The Dirty Little Secret about Chronic Pain

Did you know that Americans experience chronic pain at three times the rate of the Irish? And that the US ranks the highest in chronic pain in the world, edging out Morocco and Bangladesh? The reason for this unsettling reality may anger you but 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. When pain occurs, they rush along the nervous system highway to park in a NK1 receptor and relay the message to the brain, “Hey, that hurts.”

Pain relief medications such as NSAIDs, Acetaminophen, Menthol, and Lidocaine are administered to alleviate this discomfort through various mechanisms. NSAIDs reduce the production of 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 from pain signals.

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 for a headache to lose efficacy, necessitating increased dosages or stronger alternatives.

Increased Substance P Levels Can Lead to Heart Failure

Recent studies have indicated that excessive levels of Substance P are a factor in heart failure, contributing to long-term damage and maladaptive remodeling of the heart’s structure and function. It’s no surprise that the United States ranks highest globally in consumption of painkillers while also facing the highest rates of chronic pain and heart disease.

The Elevated Substance P Spiral

“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.” ²

Recent studies reveal that high levels of menthol use increase colon disorders, including IBD (inflammatory bowel disease) and colitis. Elevated Substance P can increase hypertension. Additionally, elevated levels have been associated with many diseases: cancer; sickle cell crisis; major depression and related disorders; fibromyalgia; rheumatological conditions; and infections such as HIV/AIDS and respiratory syncytial virus.

Is Topical Pain Relief a Good Solution?

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%. This shift, has led to increasingly potent formulations despite growing evidence of adverse effects. A study published in *Frontiers in Pharmacology* highlighted the prevalence of high-menthol products, with concentrations exceeding 10% becoming increasingly common in the market. This trend reflects a shift towards more potent formulations, despite mounting evidence of adverse effects.

The Unsurprising Dirty Little Secret

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 Real Time Solution

In 1998, the creators of Real Time Pain Relief dedicated themselves to developing products that incorporated nature’s ingredients. Additionally, they do not use menthol at a concentration greater than 2% in their products, safeguarding the body against excessive production of Substance P.

Now, 27 years later, Real Time Pain Relief is the only top-15 over-the-counter 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. To learn more about our unique formulation strategy and why Menthol levels matter, Click Here.

References

1. "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.
2. Effects of the Neuropeptide Substance P on Sleep, Mood, and Neuroendocrine Measures in Healthy Young Men. Nature Article.
3. TRPM8 inhibits substance P release from primary sensory neurons via PKA/GSK-3beta to protect colonic epithelium in colitis. Nature Article.
4. Neurological Disorders, Hypertension. PMC Article.
5. Hypothalamic Substance P Release. AHA Journals.
6. Mantyh CR, Gates TS, Zimmerman RP, Welton ML, Passaro EP, Vigna SR, et al. (May 1988). "Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease." *Proceedings of the National Academy of Sciences of the United States of America*. DOI.
7. Fehder WP, Sachs J, Uvaydova M, Douglas SD (1997). "Substance P as an immune modulator of anxiety." *Neuroimmunomodulation*. DOI.
8. Geracioti TD, Carpenter LL, Owens MJ, Baker DG, Ekhator NN, Horn PS, et al. (Apr 2006). "Elevated cerebrospinal fluid substance P concentrations in posttraumatic stress disorder and major depression." *The American Journal of Psychiatry*. DOI.
9. Schwarz MJ, Ackenheil M (Mar 2002). "The role of substance P in depression: therapeutic implications." *Dialogues in Clinical Neuroscience*. DOI.
10. Rupniak NM (May 2002). "New insights into the antidepressant actions of substance P (NK1 receptor) antagonists." *Canadian Journal of Physiology and Pharmacology*. DOI.
11. Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (Jan 1988). "Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis." *Pain*. DOI.
12. Anichini M, Cesaretti S, Lepori M, Maddali Bongi S, Maresca M, Zoppi M (Jan 1997). "Substance P in the serum of patients with rheumatoid arthritis." *Revue du Rhumatisme*. PMID.
13. Douglas SD, Ho WZ, Gettes DR, Cnaan A, Zhao H, Leserman J, et al. (Oct 2001). "Elevated substance P levels in HIV-infected men." *AIDS*. DOI.
14. Palma C, Maggi CA (2000). "The role of tachykinins via NK1 receptors in progression of human gliomas." *Life Sciences*. DOI.
15. Singh D, Joshi DD, Hameed M, Qian J, Gascón P, Maloof PB, et al. (Jan 2000). "Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis." *Proceedings of the National Academy of Sciences of the United States of America*. DOI.