Effects of intrathecal morphine, baclofen, clonidine and R-PIA on the acute allodynia-like behaviours after spinal cord ischaemia in rats.
The present study assessed the efficacy and potency of intrathecal (i.t.) administration of the opiate morphine, the gamma-aminobutyric acid-B (GABA(B)) receptor agonist baclofen, the alpha2-adrenoceptor agonist clonidine and the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) on the acute allodynia-like behaviour after photochemically induced spinal cord injury (SCI) in rats. Rats displaying allodynia-like behaviours to brushing, von Frey hairs and cold stimulation 1-2 days after photochemically induced SCI were studied. In a cumulative dose regime, morphine (0.1-10 micrcog), baclofen (0.1-1 microg), clonidine (0.1-10 microg) and R-PIA (0.01-10 nmol) were administered i.t. through an implanted catheter at the lumbar spinal cord. All tested drugs dose-dependently reduced the brushing, von Frey hairs and cold stimulation-induced allodynia-like behaviour. No increase in adverse effects such as motor deficits was found for morphine, clonidine and R-PIA. There was a slight increase in motor impairments at the highest dose of baclofen. For the mechanical allodynia, morphine appeared to be most effective, whereas baclofen, clonidine and R-PIA only provided a partial alleviation. For the cold allodynia, morphine and baclofen were more effective than clonidine and R-PIA. In relieving acute mechanical and cold allodynia-like behaviours in rats 1-2 days after SCI, i.t. morphine and baclofen were superior to clonidine and R-PIA.
von Heijne
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Karolinska Institutet, Pediatric Anesthesia and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden. Margaret.von.heijne@karo.ki.se
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Sollevi
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D007278:Injections, Spinal; D007511:Ischemia / Q000150:complications / Q000188:drug therapy; D009020:Morphine / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013116:Spinal Cord / Q000098:blood supply / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D018755:GABA Agonists; D018696:Neuroprotective Agents; C047235:N-(1-methyl-2-phenylethyl)adenosine; D012965:Sodium Chloride; D009020:Morphine; D001418:Baclofen; D000241:Adenosine; D003000:Clonidine