Pain Brain: Chronic Pain Drives Cognitive Decline

A recent study of data from more than 19,000 people showed that those who experience multiple sites of chronic pain are more likely to show hippocampal atrophy than those who are pain-free. The brain changes correlated with cognitive decline. (Image: Master1305/Shutterstock)

A massive new study of data from over 19,000 individuals shows that chronic pain is associated with loss of hippocampal volume and increased risk of dementia.

Compared with pain-free control subjects, those who had five or more areas of chronic pain showed neurological changes equivalent to eight years of excess brain aging (Zhao W, et al. PNAS. 2023). Simply put, the more regions of chronic pain people experience, the greater their risk of neurocognitive abnormalities.

“Our results suggested that cognitive decline and hippocampal atrophy interact biologically and may underlie the increased risk of dementia associated with multi-site chronic pain (MCP),” write Zhao and colleagues, based at the CAS Key Laboratory of Mental Health, Chinese Academy of Sciences, Beijing.

Zhao’s team used data from the UK Biobank, concentrating specifically on files from more than 19,000 individuals who’d undergone brain scans. The chronic pain problems in this large cohort were the result of a wide variety of causes, including arthritis, cancer, and low back pain.

Regardless of the specific causes, the brain impact of chronic pain was consistent.

“We found that individuals with MCP were associated with significantly higher dementia risk, broader and faster cognitive impairment, and greater hippocampal atrophy than both pain-free (PF) individuals and those with single-site chronic pain (SCP),” the authors note.

The impact of chronic pain on hippocampal volume and dementia risk correlated strongly with number of coexistent chronic pain sites, and the observed hippocampal atrophy was associated with measurable declines in fluid intelligence.

“Our results suggested that cognitive decline and hippocampal atrophy interact biologically and may underlie the increased risk of dementia associated with multi-site chronic pain (MCP)”

Wenhui Zhao, Institute of Psychology, Chinese Academy of Sciences, Beijing

In other words, constant pain in multiple anatomical sites leads to detrimental brain changes and impairs cognitive function. 

One in Five

These findings should prompt physicians in this country to sit up and pay attention.

Why? Because chronic pain is a major issue, affecting anywhere from 20% to 33% of all US adults, according to the Centers for Disease Control and Prevention.

In its April 14, 2023 edition of Mortality and Morbidity Weekly Report, the CDC estimated that fully one in five adults– approximately 20.9%, or 51.6 million people—experienced chronic pain in 2021, with 6.9% experiencing intense pain that limited daily activities.  

Those numbers are telling us something: conventional medicine, with its limited tool kit for managing pain, is not doing a very good job.

Most physicians rely on NSAIDs, acetaminophen, antiepileptic drugs, and serotonin/dopamine agents when treating people who live with chronic pain. Or they refer these patients out for surgery. The stats from the CDC and other sources show us clearly that this isn’t working.  And in light of the Zhao study, our system’s failure to properly address chronic pain has long term negative implications for cognitive health.

This article will review three key areas:

  1. A quick overview on how we can do better in eliminating pain
  2. Key tools for preventing dementia in general
  3. Use of low-dose naltrexone (LDN) to prevent pain-induced dementia

Secrets to Pain Relief

People do best with a comprehensive approach to pain management. This means addressing:

  1. The biochemistry of pain, via diet and nutrient interventions, herbs, and in some cases, prescription medications
  2. The biophysics of pain, via Frequency Specific Microcurrent therapy, acupuncture, and energy medicine
  3. The structural components of pain, via osteopathy, myofascial release, and chiropractic
  4. Mind/body/spirit aspects of pain, via techniques to release old emotions stored in muscles and the brain, and by eliminating things that are a “pain in the back” (or even lower!)

We will focus here on the biochemistry of pain relief, and dementia prevention.

Why Do We Have Pain?

The first step in eliminating pain is to realize that pain is not meant to be an enemy. Rather, it is like the warning light on a car’s dashboard telling us that something needs attention.

(Image: Passakorn vejchayachai/ Shutterstock)

When someone’s “oil light” goes on, in the form of a chronic pain, the standard medical response is to prescribe a drug or undertake a surgical procedure to make the warning signal disappear. And then, when the patient’s “motor” burns out, they think it was just coincidence.

But what if, instead, we treated the flashing oil light by actually adding oil? This works wonderfully!

What is Pain Asking For?

There are several pain-associated biochemical warning lights that are asking for different things. The most common ones are:

  • Low tissue energy: When muscles don’t have enough energy, they get locked into shortened positions, causing pain. It takes more energy for a muscle to relax, than to contract. This may seem counterintuitive, but consider how your muscles feel after a heavy workout. They don’t go loose and limp, rather they become tight. Chronic low tissue energy causes myofascial pain, and this is present in most cases of chronic pain, even if it is not the original cause of the pain.
  • Inflammation or immune imbalance: This is generally present in all conditions that end in “-itis,” such as arthritis. It is also present in many autoimmune illnesses. For arthritis, the herbal mixture Curaphen was as effective as Celexicob in head-on studies. Glucosamine and chondroitin was also highly effective, likely by feeding the joints the substrates they need to build and maintain cartilage.
  • Nerve pain: Interestingly, this is associated with uncontrolled firing of pacemaker-like cells, which then also deplete energy. Common triggers include nutritional deficiencies, low cellular energy from diabetes, fibromyalgia or hypothyroidism, and infections. Lipoic acid, 300 mg, twice daily and Acetyl-L-carnitine, 1000 mg, can be helpful in mitigating nerve pain, though it usually takes at least three months of regular use.
  • Central or brain pain: This is triggered by most other types of chronic pain, and it is associated with microglial activation (discussed below). Shutting down the microglial activation with low-dose naltrexone or other treatments can be very beneficial.
  • Sympathetically Maintained Pain/Complex Regional Pain Syndrome (CRPS): According to the International Association for the Study of Pain, sympathetically maintained pain is, “a type of pain that is maintained by sympathetic efferent innervation or by circulating catecholamines.” It can occur by itself or in conjunction with other types of pain. CRPS, formerly called “Reflex Sympathetic Dystrophy” is one form of it. This can be extremely debilitating. Management of CRPS is beyond the scope of this article but suffice to say the condition is now treatable. Feel free to email me at for a CRPS information sheet outlining my approach.

The CDC estimated that fully one in five adults experienced chronic pain in 2021. The numbers are telling us something: conventional medicine, with its limited tool kit for managing pain, is not doing a very good job.

Basics for Pain Relief

In general, when treating chronic pain, I start with general nutritional and herbal support.

Especially important is to ensure that the patient is getting high levels of B vitamins and magnesium to restore tissue energy. Then, omega-3s and herbs to balance inflammation. For the omega 3 support I use EurOmega 3, as one pill replaces seven large fish oil pills or capsules. I also then add Curaphen1-2 caps 3 x day. This pain relief formula contains a unique highly absorbable form of curcumin to balance cyclooxygenase (COX), boswellia to balance lipoxygenase (LOX), DL phenylalanine (DLPA) to increase endorphins, and nattokinase to mitigate inflammation and oxidative stress.

For arthritis or traumatic pain, I add a topical Comfrey (Symphytum) cream three times a day. Give this and the Curaphen for six weeks to see the full effect. These products can be combined, and also taken with other pain medications.

My books Pain-Free 1-2-3 and From Fatigued to Fantastic describe many helpful treatments tailored to various specific type of pain. Many of these can also be found in the free Cures A-Z phone app.

Basics of Dementia Prevention

It is remarkable how much research shows that the risk of dementia can be dramatically decreased via nutritional, botanical, and lifestyle interventions. And conventional medicine largely ignores all of this because the treatments are not expensive pharmaceuticals.

There are many things that can help. Here are some basics, organized around the mnemonic “MIND”:

METABOLIC- The key here is to optimize hormone levels with bioidentical hormone therapies. For example, thyroid hormone levels are strongly associated with risk of dementia. But there are gender differences in how this relationship plays out. In women, low-normal thyroid levels are associated with a 240% higher risk of dementia. In men, borderline elevated thyroid levels raise dementia risk by 800%!

Testosterone levels also influence risk of dementia, with low testosterone increasing it while higher levels seem to be protective. A 50% increase in free testosterone in the bloodstream was associated with a 26% decrease in the risk of Alzheimer’s. Men who develop Alzheimer’s disease have about half the free testosterone in their bloodstreams as men who do not.

INFECTIONS- Always check for silent bladder infections. Also consider candida, if a patient is experiencing a lot of postnasal drip, throat clearing, or flatulence. Chronic infections are associated with increased risk of dementia.

NUTRITIONAL Support- Beyond the basics of a healthy plant-rich diet, and the support of a good multivitamin, it is important to optimize folate, B12, other B vitamins, and Vitamin D.

When working with chronic pain patients, always check the B12 level. You want to keep that over 540 ng/L. Also look at the homocysteine level. Ideally, that should be under 9 µmol/L. The value of B vitamins in preventing dementia have been shown in a number of studies. For example, in the 2012 VITACOG study, people with mild cognitive impairment who took a daily combination of 0.8 mg folic acid, 0.5 mg vitamin B12, and 20 mg vitamin B6 showed markedly slower rates of cognitive decline and less brain atrophy than those assigned to the placebo group.

VITAMIN D is also very important, as was shown in a prospective study of over 12,000 individuals published earlier this year. Researchers at the University of Calgary found that, “Across all formulations, vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure.”

In the population as a whole, taking vitamin D was associated with a 40% lower incidence of dementia. The effect was significantly stronger in females versus males. It was also greater in those who had normal cognition at baseline compared with those who already had some degree of cognitive impairment.

Likewise, the protective effect seemed stronger in non-carriers of the apolipoprotein E ε4 allele versus carriers of this risk factor.

Be careful with iron, especially in carriers of the apolipoprotein E ε4 allele. According to researchers at the University of Melbourne, the presence of this gene tends to elevate ferritin levels in cerebrospinal fluid, and this is associated with declines in cognitive performance and increased risk of developing Alzheimer’s disease.

Do not supplement with iron if someone’s ferritin level is over 60 µg/L.

Curcumin (turmeric), a culinary favorite, appears to be neuroprotective. It is notable that the prevalence of Alzheimer’s in India—where curcumin is a dietary mainstay– is 70% lower than in the US. Curcumin also shows promise in many neurodegenerative conditions, including Parkinson’s.

Supplementation with curcumin makes sense for people at increased risk of cognitive decline. But this is one herb for which the form and brand really matter. I recommend a highly absorbable form of Curcumin called CuraPro, 750 mg, twice daily.

Be Cautious with Meds

Yes, pharmaceuticals are sometimes necessary for prevention or treatment of serious illnesses. There’s no question that drugs to control blood pressure, especially beta blockers and ACE inhibitors, can be protective for the brain in patients who have hypertension.

But it is equally important that we get our patients off unneeded or harmful drugs as often as we can.

Avoid Proton Pump Inhibitors:  In a 2016 study of over 73,000 elderly individuals, taking a PPI such as omeprazole and pantoprazole was associated with a 44% increase in dementia risk. Famotidine, an H2 receptor antagonist, does not seem to carry a similar risk.

Avoid Anticholinergic Drugs: Diphenhydramine, tricyclic antidepressants, and incontinence drugs like oxybutynin and tolterodine are especially problematic. In a study of 451 older individuals, cognitively normal at baseline, the use of anticholinergic drugs markedly increased risk of brain atrophy and cognitive impairment. The risk increase begins with as little as 60 days’ exposure.

Low-Dose Naltrexone

As noted at the beginning of this article, chronic pain is associated with decreased brain volume and increased dementia risk.

I believe low-dose naltrexone (LDN)—an old and inexpensive therapy–could potentially prevent millions of cases of dementia by alleviating chronic pain. Why? Because LDN addresses one of the main drivers of both chronic pain and brain atrophy.

Numerous studies show that microglial activation is a common denominator between chronic pain, fibromyalgia, and shrinking brain size. Researchers now recognize that microglial activation could be a potential target for pain management.

Microglial cells can be viewed as the brains “gardeners.” Normally they are mild-mannered, and simply tend to the needs of brain cells. They provide a first line of immune defense, and they are constantly “weeding” the brain of damaged neurons or potentially problematic amyloid buildup. 

But when something goes amiss in the brain, such as a viral infection or a chronic pain problem, these mild-mannered gardeners can become overactive and they start damaging healthy brain tissue. This microglial activation contributes to brain shrinkage and decreased volume.

The remedy? LDN!

At doses of 3-5 mg per night, LDN turns off microglial activation. This approach was outlined in a 2019 paper by Diana Trofimovitch and Steven Baumrucker, who propose the off-label use of LDN to manage non-malignant pain. “When used in doses of 1 to 5 mg, it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation.”

LDN has been shown in numerous studies, and borne out by wide clinical experience, to help eliminate pain and other debilitating symptoms of chronic pain conditions. There is a high probability that by shutting down the microglial activation, it can also prevent the increased dementia risk associated with chronic pain (See Low-Dose NTX to Quell Chronic Pain & Lower Risk of Dementia)

For information on how to treat fibromyalgia, long Covid symptoms, and other chronic pain syndromes, feel free to email me at and ask for my free information sheets. Please let me know that you are a practitioner, so I can include the free treatment questionnaires and checklists.

For guidance on how to address each type of pain (e.g., arthritis, migraines, etc.) simply download the Cures A-Z smartphone app. This tool quickly reviews each of the most common health conditions and suggests the best natural and prescription therapies for them. It’s kind of like having my brain in your pocket – but less messy!


Jacob Teitelbaum, MD, is one of the most frequently quoted integrative medical authorities in the world. He is the author of several best-sellers, including From Fatigued to Fantastic!, the Beat Sugar Addiction Now! series, The Fatigue and Fibromyalgia Solution, and the popular free smartphone app Cures A-Z. He is the lead author of 4 studies on effective treatment for fibromyalgia and chronic fatigue syndrome. He earned his MD degree from Ohio State University, and recently celebrated his 50th year as a physician. Learn more at

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