James G Kelly

University of Glasgow, Glasgow, Scotland, United Kingdom

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Publications (3)16.31 Total impact

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    ABSTRACT: Tissue damage during surgery can induce 'central sensitization' and the development of pain and hyperalgesia post-operatively. Metabotropic glutamate receptors (mGluRs) contribute to nociception, inflammatory pain and hyperalgesia. This study characterized the temporal expression of group I (mGluR(1), mGluR(5)) and II (mGluR(2), mGluR(3)) mGluRs in spinal cord following abdominal surgery. Lumbar spinal cord was recovered from adult sheep euthanased 5 h, 1, 2, 3 and 6 days after undergoing a midline laparotomy, and processed for mGluR mRNA (real-time PCR, in situ hybridization) and protein (Western blotting). mGluR(5) mRNA was up-regulated 5 h and 1 day post-surgery in laminae I-II of the spinal cord dorsal horn. mGluR(5) protein was increased 1 day post-surgery. A delayed induction of mGluR(2) and mGluR(3) mRNAs and mGluR(2/3) protein occurred in spinal cord 3 days after surgery. By 6 days, mGluR(2) mRNA levels had returned to normal, however, mGluR(3) mRNA and mGluR(2/3) protein remained elevated. No change was detected in mGluR(1). These results demonstrate that mGluRs are differentially regulated following surgery and support a link between mGluR-mediated activity and post-surgical pain.
    No preview · Article · Aug 2004 · Pain
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    ABSTRACT: Evidence from experimental pain research has revealed that metabotropic glutamate receptors (mGluRs) play a pivotal role in nociceptive processing, inflammatory pain and hyperalgesia. The aim of this study was to characterise expression of group I and II mGluRs in spinal cord in a model of naturally occurring persistent inflammation (sheep with unilateral lameness due to inflammation of the digital tissues of the feet, estimated to have been affected by the condition for >2 weeks) and an experimental model of acute inflammation (injection of intradermal carrageenan into lower forelimb in sheep). Animals with unilateral clinical inflammation displayed significant mechanical hyperalgesia on the affected limb. Carrageenan treatment produced significant bilateral limb mechanical hyperalgesia 3 h post-injection. Up-regulation of mGluR(3) and mGluR(5) mRNA was observed in ipsilateral spinal cord recovered from clinically lame animals, restricted to laminae II-V and I-II, respectively. Western blot analyses of protein extracts revealed a bilateral increase in mGluR(2/3) and mGluR(5). No change was detected in spinal cord mGluR(1) or mGluR(2) mRNA. There was no change in mGluR(1,2,3,5) subtype mRNA or proteins in spinal cord recovered from animals 3 h post-carrageenan. These results demonstrate for the first time that mGluR subtypes are differentially expressed in spinal cord dorsal horn in response to persistent inflammation, and suggest that mGluR activity may be involved in mediating altered behaviours associated with clinical inflammatory pain.
    No preview · Article · Jan 2004 · Pain
  • Sharron Dolan · James G Kelly · Marie Huan · Andrea M Nolan
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    ABSTRACT: Surgery induces pain and hyperalgesia postoperatively. The products of cyclooxygenases and nitric oxide synthase (NOS) have been implicated in the development of inflammatory pain and hyperalgesia experimentally, and the use of drugs clinically that modify cyclooxygenase activity has been advocated in the management of perioperative pain. However, regulation of these enzymes following surgery has not been studied. Adult female sheep (n = 12) undergoing a midline laparotomy for collection of ova were used in this study. Lumbar and cervical spinal cord tissue was collected from animals euthanized 1 day and 6 or 7 days after surgery and processed for cyclooxygenase (cyclooxygenase-1 and cyclooxygenase-2), neuronal NOS mRNA expression using reverse-transcription polymerase chain reaction and hybridization. Tissues were also processed for NADPH-diaphorase staining and cyclooxygenase-1 and cyclooxygenase-2 protein expression by immunohistochemistry and Western blotting. No alteration in cyclooxygenase-1 or cyclooxygenase-2 mRNA or protein concentrations were detected in spinal cord by reverse-transcription polymerase chain reaction and Western blotting, respectively, at 1 day or 6 or 7 days after surgery. However, using techniques that localize mRNA and protein expression ( hybridization and immunohistochemistry, respectively), increases in cyclooxygenase-2 were identified in lamina V dorsal horn neurons in lumbar spinal cord 1 day after surgery. A significant increase in neuronal NOS mRNA was observed in lumbar spinal cord 1 day after surgery, localized to laminae I-II and lamina V neurons, which returned to baseline concentrations by 6 to 7 days. NADPH-diaphorase staining was significantly increased in laminae I-II in lumbar spinal cord 1 day after surgery but not after 6 to 7 days. Spinal cyclooxygenase and neuronal NOS pathways are differentially altered following surgical inflammation. The early and transient nature of these changes suggests that these enzymes are implicated in postoperative pain and hypersensitivity.
    No preview · Article · Feb 2003 · Anesthesiology