Peripheral antinociceptive effect of 2-arachidonoyl-glycerol and its interaction with endomorphin-1 in arthritic rat ankle joints

Abstract

1. Both cannabinoid and opioid receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the effect of endogenous ligands at these receptors is poorly understood. Our goal was to determine the antinociceptive potency of the endogenous cannabinoid 2-arachidonoyl-glycerol (2-AG), and its interaction with endomorphin-1 (EM1) at joint level in the rat inflammation model. 2. Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/30 microL) into the tibiotarsal joint of the right hind leg. The mechanical threshold was assessed by von Frey filaments. 2-AG (3-200 microg), EM1 (100-300 microg) and their combinations in a fixed-dose ratio (1 : 10) were given into the inflamed joint, and the threshold was determined repeatedly for 105 min after the drug administrations. 3. Both ligands produced dose-dependent anti-hyperalgesia, and the highest doses caused prolonged effects, but they did not influence the degree of oedema and the withdrawal threshold at the non-inflamed side. EM1 had lower potency compared to 2-AG (ED(25): 233 (CI: 198-268) microg and 126 (CI: 88-162) microg, respectively; P < 0.05). The effects of EM1 and 2-AG were prevented by mu-opioid and cannabinoid 1 receptor antagonists, respectively. The ED(25) value for the combination (98 (CI: 80-112) microg) did not differ significantly from the value of 2-AG; however, the largest dose combination produced a significantly higher effect than the ligands by themselves. 4. Our data showed that 2-AG was an effective antinociceptive ligand at joint level, and its combination with EM1 produced long-lasting, effective antinociception.

Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain

“…Injection of 2-AG near the site of injury decreases nocifensive behavior in rat models of inflammatory [13,14] and neuropathic pain [15]. Whether the anti-hyperalgesic effect of 2-AG in the periphery is mediated by CB1 or CB2 receptors is dependent on the model and the behavioral assay: The effect of 2-AG in the formalin model of inflammatory pain is selectively blocked by local administration of a CB2 receptor antagonist [13], but both CB1 and CB2 receptor antagonists block the anti-allodynic effect of 2-AG in a model of neuropathic pain [15].…”

Cannabinoids and muscular pain. Effectiveness of the local administration in rat

“…CBs induce pain relief in a variety of animal models (Richardson, 2000); their antinociceptive efficacy has been demonstrated in several models of nociceptive, inflammatory and neuropathic pain (Pascual et al, 2005;Walker and Hohmann, 2005;Karst et al, 2010), and also endocannabinoids have shown to exert and antinociceptive effect in osteoarticular pain models (Mecs et al, 2010). Regarding their clinical use in pathological processes that course with musculoskeletal disorders, Sativex® (D 9 -tetrahydrocannabinol and cannabidiol) has been recently commercialized to improve the spasticity and pain of patients with multiple sclerosis (Karst et al, 2010;Sastre-Garriga et al, 2011).…”

Review, Analyse und Kausalitätsprüfung von Cannabis-based Medicine und Palmitoylethanolamid als Analgetika bei Rheumaschmerzen

“…13 21,44,45 Vor allem aber in pathologischen Zuständen scheint das Endocannabinoidsystem wichtige Funktionen zu übernehmen. In präklinischen Studien konnte eine Abschwächung von peripheren und viszeralen Entzündungsreaktionen durch AEA und 2-AG nachgewiesen [46][47][48] sowie das Herbeiführen einer Schmerzminderung in bestimmten Stresssituation, der sog. stressinduzierten Analgesie, festgestellt werden.…”