A New Mechanical Method for Measuring Rat Paw Edema

Petricevic, M; Wanek, Kathy; Denko, Charles W.

doi:10.1159/000136761

Cited by 10 publications

(6 citation statements)

References 2 publications

(6 reference statements)

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“…At the end of the formalin test, maximal paw thickness was measured at the base of the right hind paw using a digital micrometer (Mitutoyo Corporation, Aurora, IL, USA) with a resolution of 0.001 mm (Petricevic et al ., 1978; Guindon et al ., 2007a).…”

Section: Methodsmentioning

confidence: 99%

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

Guindon

Guijarro

Piomelli

et al. 2011

British J Pharmacology

104

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The endocannabinoid 2-arachidonoylglycerol (2-AG) is degraded primarily by monoacylglycerol lipase (MGL). We compared peripheral antinociceptive effects of JZL184, a novel irreversible MGL inhibitor, with the reversible MGL-preferring inhibitor URB602 and exogenous 2-AG in rats. EXPERIMENTAL APPROACHNociception in the formalin test was assessed in groups receiving dorsal paw injections of vehicle, JZL184 (0.001-300 mg), URB602 (0.001-600 mg), 2-AG (ED50), 2-AG + JZL184 (at their ED50), 2-AG + URB602 (at their ED50), AM251 (80 mg), AM251 + JZL184 (10 mg), AM630 (25 mg) or AM630 + JZL184 (10 mg). Effects of MGL inhibitors on endocannabinoid accumulation and on activities of endocannabinoid-metabolizing enzymes were assessed. KEY RESULTSIntra-paw administration of JZL184, URB602 and 2-AG suppressed early and late phases of formalin pain. JZL184 and URB602 acted through a common mechanism. JZL184 (ED50 Phase 1: 0.06 Ϯ 0.028; Phase 2: 0.03 Ϯ 0.011 mg) produced greater antinociception than URB602 (ED50 Phase 1: 120 Ϯ 51.3; Phase 2: 66 Ϯ 23.9 mg) or 2-AG. Both MGL inhibitors produced additive antinociceptive effects when combined with 2-AG. Antinociceptive effects of JZL184, like those of URB602, were blocked by cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) antagonists. JZL184 suppressed MGL but not fatty-acid amide hydrolase or N-arachidonoyl-phosphatidylethanolamine phospholipase D activities ex vivo. URB602 increased hind paw 2-AG without altering anandamide levels. CONCLUSIONS AND IMPLICATIONSMGL inhibitors suppressed formalin-induced pain through peripheral CB1 and CB2 receptor mechanisms. MGL inhibition increased paw skin 2-AG accumulation to mediate these effects. MGL represents a target for the treatment of inflammatory pain.

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Section: Methodsmentioning

confidence: 99%

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

Guindon

Guijarro

Piomelli

et al. 2011

British J Pharmacology

104

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“…At the end of the formalin test, paw oedema was measured at the base of the right hind paw using a digital micrometer (Mitutoyo Corporation, Aurora, IL, USA) with an instrumental error of ±(maximum measuring length/75 μ m) and a resolution of 0.001 mm ( Petricevic et al ., 1978 ; Nackley et al ., 2003b ; Ghilardi et al ., 2004 ; Guindon et al ., 2006a , 2006b ).…”

Section: Methodsmentioning

confidence: 99%

The antinociceptive effects of intraplantar injections of 2‐arachidonoyl glycerol are mediated by cannabinoid CB₂ receptors

Guindon

Desroches

Beaulieu

2007

British J Pharmacology

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Background and purpose: 2-arachidonoyl glycerol (2-AG) is an endogenous cannabinoid with central antinociceptive properties. Its degradation is catalysed by monoacylglycerol lipase (MGL) whose activity is inhibited by URB602, a new synthetic compound. The peripheral antinociceptive effects of 2-AG and URB602 in an inflammatory model of pain are not yet determined. We have evaluated these effects with and without the cannabinoid CB 1 (AM251) and CB 2 (AM630) receptor antagonists. Experimental approach: Inflammation was induced in rat hind paws by intraplantar injection of formalin. Nociception was assessed behaviourally over the next 60 min, in 19 experimental groups: (1) control; (2-6) 2-AG (0.01-100 mg); (7) AM251 (80 mg); (8) AM251 þ 2-AG (10 mg); (9) AM630 (25 mg); (10) AM630 þ 2-AG (10 mg); (11-16) URB602 (0.1-500 mg); (17) 2-AG þ URB602 (ED 50 ); (18) AM251 þ URB602 (ED 50 ); (19) AM630 þ URB602 (ED 50 ). Drugs were injected s.c. in the dorsal surface of the hind paw (50 ml), 15 min before formalin injection into the same paw. Key results: 2-AG and URB602 produced dose-dependent antinociceptive effects for the late phases of the formalin test with ED 50 of 0.6570.455 mg and 68714.3 mg, respectively. Their combination at ED 50 doses produced an additive antinociceptive effect. These effects were inhibited by AM630 but not by AM251 for 2-AG and by the two cannabinoid antagonists for URB602. Conclusions and implications: Locally injected 2-AG and URB602 decreased pain behaviour in a dose-dependent manner in an inflammatory model of pain. The antinociceptive effect of 2-AG was mediated by the CB 2 receptor.

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“…Signs of inflammation usually developed in about 30 minutes following injection of the cryoglobulin; the most constant feature being swelling. Swelling in the inflamed foot was quantified by a mechanical spring device which measured the diameter of the foot [13].…”

Section: Methodsmentioning

confidence: 99%

Cryoglobulin-induced inflammation

Denko

1985

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Inflammation of the rat footpad followed injection of cryoglobulin in crystalline form (Type I) and injection of cryoglobulin in solution (Type II). Rats deficient in essential fatty acids responded with diminished swelling which corrected to normal levels by addition of prostaglandin E1 suggesting that this reaction is prostaglandin mediated. Addition of bradykinin produced no effect. Aggregated cryoglobulin proved more inflammogenic than non-aggregated cryoglobulin. Pre-treatment with choline salicylate and colchicine reduced swelling while pre-treatment with dipyridamole increased edema following cryoglobulin inoculation. Cryoglobulin is considered to be an acute phase reactant in inflammation.

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A New Mechanical Method for Measuring Rat Paw Edema

Cited by 10 publications

References 2 publications

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

The antinociceptive effects of intraplantar injections of 2‐arachidonoyl glycerol are mediated by cannabinoid CB₂ receptors

Cryoglobulin-induced inflammation

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A New Mechanical Method for Measuring Rat Paw Edema

Cited by 10 publications

References 2 publications

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a rat model of inflammatory pain

The antinociceptive effects of intraplantar injections of 2‐arachidonoyl glycerol are mediated by cannabinoid CB2 receptors

Cryoglobulin-induced inflammation

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The antinociceptive effects of intraplantar injections of 2‐arachidonoyl glycerol are mediated by cannabinoid CB₂ receptors