Sensory neuron mechanisms, capsaicin

CAPSAICIN A CHEMICAL PROBE FOR SENSORY NEURON MECHANISMS... 

Pharmacology Capsaicin is a natural chemical derived from plants. Although the precise mechanism of action is not fully understood, evidence suggests that the drug renders skin and joints insensitive to pain by depleting and preventing reaccumulation of substance P in peripheral sensory neurons. 

Holzer, P. Capsaicin cellular targets, mechanisms of action, and selectivity for thin sensory neurons, Pharmacol. Rev. 1991, 43, 143-201. 

Dray, A. (1992) Mechanism of action of capsaicin like molecules on sensory neurons. Life Science 51(23), 1759-1765. 

Capsaicin, like the other irritant RCAs, also causes bronchoconstriction, but the mechanism is uncertain. Capsaicin releases substance P that can cause bronchoconstriction directly by activation of specific receptors or by release of histamine or other mediators. It may also cause reflex bronchoconstriction by stimulating C fibers in both pulmonary and bronchial circulation. Therefore, bronchoconstriction may be secondary to substance P release, or to a vagal reflex. The altered neurophysiology of sensory neurons in the airway mucosa induces the release of tachykinins and neurokinin A, which causes neuro-mediated inflammation of the epithelium, airway, blood vessels, glands, and smooth muscles. This leads to bronchoconstriction, mucus secretion, enhanced vascular permeability, and neutrophil chemotaxis. 

In this maimer, capsaicin binds to the same group of nociceptors which lead to the sensation of pain, heat, and acid. Then lead for a reduction in pain and inflammation by depleting the neurotransmitter pain signaling [111]. This effect has been observed for example when an intraarticular injection of capsaicin is administrated to reduce the mechanical hyperalgesia induced in osteoarthritis [112]. Additionally, capsaicin appears to be effective in protecting bone from osteoarthritic damage, supporting the hypothesis that capsaicin-sensitive sensory neurons contribute to bone lesions. Therefore capsaicin may be useful for the development of new therapeutic approaches to pain control and prevention of osteoarthritis-dependent bone loss [113]. 

Marsh SJ, Stansfeld CE, Brown DA et al. (1987). The mechanism of action of capsaicin on sensory c-type neurones and their actions in vitro. Neuroscience, 23, 275-289. 

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