Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2.

Abstract

SUMMARY1. In cats anaesthetized with ac-chloralose extracellular recordings were made from fine afferent units belonging to the medial articular nerve of the knee joint. The excitatory and sensitizing effects on articular afferents of prostaglandin E2 (PGE2) applied intra-arterially close to the joint were examined.2. Bolus injections of PGE2 doses of 0-03-30 ,tg excited about 60% of both the group III (conduction velocity 2-5-20 m/s) and the group IV units (conduction velocity < 2-5 m/s). The duration and size of the responses were dose dependent consisting in most cases of low-frequency discharges which lasted up to several minutes. Excitation was found among afferents with low and high mechanosensitivity.3. Among the group III units PGE2 sensitized 64% for their responses to movements and 50 % for their responses to bradykinin (applied intra-arterially close to the joint). Sensitization did not depend on the mechanical threshold previous to chemical stimulation. Among the group IV units PGE2 sensitized only 25 % for their responses to movements but 75 % for their reactions to bradykinin. In group IV fibres a low mechanical threshold predisposed for sensitization to movements and a higher threshold for sensitization to bradykinin.4. Some units were sensitized and excited, others were either sensitized or excited and some units were not affected by PGE2. We conclude that PGE2 induces in a large proportion of fine articular afferents of normal joints discharges which are similar to those induced by an experimental inflammation. Thus PGE2 may be an inflammatory mediator which has a major role in the generation of the afferent activity developing in the course of an arthritis.

A Transient Receptor Potential Vanilloid 4-Dependent Mechanism of Hyperalgesia Is Engaged by Concerted Action of Inflammatory Mediators

“…Conceivably, primary afferent nerve fibers that express TRPV4 as their only mechanical transducer would exhibit properties of silent nociceptors, becoming mechanically responsive only in pathological conditions. Indeed, in parallel to our observations, inflammation induced by carrageenan or by inflammatory soup activates silent nociceptors Schmidt, 1985, 1988a;Xu et al, 2000), but PGE 2 alone is insufficient (Mizumura et al, 1987;Schaible and Schmidt, 1988b;Lang et al, 1990;Grubb et al, 1991;Handwerker et al, 1991;Kress et al, 1992).…”

Diminished Inflammation and Nociceptive Pain with Preservation of Neuropathic Pain in Mice with a Targeted Mutation of the Type I Regulatory Subunit of cAMP-Dependent Protein Kinase

“…Rather, PGE 2 -evoked hyperalgesia in this model results from a sensitization of the C-fiber terminal, which does not require C a 2ϩ -dependent neurotransmitter release. Sensitization is manifest as a lowered threshold for firing of the terminal; this results in a behavioral allodynia in which non-noxious stimuli can evoke withdrawal reflexes and pain behavior (Martin et al, 1986;Schaible and Schmidt, 1988).…”

Neuropeptides and Neurogenic Mechanisms in Oral and Periodontal Inflammation

“…Bradykinin has been shown to bind to B 2 receptors on sensory neurons, resulting in the activation of phospholipase C and ultimately the release of calcium from intracellular stores, thereby triggering neuropeptide exocytosis (Burgess et al, 1989). The pro-inflammatory prostaglandins E 2 and I 2 (PGE 2 and PGI 2 ) have been shown to bind to specific receptors on sensory nerves, where they lower the firing threshold (Schaible and Schmidt, 1988). Recent work has demonstrated that bradykinin and PGE2 have a positive interaction in evoking CGRP release from bovine dental pulp (Goodis et al, 2000).…”