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In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2343 participants) was (95% confidence interval ( CI ) to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was ( to ) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID , but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis.
The second direction is that given enough stimulus to the TRPV1 receptors and the concomitant release of Substance P, it is possible to deplete the cells of Substance P to the point that cells can no longer transmit the pain signal across the cell--or from one cell to the next. But since TRPV1 responds to more stimuli than just pain--the bio-chemicals in herbs and spices, for example--it is possible to use that quality to overstimulate the receptors to the point that all Substance P is depleted and the cells can no longer transmit pain.