Prostaglandin E2 and I2 facilitate noxious heat-induced spike discharge but not iCGRP release from rat cutaneous nociceptors

TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins

“…It should be noted that the ex vivo preparations we used (that is, the superfused trachea and the isolated tongue), in contrast to the skin in vivo , cannot reflect secondary inflammatory reactions, like plasma extravasation, accumulation of inflammatory mediators (for example, bradykinin, thrombocytes and immune cells), which, together, may complement or amplify, like we found with HNE or acrolein, the excitatory effects of LPS on TRPA1 to activate nociceptors58. The modest but significant effect of LPS alone on tracheal CGRP release is not surprising, because even prostaglandin E2, the most widely acknowledged nociceptor sensitizer, shows no effect of its own on nociceptor discharge and CGRP release but ‘only’ facilitates heat and chemical responses59. Finally, these avascular ex vivo preparations cannot be compared directly with dissociated sensory neurons in culture with respect to chemosensitivity, because the nerve endings do not reach the very surface of the mucosa, formed by epithelial cells and their tight junctions.…”

Involvement of α2‐adrenoceptors in inhibitory and facilitatory pain modulation processes

“…Similar to previous studies (Lang et al., ; Klein et al., ; Pfau et al., ; Vo and Drummond, , ), hypersensitivity to sharpness and pressure‐pain developed at the HFS‐treated site (primary hyperalgesia), and hypersensitivity to sharpness also developed nearby (secondary hyperalgesia). In addition, heat hyperalgesia developed at the primary site, possibly because the electric current triggered release of prostaglandins (Ferrell et al., ; Tartas et al., ; Derow et al., ). Sensitivity to heat remained stable after HFS in the secondary area but decreased at the control site.…”

Neural Mechanisms of Inflammation-Induced Fever

“…In addition to the vagus nerve, somatic afferent fibers have also been suggested to be involved in the febrile response. Similar to the nodose ganglion, dorsal root ganglia have been reported to express IL-1R1 and EP 3 receptors ( Binshtok and others 2008 ; Nakamura and others 2000 ), and peripheral nerves have been shown to respond to IL-1β and PGE 2 , although these inflammatory mediators were found to sensitize the nerves to other stimuli rather than to elicit a discharge per se ( Binshtok and others 2008 ; Derow and others 2007 ). In line with the idea that fine afferent fibers throughout the body sense the internal milieu and through their afferent discharge influence various autonomic relay structures to maintain homeostasis ( Craig 2002 ), it is conceivable that somatic afferent fibers could mediate the febrile response to localized peripheral inflammation.…”