Capsaicin desensitization effects

Preexposure to menthol and capsaicin can desensitize the response to other stimuli, i.e. the thermal response to a warm solution or the irritation upon a second application of capsaicin (26,27). After capsaicin desensitization, the nerves no longer respond to burning or stinging but still give sensations of numbness or warmth. This effect is most noticeable upon further stimulation with capsaicin and less for the irritants, cinnamic aldehyde and NaCl. This sensitization and the fact that these sensations build in intensity on repeat application differentiate them from the "basic tastes", which adapt to the sensation on repeated application. 

A further point concerns the differences between the effects of adult and neonatal capsaicin administration. In some respects adult animals which have been treated neonatally with capsaicin show similar functional impairments as adult animals which have been desensitized to the compound. However, as will be elaborated upon below, there is an important distinction between assault of neonatal and adult animals with high doses of capsaicin. For reasons which will become clear, in the adult animals capsaicin has been referred to in the literature as a sensory neuron blocking agent producing at high doses capsaicin desensitization, whereas in neonatal animals it is a sensory neurotoxin producing sensory neuron lesions. ... 

Further tissue-specific effects were observed in membrane preparations obtained from capsaicin-desensitized rats. The basal adenylate cyclase activity was dramatically increased in the preoptic hypothalamus of these animals but unchanged in the cerebellum or cortex. Moreover, in the cerebellum, normal stimulatory responses were obtained, whereas in the preoptic region not only did capsaicin desensitization cause a failure in the ability of capsaicin to stimulate adenylate cyclase in vitro, but it also produced an inhibition of the augmented basal enzyme activity (Jancso and Wollemann, 1977). Prior exposure of cortical membranes to capsaicin in vitro was also found to increase basal adenylate cyclase activity, and this effect was found to be dependent on calcium ions (Horvath et ai, 1979). 

T Karrer, L Bartoshuk. Effects of capsaicin desensitization on taste in humans. 

At present, two conceptually different (but not mutually exclusive) therapeutic strategies are being pursued in the vanilloid field one is to use optimized TRPVl agonists to desensitize (in practice, defunctionalize) capsaicin-sensitive nerves [1, 21] and the other is to employ small molecule antagonists for the pharmacological blockade of TRPVl [7, 8]. The first approach is time-proven, but is riddled by known side-effects such as pain [1], as well as emerging concerns such as impaired control of cancerous growth [22]. 

The most important adverse effect of capsaicin is the initial burning sensation that it produces. Intravesical capsaicin induces intense suprapubic pain during intravesical instillation that may be made tolerable by lidocaine in some but not all patients. Capsaicin also frequently causes a transient worsening of the urinary conditions before improvement of symptoms due to desensitization of bladder afferents becoming evident. In patients with high spinal cord lesions capsaicin might provoke life-threatening autonomic dysreflexia. 

Clinical use Resiniferatoxin has been characterized as an ultrapotent sensory neuron desensitizing agent. It is 100 to 10,000 times more potent than capsaicin, has a longer duration of action, is much less irritating, and is substantially more effective in producing neural... 

Capsaicin is supplied pharmaceutically as a cream, gel. or lotion. The First application of the piepatation produces intense pain and irritation at the site of application, but usually no skin reaction occurs. Repeated applications cause desensitization, and eventually analgesic and anti-inflammatory effects occur., Stimulation of afferent nerve tracts causes a heat. sensation. 

With prolonged or repeated exposure to capsaicin (3), however, one will eventually beeome insensitive to its effects as excessive cation influx leads to death of the neurons. It is for this reason that people can cultivate a toleranee for spicy food over time, enabling some to have the ability to eat peppers so hot that their mere smell would make the eyes of those less accustomed water profusely. The perhaps more significant feature is this desensitization suggests that capsaicin could serve as an analgesic to mitigate the pain and inflammation associated with several disorders such as... 

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