1 The responses of wide dynamic range spinal dorsal horn neurones to noxious mechanical stimulation of the ankle or knee joint were tested before and after spinal administration of the non-selective cyclooxygenase (COX) inhibitors, indomethacin and meclofenamic acid. Neither of these drugs altered the responses of these neurones to noxious mechanical stimulation. 2 Wind-up of a spinal nociceptive re¯ex evoked by electrical stimulation of the sural nerve at C-®bre strength was dose-dependently inhibited by intravenous administration of indomethacin, a non-selective COX inhibitor, and SC58125, a selective COX-2 inhibitor. Intrathecal administration of indomethacin also reduced the wind-up of this nociceptive re¯ex. 3 Western blot analysis of proteins extracted from normal rat spinal cord revealed the presence of both cyclo-oxygenase (COX)-1 and COX-2 proteins. 4 Immunocytochemistry of sections of normal rat spinal cord with speci®c COX-1 antiserum revealed little speci®c COX-1-like immunoreactivity in the grey matter. With the same antiserum, intense COX-1-like immunoreactivity was observed in the cytoplasm, nuclear membrane and axonal processes of small to medium sized (51000 mm 2 ) dorsal root ganglion (DRG) cell bodies. 5 Immunocytochemistry of sections of normal rat spinal cord incubated with speci®c COX-2 antiserum showed intense COX-2-like immunoreactivity (COX-2-li) in the super®cial dorsal horn of the spinal cord (laminae I and II) and around the central canal (lamina X). COX-2-li was also observed in some neurones in deep dorsal horn and in individual motor neurones in ventral horn. COX-2-li was not observed in the cell bodies of DRG. 6 Superfusion of the lumbar spinal cord of normal rats with arti®cial CSF and subsequent radioimmunoassay revealed the presence of prostaglandin D 2 (PGD 2 )5PGE 2 , but not PGI 2 (determined by measurement of the stable metabolite, 6-keto-PGF 1a ) or PGF 2a . 7 These data suggest that eicosanoids synthesized by an active COX pathway in the spinal cord of normal animals may contribute to nociceptive processing, but only when the spinal cord neurones are rendered hyperexcitable following C-®bre stimulation. Selective inhibition of one or both of the COX isoforms in normal animals may represent a novel target for spinal analgesia.
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