Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord

Kainate receptor pharmacology and physiology

“…Capsaicininduced hyperalgesia an allodynia is humans is also prevented by the AMPA/KA antagonist LY293558 [88]. Similar results were obtained with animal studies that demonstrated that formalin-induced behaviours [75] but not acute physiological nociceptive responses [89] are reduced by the GluR5-selective antagonist, LY382884. Recent studies in spinal cord slices have identified kainate receptor-mediated responses (EPSPs) restricted to synapses formed by high threshold nociceptive and thermoceptive afferent fibres.…”

In vitro and in vivo studies in rats with LY293558 suggest AMPA/kainate receptor blockade as a novel potential mechanism for the therapeutic treatment of anxiety disorders

“…As these receptors have been shown pharmacologically (Procter et al 1998;Simmons et al 1998;Blackburn-Munro et al 2004;Palecek et al 2004), clinically (Gilron et al 2000), and through the use of transgenic mice (Ko et al 2005; however, see Youn and Randic 2004) to be related to the control of pain pathways, the question of whether the anxiolytic-like effects of LY293558 are mediated through an analgesic effect can be raised. Although specific measurements of reactivity or detection thresholds for the electric foot current used as a punisher in the present experiment were not established, ample evidence has long been available to document that analgesia per se is not a driver of anxiolyticlike activity in the punishment assay used here (c.f., Kelleher and Morse 1968).…”

Altered Behavioral Responses to Noxious Stimuli and Fear in Glutamate Receptor 5 (GluR5)- or GluR6-Deficient Mice

“…In the periphery and spinal cord, KARs play an important role in sensory transmission. KARs are located on sensory afferent fibers and dorsal root ganglion (DRG) cells (Partin et al, 1993;Tolle et al, 1993;Procter et al, 1998;Hwang et al, 2001;Kerchner et al, 2001b. In the spinal cord, they are located on the postsynaptic membrane of dorsal horn neurons and contribute to synaptic responses to high-threshold primary afferent fiber stimulation (Li et al, 1999).…”