Topical Mannitol blocks pain

New research conducted by Dr Helene Bertrand et al out of North Vancouver confirms that topical mannitol cream reduces the pain felt by application of capsaicin. Sensory nerves involved in neuropathic pain contain receptors (TRPV1) which are  sensitive to capsaicin. It is already known from research by Denis Burdakov et al that dextrose indirectly affects some nerve receptors via a potassium ion channel, though this effect is best at a neutral pH (which is why we now buffer the D5W we use in perineural and trigger point injections). It is interesting to note that mannitol also appears to do so, though the mechanism has not been confirmed. This supports earlier clinical observations that subcutaneous injections of 5% dextrose or 5% mannitol around constricted or inflamed sensory nerves relieves neurogenic pain. Dr Bertrand has also noted that topical mannitol cream is helpful in relieving neuropathic pain in many individuals. 

Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.5/12/2015

PM&RPubMedID: 25978942Bertrand H, Kyriazis M, Reeves KD, Lyftogt J, Rabago D. Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial. PM R. 2015;.
BACKGROUND
Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV-1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain.

OBJECTIVE
To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model.

DESIGN
Randomized, placebo-controlled, double-blind clinical trial.

SETTING
Outpatient pain clinic.

PARTICIPANTS
Twenty-five adults with pain-free lips.

METHODS
Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner.

OUTCOME MEASURES
Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups.

RESULTS
Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001).

CONCLUSIONS
Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect.