The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat

Abstract

The role of PGE2 in the sensitization of high-threshold tarsal joint mechanoreceptors (putative nociceptors) has been investigated in 11 arthritic and 16 normal rats. Injections of a low dose of Freund's complete adjuvant at multiple sites into the tissues surrounding the ankle joint induced a chronic unilateral monoarthritis in the injected limb. Measurements of both spontaneous activity and responses of tarsal joint mechanoreceptors to repeated graded mechanical stimuli were made. All of the mechanoreceptors examined had afferent fibres with conduction velocities in the C- or A-delta range. Using this new model of joint inflammation we have shown that lysine acetylsalicylate reduces the mechanical sensitivity of these joint mechanoreceptors and reduces the spontaneous activity in afferent nerve fibres. Prostaglandin E2 is unable to restore either the spontaneous activity in the afferent axon or the mechanical sensitivity of tarsal joint mechanoreceptors after lysine acetylsalicylate in the arthritic rat. Similarly, PGE2 does not sensitize or excite tarsal joint mechanoreceptors in the normal rat. In the normal rat, however, PGE2 potentiates the excitatory action of bradykinin and enhances the sensitizing effect of bradykinin on the responses of joint mechanoreceptors to mechanical stimulation when both substances are injected simultaneously. These results indicate that PGE2 is not important in the sensitization of these joint mechanoreceptors in this model of chronic joint inflammation but that in other circumstances PGE2 may be able to contribute to a sensitization of joint mechanoreceptors by enhancing the action of bradykinin.

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).…”

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…IID1B). Exogenously applied prostanoids (mostly PGE 2 , PGE 1 , and PGI 2 ), however, typically failed to cause neuronal spike discharges (70,96,247,287,326,403,499,501,502,616) or pain (121, 294,366,512,618).…”

5HT4Receptors Couple Positively to Tetrodotoxin-Insensitive Sodium Channels in a Subpopulation of Capsaicin-Sensitive Rat Sensory Neurons

“…Proinflammatory agents such as serotonin (5HT), prostaglandins, and adenosine are derived from a number of sources (Cooper and Sessle, 1992). Interactions between such agents and endings of thinly myelinated and unmyelinated nociceptive afferents induce activity, decrease threshold, and increase suprathreshold mechanothermal reactivity (Handwerker, 1976;Kumazawa and Mizumura, 1980;Mense, 1981;Martin et al, 1987;Schaible and Schmidt, 1988;Lang et al, 1990;Grubb et al, 1991;Herbert and Schmidt, 1992).Contributions to hyperesthesia by proinflammatory agents are possibly achieved by modulation of membrane currents involved in the initiation and repolarization of action potentials in nociceptive endings, as well as induction of edema in the surrounding matrix (Cooper, 1993). The study of acutely isolated dorsal root ganglion (DRG) cell bodies may be usef ul in determining the roles of various ion channels in the actions of proinflammatory agents on nociceptor f unction.…”