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Peripheral orthopaedic surgery induces a profound inflammatory response. This includes a substantial increase in cytokines and, especially, in the level of interleukin (IL)-1β in the hippocampus, which has been shown to impair hippocampal-dependent memory in mice. We have employed two tests of contextual remote memory to demonstrate that the inflammatory response to surgical insult in mice also results in impairment of remote memory associated with prefrontal cortex (PFC). We have also found that, under the conditions presented in the social interaction test, peripheral orthopaedic surgery does not increase anxiety-like behaviour in our animal model. Although such surgery induces an increase in the level of IL-1β in the hippocampus, it fails to do so in the PFC. Peripheral orthopaedic surgery also results in a reduction in the level of hippocampal brain-derived neurotrophic factor (BDNF) and this may contribute, in part, to the memory impairment found after such surgery. Our data suggest that a reduction in the level of hippocampal BDNF and an increase in the level of hippocampal IL-1β following surgery may affect the transference of fear memory in the mouse brain., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Activation of members of the family of enzymes known as extracellular signal-regulated kinases (ERKs) is now known to be involved in the development and/or maintenance of the pain associated with many inflammatory conditions, such as herniated spinal disc pain, chronic inflammatory articular pain, and the pain associated with bladder inflammation. Moreover, ERKs are implicated in the development of neuropathic pain signs in animals which are subjected to the lumbar 5 spinal nerve ligation model and the chronic constriction injury model of neuropathic pain. The position has now been reached where all scientists working on pain subjects ought to be aware of the importance of ERKs, if only because certain of these enzymes are increasingly employed as experimental markers of nociceptive processing. Here, we introduce the reader, first, to the intracellular context in which these enzymes function. Thereafter, we consider the involvement of ERKs in mediating nociceptive signalling to the brain resulting from noxious stimuli at the periphery which will be interpreted by the brain as pain of peripheral origin., (Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.)

Clinically relevant concentrations of isoflurane or sevoflurane sensitize transient receptor potential vanilloid type 1 to several of its activators, including capsaicin. It has, moreover, been suggested these volatile general anaesthetics may augment nociceptive signalling arising from surgical procedures and thereby contribute to post-operative pain. To investigate this suggestion, we have studied intraplantar capsaicin injection-induced phosphorylation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons (which is a recognized marker of spinal nociceptive processing) in rat during isoflurane or sevoflurane anaesthesia after 60 min under anaesthesia. Control animals were anaesthetized with pentobarbital (which of itself does not activate extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons). Unilateral intraplantar capsaicin injection in control animals evoked extracellular signal-regulated kinase 1/2 phosphorylation in a group of neurons in lamina I and lamina II of the ipsilateral spinal dorsal horn in a somatotopically appropriate area. In contrast, both anaesthetic gases (given for 60 min and without subsequent capsaicin injection) induced extracellular signal-regulated kinase 1/2 activation in a different group of mainly lamina I neurons bilaterally. The total number of spinal dorsal horn neurons labelled on the ipliateral side following capsaicin injection into the isoflurane-, or sevoflurane-, anaesthetized animals was significantly less than that produced by capsaicin alone. Further, capsaicin injection into isoflurane-, or sevoflurane-, anaesthetized animals reduced extracellular signal-regulated kinase 1/2 phosphorylation induced by the gases alone on both sides. These findings do not support the suggestion that isoflurane-, or sevoflurane-, induced sensitization of transient receptor potential vanilloid type 1 by capsaicin, or other agonist, is translated into induction of spinal nociceptive processing and consequential pain sensation., (Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)