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Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors.

Abstract：

:Peripheral mediators can contribute to the development and maintenance of inflammatory and neuropathic pain and its concomitants (hyperalgesia and allodynia) via two mechanisms. Activation or excitation by these substances of nociceptive nerve endings or fibers implicates generation of action potentials which then travel to the central nervous system and may induce pain sensation. Sensitization of nociceptors refers to their increased responsiveness to either thermal, mechanical, or chemical stimuli that may be translated to corresponding hyperalgesias. This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons. Manifestations, receptor molecules, and intracellular signaling mechanisms of the effects of these mediators are discussed in detail. With regard to signaling, most data reported have been obtained from transfected nonneuronal cells and somata of cultured sensory neurons as these structures are more accessible to direct study of sensory and signal transduction. The peripheral processes of sensory neurons, where painful stimuli actually affect the nociceptors in vivo, show marked differences with respect to biophysics, ultrastructure, and equipment with receptors and ion channels compared with cellular models. Therefore, an effort was made to highlight signaling mechanisms for which supporting data from molecular, cellular, and behavioral models are consistent with findings that reflect properties of peripheral nociceptive nerve endings. Identified molecular elements of these signaling pathways may serve as validated targets for development of novel types of analgesic drugs.

journal_name

Physiol Rev

journal_title

Physiological reviews

authors

Petho G,Reeh PW

doi

10.1152/physrev.00048.2010

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

1699-775

issue

eissn

0031-9333

issn

1522-1210

pii

92/4/1699

journal_volume

pub_type

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Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors.