2011
DOI: 10.1016/j.pain.2010.11.025
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Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis

Abstract: The present study examined whether enhancement of endogenous cannabinoid levels by administration of the fatty acid amide hydrolase inhibitor URB597 could modulate joint nociception in 2 rodent models of osteoarthritis (OA). OA-like changes were induced in male Wistar rats by intra-articular injection of monoiodoacetate, while Dunkin-Hartley guinea pigs (age 9-12 months) develop OA naturally and were used as a model of spontaneous OA. Joint nociception was measured by recording electrophysiologically from knee… Show more

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Cited by 65 publications
(53 citation statements)
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“…The hypothesis jpet.aspetjournals.org that FAAH inhibition can boost the analgesic effect of endocannabinoids is supported by the finding that FAAH knockout mice (Cravatt et al, 2001) display hypoalgesic phenotype, as well as by the analgesic effects of the FAAH inhibitors OL135 and URB597 in various rodent models of nociception (Lichtman et al, 2004b;Chang et al, 2006;Jhaveri et al, 2006;Palmer et al, 2008;Kinsey et al, 2009). The antinociceptive potential of FAAH inhibitors has also been recently underlined in two rodent models of osteoarthritis (Schuelert et al, 2011), thus corroborating the idea that endocannabinoid enhancers may exert anti-inflammatory effects by reducing levels of proinflammatory cytokines such as interleukin-1␤ and tumor necrosis factor ␣ (Naidu et al, 2010). However, as for the analgesic effects of FAAH inhibition on neuropathic pain, the results described are not always consistent.…”
Section: Discussionmentioning
confidence: 85%
“…The hypothesis jpet.aspetjournals.org that FAAH inhibition can boost the analgesic effect of endocannabinoids is supported by the finding that FAAH knockout mice (Cravatt et al, 2001) display hypoalgesic phenotype, as well as by the analgesic effects of the FAAH inhibitors OL135 and URB597 in various rodent models of nociception (Lichtman et al, 2004b;Chang et al, 2006;Jhaveri et al, 2006;Palmer et al, 2008;Kinsey et al, 2009). The antinociceptive potential of FAAH inhibitors has also been recently underlined in two rodent models of osteoarthritis (Schuelert et al, 2011), thus corroborating the idea that endocannabinoid enhancers may exert anti-inflammatory effects by reducing levels of proinflammatory cytokines such as interleukin-1␤ and tumor necrosis factor ␣ (Naidu et al, 2010). However, as for the analgesic effects of FAAH inhibition on neuropathic pain, the results described are not always consistent.…”
Section: Discussionmentioning
confidence: 85%
“…FAAH is one of the main enzymes known to break down the endogenous cannabinoid, anandamide, as well as noncannabinoid fatty acid amides (Cravatt et al 2001). FAAH inhibition has been found to elicit antinociceptive effects in animal models of arthritis (Schuelert et al 2011). In spite of promising preclinical data, the single clinical trial examining a FAAH inhibitor (PF-04457845) did not find a significant improvement in pain associated with osteoarthritis of the knee (N=69/74).…”
Section: Faah Inhibitormentioning
confidence: 98%
“…2,66 TRPV1 antagonists block pain sensitivity, 12,16,31,32 and TRPV1 polymorphisms are associated with an increased risk of symptomatic knee OA, 74 whereas the inhibition of endocannabinoid inactivation by, eg, fatty acid amide hydrolase (FAAH) is effective for chronic and inflammatory pain. 1,41,65,66 Therefore, both might be attractive pharmacological targets for the treatment of OA pain. Despite the claimed therapeutic potential of TRPV1 antagonists, only a few candidates have progressed through clinical trials because of unpredicted secondary effects such as hyperthermia.…”
Section: Introductionmentioning
confidence: 99%