The Science Behind Topical Menthol and Camphor for Pain Relief

December 03, 2025

Close-up of glossy, dark green, oval leaves and one small dark berry on a branch of Camphor plant on light green background

Menthol and camphor are terpene compounds with a long history of therapeutic use including topically for pain.^1,2,3 Their molecular mechanisms of action, however, have only begun to be understood within the last couple of decades. They each belong to a class of analgesics known as counterirritants. Counterirritants have their effects by first activating and then desensitizing nociceptors in the skin.⁴

Menthol and camphor are able to penetrate the outer layer of the epidermis (stratum corneum) and interact with peripheral sensory neurons in the dermal-epidermal junction that extend close to the skin surface.⁵

Mechanism of Action

Counterirritants work by activating a subgroup of receptors within the superfamily of sensory neurons known as the transient receptor potential (TRP) ion channels. TRP receptors are found throughout the body in both sensory neurons and non-neuronal tissue. Menthol and camphor interact with subgroups within this superfamily: menthol activates transient receptor potential melastatin-8 (TRPM8) receptors, which are responsible for its cooling sensations,⁶ and camphor interacts with multiple TRP channels, including TRPV1 and TRPA1 channels. TRPV1 (transient receptor potential vanilloid 1) and TRPA1 (transient receptor potential ankyrin 1) receptors are involved in nociception and TRPV1 and TRPV3 are responsible for the warming sensations associated with camphor.⁷

Menthol produces a cooling sensation on the skin, while camphor can elicit warming and cooling sensations. In reality, skin temperature does not change, but the perception of cooling and warming occurs as a consequence of menthol or camphor interacting with TRP receptors. In effect, topical application of a counterirritant acts as an ongoing agonist at TRP receptor sites. Applied topically, camphor initially activates TRPV1, TRPV3, and TRPA1 receptors, which may lead to the release of neuropeptides such as substance P from sensory nerve endings, and this is followed by receptor desensitization that contributes to analgesic effects. Menthol primarily activates TRPM8 receptors that are associated with analgesic effects. Both of these pathways led to relief from the experience of both acute and inflammatory pain.^7,10,11

In sum, menthol and camphor provide similar effects through different pathways. Clinical studies demonstrate camphor follows gate control theory principles by creating competing sensory input, effectively "closing the gate" to pain transmission at the spinal cord level. The counterirritant mechanism involves initial nociceptor activation followed by rapid desensitization, creating mild irritation that masks deeper pain through sensory competition.^12,13 Clinical studies demonstrate menthol activates TRPM8 receptors in cold-sensitive sensory neurons, creating cooling sensations that provide analgesic effects through central inhibitory pathways.

Menthol

Menthol has analgesic effects on acute and inflammatory pain primarily by activating cold-sensitive TRPM8 receptors in the skin. It may also have additional analgesic effects by binding to kappa-opioid receptors.14Menthol has anesthetic properties as well, which may be mediated by interaction with GABA receptors.15 In addition to these mechanisms, menthol acts as a vasodilator. It dilates local blood vessels in the skin at the site of application, thereby improving blood flow to any areas of injury or inflammation.¹⁶

In a triple-blind, randomized, placebo-controlled, crossover study, cutaneous application of a 10% menthol oil was shown to provide sustained pain relief and to alleviate symptoms of nausea, vomiting, photophobia, and phonophobia in migraine patients. The menthol group had a higher percentage of participants reporting being pain free 2 hours after administration and a higher percentage of the group reporting being pain free at 24 and 48 hours post administration compared to placebo.¹⁷ 

In a triple-blind, randomized, placebo-controlled cross-over trial of carpal tunnel syndrome, topical application of a 4% menthol gel reduced pain intensity compared to placebo at 1, 2, and 3- hours post application to an extent that study authors recommended it should be considered as an alternative to analgesic drugs for the management of chronic and neuropathic pain in the workplace.¹⁸

In a "proof of concept" study without a placebo control, a 1% menthol cream was applied twice daily in patients with neuropathic pain related to cancer treatment. After 4-6 weeks of application, 82% of participants reported improvement in total Brief Pain Inventory scores along with improvements in walking ability and sensation.¹⁹

In a randomized clinical study examining the cooling effects of menthol, cooling effects were observed at concentrations of 0.5%, 4.6%, and 10.0%, although the most efficacious dose was at 4.6% concentration. ²⁰ The FDA has approved the use of menthol in over-the-counter products for topical analgesic use at concentrations ranging from 1.25-16% . ²¹

Camphor

Like menthol, camphor acts as a vasodilator and has been shown to improve blood circulation to the skin and muscles.  Clinical evidence supports camphor's effectiveness. It has been used to target a number of different issues including minor muscle aches and pains, inflammatory pain, and neuropathic pain.^22,23. Although placebo-controlled studies utilize camphor in combination with other key ingredients, the mechanisms of action for camphor's analgesic and anesthetic effects have been well-validated.^24,25 Camphor functions as a counterirritant that initially activates and then desensitizes pain receptors. It activates TRPV1, and then produces more rapid and complete desensitization compared to capsaicin,²⁶ while simultaneously inhibiting TRPA1 channels to provide pain-suppressing effects.²⁷ TRPV3 activation contributes to camphor's characteristic warming sensation.²⁸ Camphor's activation and then desensitization of pain receptors aligns with gate control theory whereby camphor creates competing sensory input that "closes the gate" to pain signals at the spinal cord level.^29,30 The FDA has approved camphor for topical use for pain relief and counter-irritant purposes (e.g., to provide relief related to insect bites, cold sores, poison ivy) in concentrations ranging from 3% to 11%.21

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References

Tags: Camphor Menthol Pain Science

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The Science Behind Topical Menthol and Camphor for Pain Relief

Mechanism of Action

Menthol

Camphor

References

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