherapy drugs from working against breast cancer cells and also increased the risk of kidney stones, so make sure to check with your doctor if there is a concern. And buy from a reputable source.
Turmeric is among spices that have recently been flagged as potentially being contaminated.

Willow bark. The active ingredient in willow bark is salicin, which is very similar to aspirin. It is broken down into salicylic acid, which helps decrease pain and fever, and like aspirin may have side effects such as upset stomach and bleeding problems. If you’re sensitive to aspirin, have kidney disease, or you’re taking a blood thinner (or planning surgery) check with your doctor.

As you consider these or any of the many other options for pain relief we’re about to explore, keep this in mind: pain relief isn’t just about physical relief; it is an integral part of a complex, dynamic healing process that involves every other system in your body.

One reason opiates have proven so destructive, especially when used as ongoing treatment for chronic pain, is that over time they corrupt those natural systems. In exchange for initial pain relief, they slowly disable processes essential for normal functioning and healing, and they can create new complications: constipation, nausea, slowed breathing, dizziness, depression, brain fog, and the obvious — dependence and addiction. All of these compromise healing and health, often prolong pain, and carry even greater health risks.

We’ve seen remarkable progress in pain management since the days when opioids and steroids were used to treat most pain maladies. For neuropathic pain, that shooting or burning sensation, we now have drugs such as gabapentin, a prescription medication originally developed as an anticonvulsant, which regulates how pain messages travel from the brain through the spinal cord and reduces the excitability of nerve cells in the brain. “Gaba” (sold under the brand names Horizint, Grayliese, and Neurontin) was approved for treatment of neuropathic pain about twenty years ago, but it is far from a perfect drug. A 2017 review concluded that while around half of those treated had objective pain relief, they also often experienced adverse effects such as dizziness, drowsiness, tiredness, headache, nausea and vomiting, memory loss, weight gain, coordination problems, and eye problems. The drug worked best for postherpetic neuralgia; evidence for other types of neuropathic pain was very limited.

We’ve also seen an uptick of interest in the use of antidepressants for pain, especially for chronic migraines and long-standing arthritic pain. It’s not entirely clear yet why they help relieve pain for some people. The fact that they increase serotonin, which can improve mood, might be one reason. It may also be that they affect the perception of pain, reducing the focus the person puts on it and thereby distracting them from it. What is clear is that these medications take a long time to work, sometimes up to several weeks, and even then, the patient may need regular dosage adjustments to minimize side effects. A 2021 systematic meta-review of thirty-three trials showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain with moderate certainty, osteoarthritis pain with low certainty, and sciatica with very low certainty on pain and disability scores.

A 2023 Cochrane network meta-analysis examining antidepressants across all chronic pain conditions concluded that after investigating twenty- five different antidepressants, “the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose.” There is also promising evidence for milnacipran, the study said, but higher-quality research is needed. “Evidence for all other antidepressants was low certainty.” Additionally, after randomized controlled trials excluded people with low mood, the review was unable to establish any beneficial effects of antidepressants for people with chronic pain. The review concluded that currently there is “no reliable evidence for the long-term efficacy of any anti-depressant.”

In people who suffer chronic pain, there’s emerging evidence that their sensory neurons are more excitable than usual and can therefore be more easily triggered. For that reason, there’s new interest in the use of sodium channel blockers, an established tool for quieting seizures, which are also caused by overexcited nerve cells in the brain. Novocaine, which dentists inject into the tissue they want to numb for a procedure, is one example of a sodium channel blocker. The goal has been to turn that into a pill that works for chronic pain conditions, and researchers are currently making progress on that front.

Just this year, the FDA approved the first new drug in a new class of non-opioid pain medicines, approved to treat moderate to severe acute pain in adults. The approval of Journavx (suzetrigine) marked the first approval of a new class of non-opioid pain relievers in more than two decades. While opioids primarily work by dulling sensations in the brain, the new drug, in fifty milligram oral tablets, is reported to reduce pain by targeting a pain-signaling pathway involving a specific sodium channel in the peripheral nervous system, before the pain signals reach the brain.
The efficacy of Journavx was evaluated in two randomized, double-blind, placebo-controlled trials of acute surgical pain, one following abdominoplasty and the other following bunionectomy. In addition to receiving the randomized treatment, all participants in the trials with inadequate pain control were permitted to use ibuprofen as needed as a “rescue” pain medication. Both trials demonstrated a statistically significant superior reduction in pain with Journavx compared to placebo, the FDA said in announcing the approval.

The discovery of this drug has a fascinating backstory. Nearly twenty-five years ago, researchers learned about a family of fire walkers in Pakistan. They could walk on hot coals without flinching. Importantly, they felt the coals on their feet and even knew they were hot, but it was the specific sensation of pain they weren’t feeling. It wasn’t that their feet were numb, given that the nerves responsible for heat and touch seemed unaffected. Rather it was just the pain-conducting nerves that were affected. That observation led to a quarter-century investigation, the identification of a gene unique to this family, and ultimately helped inspire the development of the new medication.

Medical interventions and medication management

Following are some of the many available options for pain relief and management: