Re: What are the main functions of Methyl salicylate, Menthol and Camphor

Hi Brooke,

I'm sorry that it has taken so long to respond to your question, but I hope that this answer is still of use to you. Your question has some medical implications, but I am going to try and focus on the biochemical issues.

Methyl Salicylate (aka Methyl Salicylic Acid), Menthol and Camphor are all chemicals that were originally derived from plants, and which are used by plants to protect themselves from the unwanted attentions of animals (usually insects) by interfering with animal body chemistry. Methyl Salicylate is derived from Oil of Wintergreen, which I believe comes from Birch leaves. Menthol is derived from Mint, and Camphor (used in mothballs) is derived from a number of plants, including Peppermint, Eucaluptus, and Cedar. In some cases, Camphor is also called Menthol. In addition, all three of these compounds are toxic if administered in improper doses, especially for young children.

All three of these compounds have anaesthetic effects, and also have sensatory effects on the skin, as described below.

Methyl Salycilic Acid is related to Acetyl Salicylic Acid, a compound that is better known as Aspirin. The mode of action of Aspirin's anesthetic effects is described in the MadSci Archives (here and here). The mode of action of Methyl Salicylic Acid is likely very similar (if not identical) to that of Aspirin, and I suspect that any pain relief produced by the cream you describe is due to this Aspirin-like effect. In addition, Methyl Salicylic Acid seems to produce a warm sensation in the skin. When applied to the skin, the level of Methyl Salicylic Acid detectable in the blood seems to be dependent on the region of skin where the drug was applied, so its effects can be variable depending on where it is rubbed.

Menthol and Camphor both have topical anesthetic properties, but I suspect that they have been added to the cream for the effect that they have on the skin. The Menthol molecule can bind to and stimulate the TRPM8 receptor protein expressed by pain and temperature sensing neurons. This receptor produces a sensation of cold (and pain in extreme cases) when stimulated. You experience this when you taste mint, and I believe the cream you describe produces a cooling sensation too. Menthol's anesthetic properties might result from the blockage of voltage-operated sodium channels in pain-receptor neurons. In addition, Menthol seems to enhance the permeation of drugs into the skin, so it may enhance the update of Methyl Salicylic Acid. Menthol may also dilate blood vessels, increasing blood flow to the region (which could aid in the uptake of Methyl Salicylic Acid and reduce swelling in the region). I suspect that Camphor has similar effects (mild anesthetic, numbing of the skin, and perhaps enhanced uptake of other compounds).

While I am not 100% certain, I would guess that the Menthol and Camphor are just there so that you get the sensation that something is happening where you rubbed the cream on your skin (hot, cold and numb feelings). The pain relief most likely comes from the Methyl Salicylic Acid, in which case an Aspirin tablet might be just as good (especially since different doses of Methyl Salicylic Acid can be absorbed from different parts of the skin).

I hope this helps. I've provided some references below in case you have additional questions.

Methyl Salicylic Acid as an animal repellent

Clark L, Shivik J. Aerosolized essential oils and individual natural product compounds as brown treesnake repellents. Pest Managment Science 2002 Aug;58(8):775-83.

Methyl Salicylic Acid toxicity

Bell AJ, Duggin G Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis. Emerg Med (Fremantle). 2002 Jun;14(2):188-90.

Chan TY Ingestion of medicated oils by adults: the risk of severe salicylate poisoning is related to the packaging of these products. Hum Exp Toxicol. 2002 Apr;21(4):171-4.

Variation in dosage of Methyl Salicylic Acid depending on application site

Duncan EJ, Brown A, Lundy P, Sawyer TW, Hamilton M, Hill I, Conley JD. Site-specific percutaneous absorption of methyl salicylate and VX in domestic swine. Journal of Applied Toxicology 2002 May-Jun;22(3):141-8.

Menthol and skin permeability

Fujii M, Takeda Y, Yoshida M, Utoguchi N, Matsumoto M, Watanabe Y. Comparison of skin permeation enhancement by 3-l-menthoxypropane-1,2-diol and l-menthol: the permeation of indomethacin and antipyrine through Yucatan micropig skin and changes in infrared spectra and X-ray diffraction patterns of stratum corneum. International Journal of Pharmacology 2003 Jun 4;258(1-2):217-23.

Menthol and Cold Receptors

Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol Cell 2002 Mar 8;108(5):705-15.

Menthol and Anesthesia

Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwer M Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol European Journal of Anaesthesiology 2002 Aug;19(8):571-9.

Galeotti N, Ghelardini C, Mannelli L, Mazzanti G, Baghiroli L, Bartolini A Local anaesthetic activity of (+)- and (-)-menthol. Planta Med. 2001 Mar;67(2):174-6.