1. Marylene. Kyriazis, Pharm.D.
Modulation of TRPV1 (Capsaicin) Receptor Activity by Mannitol 30% Topical Cream
Helene Bertrand, M.D.,
Marylene. Kyriazis, Pharm.D.
K. Dean Reeves, M.D.

2. Conflict of interest Presenter disclosure
Faculty: Dr. Helene Bertrand Relationship with commercial interests: Dr. Bertrand has developed and holds a patent pending and holds shares in a company making the 30% mannitol cream used in the randomized placebo-controlled study which is the subject of this presentation.

3. Program disclosure of commercial support
The 30% mannitol cream is not being manufactured.
It is not for sale at present.
No commercial support.

4. Mitigation of bias 30% mannitol cream is not for sale.
The study, which will be discussed, was randomized, double-blind, and placebo-controlled, making bias almost impossible.
The purpose of this presentation is to show the effectiveness of mannitol in down-regulating the TRPV1 receptor, not in recommending the use of this cream.

5. Cream questionnaire
Please keep a record of your use of the pain cream! Note the area treated, note the date, the time, how bad your pain is from 0=no pain to 10= the worst pain ever, before and 30 minutes after applying the cream. Note how soon it works in minutes, and how long it lasts in hours.
Area
Date
Time
Pain
Before
0-10
30 min.
After
Mins to relief
Hrs.
relief
lasts
Com
ment

6. 30% Mannitol Cream Statistics N=123
Average time to pain relief: minutes
Average duration of pain relief: 10 hours
Average degree of pain relief: %
Average relief from narcotics : 30%
Areas most relieved: Skin 76% subjects
Leg 75%
Knee 74%
Foot 70%
Thigh 69%
Hand 68%
Shoulder 61.5% 20

8. Cream Ingredients
Capsaicin Cream: Natural Health Products Directorate (NHPD) number Active ingredient capsicum annum .075 percent in a base of Ariacel 165 (Glycerol mono and distearate and polyoxyethylene-stearate) Benzyl Alcohol, Cetyl Alcohol, Glyceryl Monostearate, Isopropyl myristate, purified water, Sorbitol and White Petrolatum.
Mannitol Cream: 30% mannitol in a base of isopropyl palmitate, caprylic capric triglyceride, propylene glycol, ceteareth 20, cetearyl alcohol, glyceryl stearate, polyethylene glycol 100 stearate, dimethicone, octyldodecanol, lecithin, ethylhexyl glycerin and phenoxy ethanol.
Vehicle Cream: Same base as the mannitol cream but without any mannitol.

10. All qualifying participants (#25)
Side of Lip Randomized 25
.1 ml .075% Capsaicin Applied to Upper Lip Until 5 Minutes or Until 8/10 on NRS Heat Scale, then Capsaicin removed.
Mannitol Lip 25 25
Vehicle Lip
0.2 ml 30% Mannitol Cream in Vehicle Cream to Upper Lip.
0.2 ml Vehicle Cream to Upper Lip 25 25
NRS 0-10 Heat Scale Time 0 through 10 Minutes at 1 Minute
Intervals

12. Significance at Each Minute
.012
.002
.001
.106
.403
.207
.109
Significance at Each Minute

13. Significance at Each Minute
Significance at Each Minute

14. TRPV1 antagonist relieves itch As well as pain
JW Yun et al. antipruritic effect of TRPV1 antagonist in murine atopic dermatitis and itching models Journal of investigative dermatology [2011] 130, 1576 – 1579
Chun-Shui Yu Study on HIF-1α Gene Translation in Psoriatic Epidermis with the Topical Treatment of Capsaicin Ointment ISRN Pharm. 2011; 2011: online Jun 22, 2011. doi:   /2011/821874 *
Won-Sik Shim, Min-Ho Tak, Mi-Hyun Lee, Minjung Kim, et al. TRPV1 Mediates Histamine-Induced Itching via the activation of Phospholipase A2 and 12-Lipoxygenase The Journal of Neuroscience, February 28, 2007 • 27(9):2331–2337