The neuropeptide substance P is involved in the inflammation and pain in arthritis; capsaicin serves to deplete this substance. In a study on patients with osteoarthritis and rheumatoid arthritis, researchers came to the conclusion that capsaicin cream 0.025% is an efficient and safe treatment for arthritis.
It so seems that capsaicin specifically stimulates non-myelinated C fibers and results in release of substance P. Prolonged administration of capsaicin inversely depletes reservoirs of substance P and probably other neurotransmitters from sensory nerve terminals. This results in reduction or elimination of transmission of pain stimulations from peripheral nerves to the higher centers. In most clinical trials, in patients suffering post herpetic neuralgia, diabetic neuropathy or osteoarthritis, adjuvant treatment with topical capsaicin has resulted in more efficient management of pain and no severe systemic adverse reaction has been reported.
Capsaicin specifically affects primary afferent sensory nerves, so as to cause –probably through a direct reaction with the ion-receptor complex in the membrane– opening of specific ion channels. Those nerves sensitive to capsaicin are involved in perception of pain and are responsible for the neurologic share of the inflammatory response and may as well have efferent function in target peripheral tissues. Apart from stimulative effects, capsaicin is capable of having analgesic and anti-inflammatory effects.