Integrative Medicine

8 Exciting Therapies for Natural Pain Relief

By Kim Crawford, M.D. Last updated: April 21, 2021
8 Exciting Therapies for Natural Pain Relief

Exciting New Therapies for Natural Pain Relief

In this article I review some of the basics of pain relief you might have learned in health class, including all the ways to increase your natural painkillers: your endorphins, enkephalins, and endogenous cannabinoids (some of this might be familiar too). I also touch on some integrative, supplement-type methods you can track down on the internet by yourself and will finish by reviewing exciting and new forms of natural pain relief available only through qualified Functional medicine doctors (not on the black market please!).

I will discuss:

  • Most common natural therapies
  • How to increase endorphins
  • Cold for natural pain relief
  • Helpful herbals and supplements for natural pain relief
  • Cannabinoids
  • Low-dose Naltrexone
  • Selank Peptide
  • Semax Peptide
  • DSIP Peptide
  • Concluding remarks
Common Natural Pain Relief Therapies 

But a Word About Diet First

One of the first things I do with new patients is to ask them to alter their diet. Most people aren’t aware how inflammatory, and therefore pain-inducing, some of the foods they typically eat can be. The absolutely most anti-inflammatory diet is my autoimmune protocol diet. Avoiding fast and processed foods, grains (especially gluten), seed oils, dairy, and other lectins such as peppers, eggplants or white potatoes, is totally game-changing. When it comes to natural pain relief, an anti-inflammatory diet is Job #1.

Below are some other basics, which may or may not be helpful, depending where you are on your own “pain journey.” Meaning, hang on. If you are farther along on this road, there are additional and exciting compounded alternatives you have not yet heard of that I will discuss.

Fairly Well-Known Methods of Pain Relief

Many of us know the comfort of a warm bath (‘hot soak’) and a wet, dry, or far-infrared sauna. A simple, long, hot shower helps muscular or non-inflammatory joint pain when we’re stiff and achy. Massage therapy is proven to improve lymph drainage and increase endorphin levels.

Remember that endorphins are your endogenous painkillers, produced (mainly) by the posterior pituitary gland. Although there is speculation about the relative significance of endogenous cannabinoids and enkephalins, endorphins are still considered the #1 endogenous pain reliever.

For most people, the following endorphin boosting methods will bring some temporary pain relief. Unfortunately, these methods don’t work well (if at all) for patients with some pituitary tumors or active mold and mycotoxin illness. But, as someone who treats a lot of mold illness, let me tell you that the posterior pituitary does “bounce back” and these methods will indeed work again.

Increasing your Natural Pain Killers: Your Endorphins

Massage: Yes, I am repeating myself here, but if you can afford it a massage is not just a feel-good activity. A nice, firm, muscle-kneading massage increases endorphins for several hours, adding yet another layer to pain relief.

Exercise: Most of you know that exercise increases endorphins. But do you know that a “runners high” is now thought to be (at least partially) due to endogenous cannabinoids, not to endorphins? And there is definitely something to be said for group fitness activities. A clinical study found that athletes who rowed together could tolerate two times the pain compared to athletes who rowed alone.

Laughter: Laugh out loud and your body releases endorphins! Read emailed jokes. Watch comedy specials. Laugh every single day as if your health depends on it.

Eat Your Favorite Foods: If you love it on your tastebuds, you will produce endorphins. And Yes, even healthy foods can be delicious, so keep this in mind when you’re looking for an endorphin rush.

Do You Like Dark Chocolate? Dark chocolate contains much more healthy flavonoids – and far less sugar – than milk chocolate, but a couple of squares of either will give your endorphins a boost. Cocoa also contains a mood-boosting substance called phenethylamine. It is the phenethylamine in the cocoa that gives your body an endorphin boost. Interestingly, however, phenylethylamine supplements do not have the same effect.

Eat Hot Peppers: If you have a strong, healed gut and can eat the occasional “nightshade” (a lectin), these really can give you an endorphin rush. Your body senses “heat stress” and responds the same way it responds to pain – by producing endorphins.

Listen to Music: Enjoy the music you love. But did you know that your brain produces even more endorphins when you take part in creating music. If you are not a trained musician…then hum to, or sing along with, or even dance, with abandon, to your favorite tunes.

Have Sex: As you might predict, sex releases a flood of endorphins as well as other feel-good brain chemicals.

Try Acupuncture: The minor amount of pain caused by acupuncture needles sends a message to the brain, which then responds with the release of endorphins. Less data is documented regarding the placement of needles, but logically, of course, there is “something to it.”

Get Some Sunlight: A mere 5 to 10 minutes of direct sunlight will increase mitochondrial ATP as well as endorphins. And if it gets too hot for you, some cold therapy afterwards might just feel great!

Cold for Natural Pain Relief

Now that I’ve discussed endorphins, let me add another method to my list. Any sort of cold or cryo-therapy will cause your posterior pituitary to release endorphins, but referring back to the “stress” concept, when your body experiences stress or pain, the brain releases endorphins.

There is quite an accumulation of positive data on everything from winter swimming to ice baths regarding pain relief, reduction of inflammation and, Yes, even endorphin production. How to bring on the cold? If you’re up north and it is winter, go outside in shorts and a T-shirt. If not, try an ice vest, or multiple gel cold packs, or a brief ice bath, or even a cryotherapy tank. Cold works, and not just for localized pain due to injuries as most people think.

Several inflammatory cytokines, including TNF-alpha and IL-6 (both of autoimmune disease fame), will increase pain. In clinical studies, levels of TNF-alpha, IL-6, and a host of other inflammatory cytokines have been shown to be epi-genetically down-regulated systemically with the use of cold packs.

Herbals, Supplements and Integratives for Natural Pain Relief Backed by Science

Curcumin suppresses inflammation, which is a root causes of all diseases. Curcumin is the most potent of the three curcuminoids found in the spice turmeric. It suppresses pain by decreasing inflammation. It has more mechanisms of action than non-steroidal anti-inflammatory medications such as ibuprofen, and even more than steroids such as cortisone.

Curcumin is a safe inhibitor of the same pathways that the most complex drugs block: COX, COX-2, and LOX. In fact, curcumin inhibits the entire arachidonic acid cascade. In clinical studies, curcumin has worked as well as phenylbutazone and cortisone for osteoarthritis, rheumatoid arthritis, and post-operative inflammation. Studies show that curcumin inhibits the COX pathway better than indomethacin, a very strong mixed COX inhibitor that is still used to treat gouty arthritis.

Notably, curcumin has quite similar anti-inflammatory action as NSAIDs, but without the side effects. NSAIDs can have dangerous side-effects, and the COX-2 inhibitors are even required to include black-box warnings. Long-term NSAID usage causes leaky gut in just about 100% of people. Generally safe, even at doses up to 8,000 mg per day, Curcumin must be taken with meals, and under a doctor’s supervision if at doses exceeding 1-2 grams per day.

Fish Oil: There is a good deal of clinical evidence that fish oils are very anti-inflammatory and therefore pain-inhibiting. As an aside, when my patients have “the occasional headache or backache,” I ask them to take some curcumin and fish oil.

Capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) is an extract from hot chili peppers. It is a decent topical analgesic for a variety of painful conditions.

Devil’s Claw is a plant native to the African continent. Iridoid glycosides are the active ingredients. Several studies demonstrate relief with topical use for osteoarthritis.

Phytodolor is an herbal formulation containing alcoholic extracts of Populus tremula, Excelsior, and Solidago virgaurea. Studies show that it is often effective in various inflammatory arthritic disorders.

Glucosamine and Chondroitin Sulfate are the principal components of cartilage. There are conflicting studies on the combination of glucosamine and chondroitin, with some demonstrating a beneficial effect on arthritis pain. More recent studies find that chondroitin alone does not reduce joint pain. Therefore, the use of chondroitin has dropped off but there is better news regarding glucosamine.

Glucosamine for Arthritis: There have been 30 or so well-done studies examining the efficacy of glucosamine for joint pain. On review of all data comparing glucosamine to either NSAIDS or placebo, the glucosamine edges out the NSAIDS by a hair. Recent data shows the mechanism of action is via blocking lectins. While there haven’t been any good studies comparing glucosamine to the elimination of lectins in the diet, “it’s a very good thought.”

Cannabinoids: CBD and THC

People rarely realize that CBD is most plentiful in the hemp plant, which contains minimal THC, and that THC is found in the marijuana plant, where the concentration of CBD is more scarce. Both plants are cannabis plants, by the way.

There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics.

When we discuss the benefits of CBD, we’re talking about “whole hemp CBD” because “extracts” of CBD are relatively useless. Yes, check to see what you have. Medicinal THC, however, can be made in many forms, but the best benefits are found in those plants with more CBD, and the best pain relief is found in those formulations that include the other aforementioned ingredients such as the terpenes.

In a 2018 review article, multiple studies revealed mixed results. It appears that cannabinoids appear to be most effective in controlling neuropathic pain, medication-rebound headache, and chronic noncancer pain, but do not seem to offer any advantage over nonopioid analgesics for acute pain.

Something marijuana enthusiasts don’t mention is that THC-cannabinoid-based analgesia has been linked to memory deficits and cognitive impairment. As with all mood-altering substances, we must be careful of our usage, dosing, and (IMHO) brain health protection, so that we do not experience any negative effects on our most important organ: our brain.

Meanwhile, animal studies demonstrate that whole hemp CBD oil increases endorphins. This has particular implications for patients with chronic pain syndromes such as fibromyalgia, CIRS pain due to EDS (endorphin deficiency syndrome), and neuropathies. An online patient survey by the U.S. National Pain Foundation of 1,300 fibromyalgia patients rated CBD as more effective than Cymbalta, or Lyrica.

If you have fibromyalgia, please read on, as there is much more “out there” for you. Here is the first thing you might want to try.

Low Dose Naltrexone

Naltrexone, was approved in 1984 by the FDA in a 50mg dose to help addicts wean off heroin. Naltrexone’s initial use was an opioid-antagonist drug used in large doses to block opioid receptors, and therefore the effects of opioid drugs.

Naltrexone was since studied in doses of 1-5 mg (hardly even a “drug” at those doses) and was found to perform other functions. It blocks the receptors of the opioid hormones in our brain and adrenal glands. Doing so produces the anti-pain endogenous chemicals called beta-endorphins and met-enkephalins, known as the opioid rebound effect. Blocking opioid receptors also upregulates something called opioid growth factor (OGF).

The mechanism of action of pain relief via OGF is fairly simple. By up-regulation of OGF via the temporary blockade of opioid receptors, you will see an increase in circulating endorphins and enkephalins via reduction of the inflammatory response. LDN is used not only for pain relief, but also to treat many autoimmune diseases; notably Crohn’s disease via different mechanisms of action. In addition, LDN is neuroprotective via the inhibition of microglial activation. But it is in cancer research where the really promising data is being seen, where OGF is identified as an angiogenesis blocker which then suppresses the growth of many types of cancer.

Review of LDN for pain 2020

Eight articles were ultimately selected for evaluation, after hundreds of reports of benefits were identified. Six studies included data on fibromyalgia, two studies included data on chronic regional pain syndrome, and one study included patients with multiple diagnoses, including interstitial cystitis, fibromyalgia, and chronic pelvic pain. The primary outcome of all of the studies was absolute pain intensity reduction. The writers of this review concluded that “Low-dose naltrexone provides an alternative in medical management of chronic pain disorders as a novel anti-inflammatory and immunomodulator.”

Before I move on to the last three new and novel pain therapies, I want to do a quick review of peptides, in case this is your first time hearing about them. Peptides are not “drugs,” because they are recognized by our bodies as “self-produced,” much like bioidentical hormones. Peptides are short segments of amino acids, usually comprised of between two and fifty amino acids.

The peptides we use in functional medicine are derived from human secretions and, being bioidentical, there are no “drug side effects.” There are many excellent peptides that are utilized for various benefits in functional and integrative medicine, but three in particular are used in various forms and combinations for the treatment of pain. They are:

Heptapeptide Selank: (Thr-Lys-Pro-Arg-Pro-Gly-Pro)

Numerous clinical studies have shown that Selank has strong anti-anxiety as well as neuroprotective effects. The clinical effects of Selank are similar to those of anti-anxiety medications such as benzodiazepines, which enhance the activity of the calming neurotransmitter, GABA. This suggests that the molecular mechanism of action of Selank also arises from its ability to enhance GABA’s activity on its receptors. This is supported by the strong positive correlation – in several clinical trials – between the changes in the expression of 45 genes one hour after Selank or GABA is given. Additionally, there is the data that, across-the-board, anxiety increases the perception of pain.

Here is some insight into why this may be true. Examination of patients with various forms of anxiety demonstrates a considerable shortening of enkephalin half-life. Selank dose dependently inhibits enzymatic hydrolysis of plasma enkephalins. Selank has been found to be a potent enkephalinase inhibitor. In other words, the enzyme that destroys the enkephalins is blocked by Selank, which has been proven to reduce anxiety.

Study results suggest that high efficiency of Selank in the therapy of anxiety and phobic disorders is due to its ability to inhibit enkephalin hydrolysis. A very nice side effect of this is that higher enkephalin levels will reduce pain. Ongoing studies suggest that Selank may additionally act via other brain chemical systems such as those that control dopamine and serotonin. Meanwhile, the data regarding these two systems is strong for my next peptide, Semax.

Heptapeptide Semax: (Met-Glu-His-Phe-Pro-Gly-Pro)

Semax is considered a nootropic peptide due to its ability to increase BDNF-brain derived neurotrophic factor. It has the same, and perhaps more pronounced effect, as Selank on enkephalinase, leading to increased levels of enkephalins. In addition, several studies demonstrate its ability to cause the brain to release both serotonin and dopamine, enhancing feelings of well-being, which will also decrease the perception of pain. It is being increasingly recognized as a fairly decent analgesic, despite the paucity of human clinical trials.

DSIP: (Trp‐‐‐Ala‐Gly‐Gly‐Asp‐Ala‐Ser‐‐‐Gly‐Glu)

Delta sleep-inducing peptide (DSIP) has potent analgesic activity in mice. DSIP may play an important role in pain regulation in the central nervous system, but it currently is primarily used for severe insomnia in humans. Research findings in humans are yet sparse, but in a study of seven patients with migraines and vasomotor headaches, this peptide (administered for 5 consecutive days) significantly lowered the perceived pain levels of six of the seven. Additionally, as an “incidental finding,” mood was elevated in all seven subjects.

DSIP does not appear to have binding activity to any subtype of opioid receptors. Animal studies show that DSIP stimulates the release of met-enkephalins. It might also then stimulate a stronger binding effect of those endogenous pain relievers to opioid receptors. More research is obviously needed, but for those with sleep and pain issues it is a great add-on.

Additional Comments

If you are looking to ‘go it alone’ for pain relief, know that there is some data on DL-phenylalanine regarding inhibition of enkephalinase, that you can buy liposomal GABA preparations to decrease anxiety, and that you can purchase 5-HTP supplements to augment serotonin levels – all of this, in addition to the endorphin-enhancing behaviors and the use of ‘cold’ and exercise. Remember that exercise probably not only releases endorphins, but it probably also increases levels of endogenous cannabinoids.

What you do not want to do, however, is increase your use of over-the-counter drugs for pain. Acetaminophen is toxic for your liver (and somewhat so for your gut), and NSAIDs such as Motrin and Aleve are uber-toxic to your kidneys and gut and, in fact, cause many cases of leaky gut, which then leads to all sorts of other issues.

Get some help for pain that does not respond to some of the natural things I have written about here. My last word of advice: Avoid Black Market Sources of Peptides and LDN, as you simply cannot know what you will be getting.



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