Topical Analgesics: A New Frontier for First-Line Pain Management

Persistent pain can have a significant impact on daily life and is the most common reason that patients seek medical care.¹ The CDC estimates that 51 million people in the United States experienced chronic pain in 2021, making effective treatment of the condition a public health imperative.²

Although many analgesics are known to be effective for pain treatment, opioids remain widely prescribed, with approximately 22% of patients with chronic pain using a prescription opioid in the previous 3 months, according to a study published in 2019³—despite the fact that prescribed opioids are involved in 40% of all opioid overdoses.⁴ Other popular oral treatments for chronic pain include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), but their long-term benefits are limited.

Topical analgesics can also be used to treat chronic pain.⁵ Available in OTC and prescription form, these products offer a more localized treatment option without the potential adverse events associated with other systemic chronic pain treatments. However, topical analgesics continue to be severely underutilized in the United States.

How Do Topical Analgesics Work?

Topical analgesics have long been studied and marketed for use, but their mechanisms of action are still not completely understood. Topical agents provide local relief by penetrating the outer layer of the epidermis, which is how they work to treat certain areas of pain. They have a low rate of systemic absorption compared with transdermal products, which are applied to the skin and exert their action by crossing into the bloodstream.⁵

Lidocaine, one of the most-used topical anesthetics for musculoskeletal and neuropathic pain management, is a lipid-soluble compound. It works by penetrating the permeability barrier on the skin’s outer layer and blocking impulse firing from nerve fibers.⁵

The 2021 discovery of skin receptors able to sense temperature and touch has made the use of nonopioid topical pain treatments more attractive. For example, the TRPV1 receptor is activated by heat to block pain receptors. Methyl salicylate, a topical medication applied to the skin via a patch, targets TRPV1 and inhibits certain enzymes of the arachidonic acid cascade pathway.⁵

Should Topical Analgesics Be the First Choice?

The efficacy of topical analgesics for acute and chronic pain treatment has been proven in several studies. In a pivotal 2010 trial, researchers evaluated a 10% methyl salicylate and 3% l-menthol patch. Researchers found that pain intensity was significantly reduced in patients who received the patch.⁶ This trial supported the first FDA approval for an OTC topical analgesic patch.

The safety of topical analgesics is also well documented. Topical agents are generally safer than systemic analgesics because of their reduced risk for adverse events and drug-drug interactions.⁵

A New Era of Pain Treatment

As evidence for the use of topical analgesics in pain treatment continues to increase, medical and professional societies have begun recommending their use. The American College of Rheumatology in 2019 published specialized guidelines for osteoarthritis treatment and recommended localized therapy when feasible.⁵ The Osteoarthritis Research Society International also published guidelines that year, strongly recommending topical NSAIDs for knee osteoarthritis. The organization further recommended topical NSAIDs for patients with gastrointestinal and/or cardiovascular comorbidities when nonselective NSAID use is restricted.⁵

In 2020, the American College of Physicians and the American Academy of Family Physicians published clinical practice guidelines for the management of acute pain from non–low back musculoskeletal injuries.⁵ Both organizations recommended topical NSAIDS, with or without menthol, as first-line therapies to improve pain, physical functioning, and patient satisfaction.

The clinical guidelines from the organizations, which prioritize the use of topical analgesics vs opioids, is aligned with recommendations from the CDC: In its clinical practice guidelines for prescribing opioids for pain, the agency says that use of nonopioid therapies should be maximized and that opioids should only be prescribed if the benefits outweigh the risks.9 The CDC recommends topical analgesics for localized neuropathic, musculoskeletal, and osteoarthritis pain.⁵

References

1. AMA Pain Care Task Force. Addressing obstacles to evidence-informed pain care. AMA J Ethics. 2020;22(8):E709-E717. doi:10.1001/amajethics.2020.709

2. Rikard SM, Strahan AE, Schmit KM, Guy GP Jr. Chronic pain among adults - United States, 2019-2021. MMWR Morb Mortal Wkly Rep. 2023;72(15):379-385. doi:10.15585/mmwr.mm7215a1

3. Dahlhamer JM, Connor EM, Bose J, Lucas JL, Zelaya CE. Prescription opioid use among adults with chronic pain: United States, 2019. Natl Health Stat Report. 2021;(162):1-9. doi:10.15620/cdc:107641

4. Hadland SE, Rivera-Aguirre A, Marshall BDL, Cerdá M. Association of pharmaceutical industry marketing of opioid products with mortality from opioid-related overdoses. JAMA Netw Open. 2019;2(1):e186007. doi:10.1001/jamanetworkopen.2018.6007

5. Gudin J, Mallick-Searle T. New science and a pragmatic approach to topical analgesics as first-line therapy. Pain Medicine News. May 19, 2022. Accessed July 7, 2023. https://www.painmedicinenews.com/topicalanalgesics

6. Higashi Y, Kiuchi T, Furuta K. Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin Ther. 2010;32(1):34-43. doi:10.1016/j.clinthera.2010.01.016Gudin JA, Brennan MJ, Harris ED, Hurwitz PL, Dietze DT,

7. Strader JD. Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational Optimizing Patient Experience and Response to Topical Analgesics study. J Pain Res. 2017;10:2341-2354. doi:10.2147/JPR.S143513

8. Gudin JA, Dietze DT, Hurwitz PL. Improvement of pain and function after use of a topical pain relieving patch: results of the RELIEF study. J Pain Res. 2020;13:1557-1568. doi:10.2147/JPR.S258883

9. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1