Research paperA peripheral cannabinoid mechanism suppresses spinal fos protein expression and pain behavior in a rat model of inflammation
Section snippets
Subjects
One hundred and forty six adult male Sprague–Dawley rats (Harlan, Indianapolis, IN, USA), weighing 275–350 g, were used in these experiments. All procedures were approved by the University of Georgia Animal Care and Use Committee and followed the guidelines for the treatment of animals of the International Association for the Study of Pain (Zimmermann, 1983). All efforts were made to minimize the number of animals and their suffering.
Drugs and chemicals
Lambda carrageenan and WIN55,212-2 were obtained from Sigma
Behavioral studies
In all studies, the threshold and frequency of paw withdrawal elicited in response to the von Frey monofilaments did not differ between groups prior to i.p.l. administration of carrageenan. Carrageenan lowered the threshold (P<0.0002 for each experiment) and increased the frequency (P<0.002 for each experiment) of paw withdrawal in response to stimulation with von Frey monofilaments.
Experiment 1: Effects of local and systemic administration of WIN55,212-2 on the development of carrageenan-evoked allodynia and mechanical hyperalgesia
In experiment 1, the threshold for paw withdrawal was higher in groups receiving the cannabinoid agonist
Discussion
The present studies demonstrate that systemically inactive doses of cannabinoids suppress the development of inflammation-evoked neuronal activity in rat lumbar spinal cord in vivo through a peripheral mechanism. Administration (i.p.l.) of the selective cannabinoid agonist WIN55,212-2 suppressed carrageenan-evoked allodynia and hyperalgesia as well as carrageenan-evoked Fos protein expression in the rat lumbar dorsal horn. These effects were mediated by a peripheral mechanism because the
Conclusions
In conclusion, the present studies provide direct evidence that systemically inactive doses of cannabinoids suppress the development of inflammation-evoked neuronal activity in rat lumbar spinal cord in vivo through a peripheral mechanism. These data are consistent with the ability of local but not systemic injections of a cannabinoid agonist to attenuate the development of behavioral sensitization evoked by punctate mechanical stimuli in the carrageenan model of inflammation. Fos protein
Acknowledgements
Supported by UGARF and DA014265 (AGH). The authors are grateful to Mark H. Neely for assistance with data analysis.
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