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How To Use It. Penetrex is a topical cream, so you just take some of the cream and apply it to the areas in pain. Rub it in until you are sure it has been absorbed through the skin (you should see no more of the cream).You should do this 4 times each day for the first week to week and a half.enetrex is an anti-inflammatory agent specifically designed to reduce inflammation in your body. It is a topical creamâyou simply apply it to the area of pain, let it be absorbed, and feel the pain go away.