Pharmacological characterisation of acid-induced muscle allodynia in rats.
Previous studies have shown that repeated injections of acidic saline, given into the lateral gastrocnemius muscle of rats, results in a bilateral reduction in withdrawal threshold to tactile stimulation of the hindpaws. We have now characterised this model of muscoskeletal pain pharmacologically, by evaluating the antinociceptive effects of various analgesics after systemic administration. The micro-opioid receptor agonist morphine (3 and 6 mg/kg) produced a particularly prolonged antiallodynic effect. The glutamate receptor antagonists ([8-methyl-5-(4-(N,N-dimethylsulfamoyl)phenyl)-6,7,8,9,-tetrahydro-1H-pyrrolo[3,2-h]-iso-quinoline-2,3-dione-3-O-(4-hydroxybutyric acid-2-yl)oxime] NS1209 and ketamine (6 and 15 mg/kg, respectively), the KCNQ K(+) channel openers retigabine and flupirtine (10 and 20 mg/kg, respectively) and the Na(+) channel blocker mexiletine (37.5 mg/kg) also significantly increased paw withdrawal threshold, although to a lesser degree than morphine. In contrast, the anticonvulsant lamotrigine (30 mg/kg), the cyclooxygenase-2 inhibitor carprofen (15 mg/kg) and the benzodiazepine diazepam (3 mg/kg) were ineffective. All antinociceptive effects were observed at nonataxic doses as determined by the rotarod test. These results suggest that in this model, muscle-mediated pain can be alleviated by various analgesics with differing mechanisms of action, and that once established ongoing inflammation does not appear to contribute to this process.
Nielsen
Alexander Norup
AN
Department of Pharmacology, NeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark. ann@neurosearch.dk
Mathiesen
Claus
C
Blackburn-Munro
Gordon
G
D000143:Acids; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001259:Ataxia / Q000139:chemically induced / Q000473:pathology; D002227:Carbazoles / Q000627:therapeutic use; D002908:Chronic Disease; D003080:Cold Temperature; D003975:Diazepam / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D007839:Functional Laterality / Q000502:physiology; D018757:GABA Modulators / Q000627:therapeutic use; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009135:Muscular Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects
D000143:Acids; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D015221:Potassium Channels; D017470:Receptors, Glutamate; D026941:Sodium Channel Blockers; D009020:Morphine; C007005:carprofen; D003975:Diazepam