Hot and cold without heat

Section 3 of 4

A bite of chilli feels hot and a peppermint feels cool, and all the while your mouth stays at the same temperature. Each molecule switches on a receptor that senses temperature.

Capsaicin and the heat receptor

Nerve endings in your mouth and skin carry a receptor called TRPV1. It is a channel: a protein with a pore through the thin, oily layer that wraps the cell, its membrane. Above about 43 °C, hot enough to start to hurt, the pore opens, charged ions flow into the nerve, and the nerve sends the message "hot".

Capsaicin, the molecule that makes chillies hot, fits a pocket in TRPV1 and opens the same pore at body temperature. Your brain gets the message it gets from real heat, so your mouth burns, and your face may go red and sweat as your body works to cool down.

Capsaicin, C₁₈H₂₇NO₃The hot molecule in chilli peppers. A benzene ring carrying an -OH group and an -OCH₃ group, as in vanillin, joined through a -CH₂- group and an amide link, -NH-CO-, to a long carbon chain with a C=C double bond and a branched end.OOOHNH
Capsaicin, C₁₈H₂₇NO₃. Its benzene ring carries an -⁠OH group and an -⁠OCH₃ group, arranged as in vanillin. The long carbon chain at the other end is non-polar.

Menthol and the cold receptor

A second channel, TRPM8, opens when your skin cools below about 25 °C, and the nerve sends the message "cold". (−)-⁠Menthol, from peppermint oil, fits TRPM8 and opens it at body temperature, so mint feels cool in your mouth.

(−)-menthol A skeletal formula: a ring of six carbon atoms. One ring carbon carries an -OH group, the next carries a three-carbon branch, and a carbon across the ring carries a methyl group. Wedges show which way each of the three groups points: the three stereocentres give menthol its hand. O H
(−)-⁠menthol, C₁₀H₂₀O, the hand in peppermint. Its three stereocentres are the ring carbons that carry the -⁠OH group, the three-carbon branch and the methyl group; the wedges show which way each group points.

TRPM8 is handed, and here the hand counts: people breathing in the vapour of each pure hand found that (−)-⁠menthol gave a stronger feeling of cold than (+)-⁠menthol. The two menthols smell alike, and the cold receptor tells them apart.

Two receptors that sense temperature
ReceptorOpened byMessage
TRPV1heat above about 43 °C, and capsaicinhot
TRPM8cool below about 25 °C, and (−)-⁠mentholcold

David Julius found TRPV1 in 1997 by searching for the receptor that capsaicin opens. In 2002 his team and Ardem Patapoutian's each used menthol to find TRPM8, and the two scientists shared the 2021 Nobel Prize in Physiology or Medicine.

Putting the fire out

Capsaicin's long carbon chain is non-polar, and only the part near its ring has groups that make hydrogen bonds. Water molecules hold on to each other and squeeze capsaicin out, the way they squeeze out oil, so a gulp of water carries very little of it away and the burn stays. Capsaicin dissolves well in oils, fats and ethanol. In a 2019 test in the United States, milk eased a chilli burn more than water did, and skimmed milk worked as well as whole milk, so something besides the fat helps: the milk proteins are the likely reason.

Quick check

Why does a gulp of cold water do little for a chilli burn?