Dermatological Agents
Topical Analgesics

Description: Capsaicin is an external analgesic. It is also the major pungent ingredient of hot chile pepper. Capsicum preparations (e.g., capsaicin, capsicum, and capsicum oleoresin) are derived from the fruit of various species of plants of the Solanaceae (i.e., nightshade) family. Capsicum contains about 1.5% of an oleoresin, the major component of which is capsaicin. Preparations of capsaicin are available without a prescription and are marketed for the temporary relief of pain from arthritis, or for the relief of minor aches and pains of muscles and joints. Capsaicin is also indicated for the treatment of neuralgias due to shingles or diabetes, as well as other types of neurogenic pain (e.g., postmastectomy pain). In the treatment of osteoarthritis, topical capsaicin is considered a second-line agent either alone or as an adjunct to acetaminophen or aspirin therapy. A high dose capsaicin dermal patch (NGX-4010) is in phase III clinical development by NeurogesX, Inc. for the treatment of neuropathic pain associated with human immunodeficiency virus (HIV) or herpes simplex infection.

Mechanism of Action: Capsaicin depletes and prevents reaccumulation of substance P in peripheral sensory neurons. Substance P is found in slow-conducting, unmyelinated type C neurons that innervate the dermis and epidermis. Substance P is thought to be the primary chemical mediator of pain impulses from the periphery to the central nervous system. It can also be released into joint tissues, where it activates inflammatory substances involved in the development of rheumatoid arthritis. By depleting substance P, capsaicin renders skin and joints insensitive to pain since local pain impulses cannot be transmitted to the brain. When capsaicin therapy is discontinued, substance P reaccumulates and neuronal sensitivity returns to normal. Capsaicin is not a traditional counterirritant since it does not produce vasodilation.

Pharmacokinetics: Capsaicin is applied topically to the skin. Once applied, the duration of action of capsaicin is 4—6 hours. Pain relief is usually noted within 2 weeks after therapy has begun, although the maximum effect may not be observed for 4—6 weeks.

Drug Information Provided by
Gold Standard Inc. � 2007