In vitro prostanoid release from spinal cord following peripheral inflammation: effects of substance P, NMDA and capsaicin

Abstract

1 Spinal prostanoids are implicated in the development of thermal hyperalgesia after peripheral injury, but the speci®c prostanoid species that are involved are presently unknown. The current study used an in vitro spinal superfusion model to investigate the eect of substance P (SP), Nmethyl-d-aspartate (NMDA), and capsaicin on multiple prostanoid release from dorsal spinal cord of naive rats as well as rats that underwent peripheral injury and in¯ammation (knee joint kaolin/ carrageenan). 2 In naive rat spinal cords, PGE 2 and 6-keto-PGF 1a , but not TxB 2 , levels were increased after inclusion of SP, NMDA, or capsaicin in the perfusion medium. 3 Basal PGE 2 levels from spinal cords of animals that underwent 5 ± 72 h of peripheral in¯ammation were elevated relative to age-matched naive cohorts. The time course of this increase in basal PGE 2 levels coincided with peripheral in¯ammation, as assessed by knee joint circumference. Basal 6-keto-PGF 1a levels were not elevated after injury. 4 From this in¯ammation-evoked increase in basal PGE 2 levels, SP and capsaicin signi®cantly increased spinal PGE 2 release in a dose-dependent fashion. Capsaicin-evoked increases were blocked dose-dependently by inclusion of S(+) ibuprofen in the capsaicin-containing perfusate. 5 These data suggest a role for spinal PGE 2 and NK-1 receptor activation in the development of hyperalgesia after injury and demonstrate that this relationship is upregulated in response to peripheral tissue injury and in¯ammation.

Nonopioid Actions of Intrathecal Dynorphin Evoke Spinal Excitatory Amino Acid and Prostaglandin E2Release Mediated by Cyclooxygenase-1 and -2

“…This increase by NMDA and dynorphin was reduced by an NMDA antagonist, emphasizing the importance of NMDA receptor activation. These results are consistent with our work showing that intrathecal NMDA stimulates PGE 2 release (Malmberg and Yaksh, 1995;Dirig and Yaksh, 1999) and suggest that dynorphin-evoked PGE 2 release occurred by direct activation of the NMDA receptor or through an initial release of excitatory amino acids as considered above. The apparent difference in sensitivity of the PGE 2 release evoked between NMDA and dynorphin to the COX-1 inhibitor SC 58560 (see below) now suggests an additional action of dynorphin, independent of NMDA receptor activation.…”

“…Such observations link spinal dynorphin to nociception, because intrathecal NMDA also produces hyperalgesia (Malmberg and Yaksh, 1992) and NMDA block diminishes hyperalgesia. Importantly, hyperalgesia produced by intrathecal NMDA is blocked by cyclooxygenase (COX) inhibitors (Malmberg and Yaksh, 1992), a finding consistent with the ability of intrathecal NMDA to evoke spinal prostaglandin E 2 (PGE 2 ) release (Malmberg and Yaksh, 1992;Sorkin, 1993;Dirig and Yaksh, 1999) through a constitutive spinal COX. The two COX isozymes (COX-1 and COX-2) are constitutively expressed in spinal cord (Svensson and Yaksh, 2002).…”

Anandamide Activates Vanilloid Receptor 1 (VR1) at Acidic pH in Dorsal Root Ganglia Neurons and Cells Ectopically Expressing VR1

“…Platelets, leukocytes, spinal cord astrocytes, and other cell types respond to tissue injury with eicosanoid release (1)(2)(3). A linkage between generation of eicosanoids and pain sensation has been proposed; however, the range of mechanisms has not been fully determined (4).…”

Innovations in Pain Management: Morphine Combined with Omega-3 Fatty Acids

“…The synthesis and release of prostaglandins from astrocytes [26,27] and neurons [28] in the spinal cord can be induced by the activation of NMDA receptors [29,30] and NK-1 receptors. Moreover, these prostaglandins act retrogradely (positive feedback) on primary afferent terminals to stimulate further the release of excitatory amino acids (l-glutamate) and neuropeptides (SP) [31 -33].…”