MSM Gel, ( Joint, Tissue & Muscle Support Gel), works when applied topically to the skin. The discomfort you feel is from the Leukotrienes. This is one of a group of chemicals produced by the body that accompanies inflammation. All inflammation is PAIN. When the MSM Joint, Tissue & Muscle Support Gel is applied topically, the leukotrienes are blocked. Feel the difference in 5 to 10 minutes. This lasts for 8 to 18 hours.