Transduction Mechanisms

The availability of molecules eliciting pain has provided important evidence concerning the transduction of noxious stimuli. An extract from hot peppers known as capsaicin is a powerful stimulant of nociceptors and, when administered to human subjects, it evokes the sensation of noxious heat. The receptor for this molecule, VR1, a member of the TRP receptor family, has been cloned and has been found to be expressed in small sensory neurons coexpressing other markers characteristic of nociceptors. When VR1 is expressed in oocytes, they exhibit sensitivity to noxious heat and other stimuli that activate nociceptors, such as protons (low pH). The response of VR1 to heat can be enhanced when the pH of the surrounding medium is reduced, corresponding to the reduced threshold to heat observed behaviorally during inflammatory conditions when pH naturally falls. Thus, this receptor is a logical candidate to be an important participant in the transduction of these nociceptive stimuli. No corresponding molecule for high-threshold mechanorecep-tors has been definitively identified.

ATP and its associated receptor family (the P2X family) have also been implicated in peripheral noci-ceptive events. Damaged cells release ATP, and the fraction of the cytosol that elicits pain when applied to blisters is rich in ATP. In rats, a member of the P2X receptor family, P2X3, is expressed exclusively in sensory neurons, and evidence suggests that its expression is confined to nociceptors. Together these findings suggest that ATP could be an important agent for evoking pain when tissue is damaged.

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