Pain
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The present studies assessed the role of G(zalpha) and G(oalpha) in spinal alpha(2) adrenergic receptor agonist-induced antinociception, as well as in antinociceptive synergism between spinal morphine and clonidine. Mice were pretreated with a single intrathecal (i.t.) injection of artificial cerebrospinal fluid (ACSF), antisense oligodeoxynucleotide(s) (ODN) directed against G(zalpha) or G(oalpha), or nonsense ODN. After 48 h, the antinociceptive effects expressed as per cent maximal possible effect (% MPE) of either i.t. morphine alone, clonidine alone or coadministered morphine plus clonidine, were evaluated in the tail flick test. ⋯ Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO)- (mu opioid receptor agonist) and U50-488 (kappa opioid receptor agonist) -induced antinociception. Pretreatment with antisense ODN to G(oalpha) attenuated both morphine and clonidine induced antinociception and did not affect synergism between the agonists. These results suggest that spinal G(o)alpha mediates antinociception produced by both clonidine and morphine while G(zalpha) mediates alpha(2) adrenergic and delta opioid receptor mediated antinociception, but not antinociception produced by mu or kappa opioid agonists.
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We have recently reported that injury to a lumbar root in a rat model of radiculopathy produces spinal glial activation associated with elevated proinflammatory cytokines. Based on our hypothesis that central neuroinflammatory processes may manifest clinically as radicular pain, we undertook pharmacological intervention using the immunosuppressive agent methotrexate (MTX). The L5 lumbar spinal root (central to the dorsal root ganglia) was exposed unilaterally and loosely constricted with chromic gut. ⋯ However, spinal expression of MHC II was markedly reduced in the MTX treated group as compared with the saline treated group. The exact mechanism of action of MTX in attenuating mechanical allodynia has not yet been elucidated. The present results indicate that MTX administration may offer a new treatment modality for radicular pain with or without disc herniation as well as directing new research into the development of novel immunomodulators for the treatment of chronic neuropathic and radicular pain.
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Mechanical allodynia- and hyperalgesia-like behavior which develops in rats after L5 spinal nerve lesion has been suggested to be due to ectopic activity in the lesioned afferent neurons originating at the lesion site and/or in the dorsal root ganglion because it is eliminated by section of the dorsal root. Here we reevaluated the effect of a dorsal rhizotomy in rats after L5 spinal nerve lesion. Using calibrated von Frey hairs, paw withdrawal threshold to single stimuli and paw withdrawal incidence to repetitive stimulation were tested before and after nerve section. ⋯ These results challenge the widely accepted idea that neuropathic pain behavior developing after spinal nerve lesion is dependent on ectopic activity in the lesioned afferent neurons. However, the present results do not rule out the possibility that after the two nerve lesions the mechanisms generating neuropathic pain behavior are different. After dorsal rhizotomy neuropathic pain behavior may be related to deafferentation whereas after spinal nerve lesion it may be caused by ectopic activity.
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Little is known about the epidemiology of pain in children. We studied the prevalence of pain in Dutch children aged from 0 to 18 years in the open population, and the relationship with age, gender and pain parameters. A random sample of 1300 children aged 0-3 years was taken from the register of population in Rotterdam, The Netherlands. ⋯ The intensity of pain was higher in the case of chronic pain (P<0. 001) and multiple pains (P<0.001), and for chronic pain the intensity was higher for girls (P<0.001). These findings indicate that chronic pain is a common complaint in childhood and adolescence. In particular, the high prevalence of severe chronic pain and multiple pain in girls aged 12 years and over calls for follow-up investigations documenting the various bio-psycho-social factors related to this pain.
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Case Reports
Spinal cord stimulation: a possible therapeutic alternative for chronic mesenteric ischaemia.
A 78-year-old male patient had chronic, unrelieved abdominal pain due to mesenteric ischaemia. Unsuccessful pharmacological approaches included oral morphine plus coadjuvants as well as a sympathetic celiac plexus block which gave pain relief that lasted for 72 h. In order to obtain long-lasting relief, a trial epidural stimulating electrode was implanted after obtaining informed consent and Ethical Committee approval. ⋯ Thereafter, a spinal cord stimulator was implanted. At the time of writing, 11 months after implantation, the degree of analgesia is complete. We believe that spinal cord stimulation may represent an alternative approach in controlling pain due to mesenteric ischaemia.