Capsaicin - A cause of and a cure for pain

• the main compound in chili peppers (genus Capsicum) that makes them so gosh darn spicy
• the hottest chili in the world is the Naga Jolokia (I know you were wondering)
• is one of six natural capsaicinoids found in chili peppers, all of which produce a wonderful burning sensation when they come in contact with mucous membranes
• the burning sensation it produces is due to it activating vanilloid receptor subtype 1 (TRPV1), a type of ionotropic receptor found on neurons called C-fibres that carry pain signals (particularly those associated with excessive heat or abrasive damage, in other words, things that produce a burning sensation) to the brain
• does not actually cause tissue damage, instead produces the sensation of it by hijacking the neural pathway by which the sensation is transmitted to the brain
• has been used to treat peripheral pain (pain not originating in the brain or spinal cord) associated with conditions including rheumatoid arthritis, diabetic neuropathy, and postherpetic neuralgia (pain occurring after a bout with shingles)
• topical preparations (ointments, creams) have been used for minor inflammatory joint and muscle pain
• can also be used to treat perennial nonallergic rhinitis (PNAR), which is essentially hay fever only the afflicted individual has no known sensitivities to specific allergens (e.g. pollen)
• in all of these applications, the administration of capsaicin initially worsens the condition being treated due to the stimulation of C-fibres, but with repeated administration is thought that the C-fibres get overstimulated such that they become depleted of the neurotransmitters and neuropeptides (e.g. substance P) that mediate their actions, leading to the loss of pain sensation and neurogenic (neuron-sourced) inflammation/reduced nasal hyperreactivity (congestion and runny nose)
  
• a typical treatment regime involves first the application of a topical anaesthetic followed by capsaicin in order to avoid the burning sensation it produces
• is neat because it represents an analgesic that is neither an NSAID nor an opioid and one that acts directly and selectively on pain transmitting neurons
• currently under investigation as a possible treatment for diabetes and cancer
• has been claimed to have antigenotoxic and anticarcinogenic effects by some researchers, yet has been reported to be a tumour promoter and carcinogen by others (the jury is still very much out on this one)
• is bioactivated by CYP2E1 (a drug-metabolizing enzyme) to reactive species that are capable of binding to the enzyme and potentially to DNA, which would be expected to cause mutations that could lead to the development of cancer
  

- Greiner AN, Meltzer EO. Pharmacologic rationale for treating allergic and nonallergic rhinitis. J Allergy Clin Immunol. 2006 Nov;118(5):985-98.
- Szolcsanyi J. Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides. 2004 Dec;38(6):377-84.
- Zhou S et al. Herbal bioactivation: the good, the bad and the ugly. Life Sci. 2004 Jan 9;74(8):935-68.
- http://en.wikipedia.org/wiki/Capsaicin