The Truth About Chronic Pain

The Dirty Little Secret About Chronic Pain | Real Time Pain Relief

Chronic Pain & Substance P

The Dirty Little Secret About Chronic Pain

Chronic pain — a hidden epidemic in America: the US ranks highest in the world for chronic pain rates

America ranks #1 globally in chronic pain rates. Understanding why — and the role of Substance P — may change how you think about pain relief forever.

Why Are Americans in More Pain Than Anyone?

Americans experience chronic pain at three times the rate of the Irish — and the US ranks #1 globally in chronic pain, edging out Morocco and Bangladesh. The reason may anger you, but it likely won’t surprise you.

Pain is a complex experience, and understanding how our bodies handle pain can help us make smarter choices about how we treat it. From neurotransmitters to pain relievers, every decision matters in avoiding and eliminating chronic pain.

Substance P is a sensory neurotransmitter that contributes significantly to how we perceive pain. Unlike other neurotransmitters that modulate mood or muscle movement, Substance P is specifically involved in transmitting pain signals and amplifying the body’s inflammatory responses — making it a central player in chronic pain and sensitivity. These molecules function as sensory messengers distributed throughout the body, transmitting signals that alert the brain to potential pain.

The US by the Numbers

3× Higher Than Ireland

#1 in Chronic Pain Globally

#1 in Painkiller Consumption

#1 in Heart Disease

Pain Masking Increases Substance P

How Pain Relief Can Make Pain Worse

Substance P — the pain signal messenger: how this neuropeptide transmits and amplifies pain signals through the nervous system

Pain relief medications such as NSAIDs, Acetaminophen, Menthol, and Lidocaine are administered to alleviate discomfort through various mechanisms. NSAIDs reduce inflammatory chemicals that trigger Substance P release, while acetaminophen modulates pain signaling in the brain. Menthol and lidocaine work locally by desensitizing sensory nerves and preventing Substance P from binding to NK1 receptors, offering temporary relief.

While this can be beneficial in the short run, it initiates a problematic cycle. When the body experiences pain and the brain doesn’t get the message, the response is to create more Substance P to ensure the brain gets the message. Elevated levels of Substance P gradually lower our pain threshold, making us more sensitive to pain over time.

As more pain goes unrecognized due to masking treatments, greater amounts of Substance P are generated, contributing to chronic pain conditions. This is why, over time, it is typical for a medication that initially provided effective relief to lose efficacy — necessitating increased dosages or stronger alternatives.

The cycle in plain terms: Mask the pain → body produces more Substance P → pain threshold drops → you need more medication → repeat.

What Elevated Substance P Does to Your Body

Contributes to Heart Failure

Recent studies indicate that excessive Substance P is a factor in heart failure, contributing to long-term damage and maladaptive remodeling of the heart’s structure and function. It’s no coincidence the US leads globally in painkiller consumption and in chronic heart disease.

Behavioral & Neurological Effects

Research has demonstrated that elevated Substance P produces significant changes in mood, sleep parameters, and neuroendocrine measures in healthy individuals. High menthol use is also linked to increased colon disorders including IBD (inflammatory bowel disease) and colitis, as well as elevated hypertension.

Associated Chronic Conditions

Elevated Substance P levels have been associated with cancer, sickle cell crisis, major depression and related disorders, fibromyalgia, rheumatological conditions, and infections including HIV/AIDS and respiratory syncytial virus.

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“We have shown that infusion of Substance P has significant biological and behavioral effects in healthy young men as demonstrated by significant changes of mood, sleep parameters and neuroendocrine measures. These effects can be interpreted as evidence for a central arousing effect of Substance P.”

— Effects of the Neuropeptide Substance P on Sleep, Mood, and Neuroendocrine Measures in Healthy Young Men, Nature

The High-Menthol Problem

Twenty years ago, topical pain relievers were a safer alternative. However, as large pharmaceutical companies acquired many topical pain relief manufacturers, menthol levels have risen well over the 2% threshold — with many products now exceeding 10%. A study published in Frontiers in Pharmacology highlighted this trend, noting concentrations above 10% becoming increasingly common despite mounting evidence of adverse effects.

Are you surprised that Big Pharma, which controls most of the oral and topical painkillers in the US, is behind the chronic pain escalation? Is it a coincidence that this also contributes to the need for various prescription drugs for chronic pain, heart disease, high blood pressure, cancer, IBS, colitis, and more?

💡The United States ranks highest globally in consumption of painkillers while also facing the highest rates of chronic pain and heart disease.

High menthol levels — a double-edged sword: topical products exceeding 10% menthol increase Substance P production and worsen chronic pain over time

The Real Time Pain Relief Solution

In 1998, the creators of Real Time Pain Relief dedicated themselves to developing products that incorporated nature’s ingredients — with menthol at no more than 2% — safeguarding the body against excessive Substance P production.

27 years later, Real Time Pain Relief is the only top-15 OTC topical pain relief manufacturer in America that maintains a menthol content below 2% for all its products. Real Time Pain Relief’s commitment to balanced formulations and safe, effective relief makes it a standout choice. By prioritizing nature’s ingredients and avoiding harmful menthol levels, they’ve helped millions achieve real, lasting comfort.

Try Real Time Pain Relief Today Learn About Our Formulation Strategy

References

“Disease etiology appears to be critical when it comes to the role of substance P in the heart, and the bad side of substance P is seen in long-term non-ischemic myocardial remodeling and heart failure.” Substance P in Heart Failure: The Good and The Bad.
Effects of the Neuropeptide Substance P on Sleep, Mood, and Neuroendocrine Measures in Healthy Young Men. Nature Article.
TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis. Nature Article.
Neurological Disorders, Hypertension. PMC Article.
Hypothalamic Substance P Release. AHA Journals.
Mantyh CR, et al. (May 1988). “Receptor binding sites for substance P… are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease.” PNAS. DOI.
Fehder WP, et al. (1997). “Substance P as an immune modulator of anxiety.” Neuroimmunomodulation. DOI.
Geracioti TD, et al. (Apr 2006). “Elevated cerebrospinal fluid substance P concentrations in posttraumatic stress disorder and major depression.” American Journal of Psychiatry. DOI.
Schwarz MJ, Ackenheil M (Mar 2002). “The role of substance P in depression: therapeutic implications.” Dialogues in Clinical Neuroscience. DOI.
Rupniak NM (May 2002). “New insights into the antidepressant actions of substance P (NK1 receptor) antagonists.” Canadian Journal of Physiology and Pharmacology. DOI.
Værøy H, et al. (Jan 1988). “Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia.” Pain. DOI.
Anichini M, et al. (Jan 1997). “Substance P in the serum of patients with rheumatoid arthritis.” Revue du Rhumatisme. PMID.
Douglas SD, et al. (Oct 2001). “Elevated substance P levels in HIV-infected men.” AIDS. DOI.
Palma C, Maggi CA (2000). “The role of tachykinins via NK1 receptors in progression of human gliomas.” Life Sciences. DOI.
Singh D, et al. (Jan 2000). “Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells.” PNAS. DOI.

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