Cannabis stops pain from hot chili peppers and hot mustard

Cannabinoids Desensitize Capsaicin and Mustard Oil Responses in Sensory Neurons via TRPA1 Activation Armen N. Akopian,1 Nikita B. Ruparel,1 Amol Patwardhan,1 and Kenneth M. Hargreaves1,2

Akopian et al. 28 5: 1064 — Journal of Neuroscience

Making Chili Powder by sporkist on Flickr

Making Chili Powder

(Thank you Sporkist on Flickr (under creative commons attribution license)

Chemicals in marijuana block pain generated by spicy food. Now researchers have figured out the mechanism. It has to do with channels in the cell membrane that let molecules go in or out.

I thought this paper was interesting on a number of levels:


First, the cannabinoid receptor. Blocking this receptor in the brain makes you not hungry. This was figured out by some scientists who, according to pharmaceutical folklore, were fairly stoned and had the munchies when they came up with the idea for an appetite suppressant which would block the same receptor activated by marijuana to make you hungry. This drug has not been approved by the FDA (briefing docs here), and is thought to make one depressed. No wonder. If smoking pot makes you care free and hungry, blocking the receptor not surprisingly makes you depressed and not hungry. IMO. Those darn cannabinoids, nothing but trouble.

Second, capsaicin. This molecule captures the yin and the yang of the universe. Part of the molecule causes pain. Part causes numbness. What a cosmologically humorous molecule. I lurve capsaicin.

Third, the testing methods included an RNA interfering molecule. The investigators used two ways to block the effects to see what would happen (in trying to find out the physiological pathway), including rnai. I thought this was pretty creative.

Cellular/Molecular
Cannabinoids Desensitize Capsaicin and Mustard Oil Responses in Sensory Neurons via TRPA1 Activation

Armen N. Akopian,1 Nikita B. Ruparel,1 Amol Patwardhan,1 and Kenneth M. Hargreaves1,2

Departments of 1Endodontics and 2Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229

Correspondence should be addressed to Armen N. Akopian, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Email: akopian@uthscsa.edu

Although the cannabinoid agonists R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate [WIN 55,212-2 (WIN)] and (R,S)-3-(2-iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole (AM1241) exert peripheral antihyperalgesia in inflammatory pain models, the mechanism for cannabinoid-induced inhibition of nociceptive sensory neurons has not been fully studied. Because TRPV1 and TRPA1 channels play important roles in controlling hyperalgesia in inflammatory pain models, we investigated their modulation by WIN and AM1241. The applications of WIN (>5 µM) and AM1241 (>30 µM) inhibit responses of sensory neurons to capsaicin and mustard oil. To determine potential mechanisms for the inhibition, we evaluated cannabinoid effects on nociceptors. WIN and AM1241 excite sensory neurons in a concentration-dependent manner via a nonselective Ca2+-permeable channel. The expression of TRP channels in CHO cells demonstrates that both WIN and AM1241 activate TRPA1 and, by doing so, attenuate capsaicin and mustard oil responses. Using TRPA1-specific small interfering RNA or TRPA1-deficient mice, we show that the TRPA1 channel is a sole target through which WIN and mustard oil activate sensory neurons. In contrast, AM1241 activation of sensory neurons is mediated by TRPA1 and an unknown channel. The knockdown of TRPA1 activity in neurons completely eliminates the desensitizing effects of WIN and AM1241 on capsaicin-activated currents. Furthermore, the WIN- or AM1241-induced inhibition of capsaicin-evoked nocifensive behavior via peripheral actions is reversed in TRPA1 null-mutant mice. Together, this study demonstrates that certain cannabinoids exert their peripheral antinocifensive actions via activation of the TRPA1 channel on sensory neurons.