Capsaicin is the pungent ingredient found
in chili peppers from the genus Capsicum (Solanaceae) and,
when eaten, gives the peppers their "hot" taste.1,2 As it
relates to its use in medicine, capsaicin is most commonly used for the
treatment of pain and can be purchased in the form of a topical cream or gels
in concentrations ranging from 0.025% to 0.075%. Common brand names
include Arthicare, Capsagel, Capzasin-P, Zostrix and Zostrix-HP and can be
without a prescription in most countries. The most common pain syndromes
treated with topical capsaicin include rheumatoid arthritis, osteoarthritis and
psoriasis.2-4 Topical capsaicin can be a useful adjunct in pain
management, especially when escalating doses or addition of other medications
is likely to lead to intolerable systemic side effects or drug interactions.1-4
Unfortunately, this treatment is plagued with a slow onset of therapeutic
benefit, during which time patients frequently experience feelings of pain or
burning, redness, and possibly minor swelling in the area of
Why and how does capsaicin cause this side effect prior to
producing noticeable pain relief for the patient?
the skin, there any many free nerve endings that are connected to and activate
sensory afferent nerve fibers when stimulated. Sensory afferent nerve fibers
carry nerve impulses generated in the peripheral tissue toward the spinal cord,
which then communicate with other neurons in the spinal cord to eventually
deliver the message of pain for perception and interpretation by the brain.5
The nerve impulse or fiber is sensory if it carries pain, temperature, touch,
vibration, pressure or proprioceptive information to the brain.5 Also, it
is important to know that there are different types of pain conducting sensory
nerve fibers such as A-alpha, A-beta, A-delta, and C, which are listed from
fastest conduction velocity to the slowest.5 Therefore, C-nerve fibers
are the slowest and can be further differentiated from other nerve fibers as
they are also unmyelinated.5
Why is this level of
differentiation of sensory nerve fibers so important when considering
capsaicin's initial mechanism of action?
Acute pain is transmitted primarily by A-delta
sensory nerve fibers to the spinal cord and chronic or slow pain is transmitted
primarily by unmyelinated C sensory afferent nerve fibers (C nerve fibers).5
The lack of myelination is, in part, why the pain is transmitted slower with C
nerve fibers than A-delta fibers. Interestingly, capsaicin is a noxious
substance that basically stimulates the free nerve endings of the C nerve
fibers (see figure 1).6 Upon binding and activation, capsaicin causes the
C nerve fiber to enter an excitatory state that will ultimately result in the
brain interpreting the depolarization as a painful or burning feeling.
This is most prevalent during the initial stages capsaicin use.
- Holzer P. Capsaicin: cellular targets, mechanisms of action, and
selectivity for thin sensory neurons. Pharmacol Rev 1991;43:143-201.
L, Moore RA, Derry S et al. Systematic review of topical capsaicin for
the treatment of chronic pain. BMJ 2004;328:991.
CL, Schnitzer TJ, Lipstein E et al. Treatment of arthritis with topical
capsaicin: a double-blind trial. Clin Ther 1991;13:383-95.
GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful
osteoarthritis of the hands. J Rheumatol 1992;19:604-7.
- Snell RS. Chapter 4. The Spinal Cord and the Ascending Pathway and Descending Tracts. In: Clinical Neuroanatomy. 6th Ed. Snell RS eds. Lippincott Williams and Wilkins. Philadelphia, PA. 2006.
SJ, Stansfeld CE, Brown DA et al. The mechanism of action of capsaicin
on sensory C-type neurons and their axons in vitro. Neuroscience
P. Local effector functions of capsaicin-sensitive sensory nerve
endings: involvement of tachykinins, calcitonin gene-related peptide and
other neuropeptides. Neuroscience 1988;24:739-68.
- Maggi CA, Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 1988;19:1-43.
CJ, DiMicco JA, Jacobowitz DM et al. Effect of capsaicin
administration of neonatal rats on the substance P content of discrete
CNS regions. Brain Res 1981;222:428-31.
- Gamse R, Molnar A, Lembeck F. Substance P release from the spinal cord slices by capsaicin. Life Sci 1979;25:629-36.
A, Gamse R, Petermann J et al. Simultaneous release of several
tachykinins and calcitonin gene-related peptide from rat spinal cord
slices. Neurosci Lett 1986;63:310-4.