Mechanisms of Hyperalgesia: Regulation of Nociceptor Activation and Excitability

摘要

Hyperalgesia is a hallmark of inflammatory pain. Alterations in the properties of primary afferent neurons may partly explain the condition. Among the changes that have been described are alterations in the properties of voltage-gated sodium and potassium channels to make sensory neurons more electrically excitable. In addition, a variety of primary signal transducing molecules, such as the proton-gated heat sensor TRPV1, are regulated by inflammatory mediators to alter the gain of the sensory system. Phospho-rylation of receptors and channels seems to be a common mechanism of tuning the sensitivity of sensory neurons to noxious input. In this chapter, we discuss genetic methods to determine the role of receptors and channels in setting pain thresholds, and compare the effectiveness of three such approaches: the use of antisense oligonucleotides, the downregulation of mRNA using small interfering RNA, and. the generation of null mutant mice.