Behavioural pharmacology
-
Behavioural pharmacology · Apr 2014
Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models.
Thermal sensitivity is an essential characteristic of some painful states, including oxaliplatin-induced neuropathy. The thermal place preference test (TPPT) was designed to finely assess thermal sensitivity in rodents. The TPPT monitors the time spent by unrestrained rodents on a test plate at fixed temperatures (5-50°C) compared with an adjacent reference plate at a neutral temperature (25°C). ⋯ When compared with control animals, oxaliplatin-treated rats showed thermal hypersensitivity at 12, 20 and 35°C, and carrageenan-treated rats showed thermal hypersensitivity at 15 and 45°C. Duloxetine (2.5 mg/kg, intraperitoneal) reversed oxaliplatin-induced cold hypersensitivity (20°C) and morphine (1 mg/kg, intravenous) reversed carrageenan-induced heat hypersensitivity (45°C). We conclude that the TPPT enables a fine-grained assessment of thermal sensitivity that is relevant to the pathophysiological exploration of animal pain models and to the pharmacological assessment of analgesic drugs.
-
Behavioural pharmacology · Apr 2014
Analgesic efficacy of small-molecule angiotensin II type 2 receptor antagonists in a rat model of antiretroviral toxic polyneuropathy.
Individuals infected with the HIV and taking certain antiretroviral drugs to suppress viral replication have a high prevalence of neuropathic pain that is not alleviated by analgesic/adjuvant drugs that are often efficacious for the relief of other types of neuropathic pain. There is therefore a great need for new analgesics to alleviate the pain of antiretroviral toxic neuropathy (ATN). Small-molecule angiotensin II type 2 receptor (AT2R) antagonists, with ≥1000-fold selectivity over the angiotensin II type 1 receptor, produced analgesia in the chronic constriction injury of the sciatic nerve rat model of peripheral nerve trauma. ⋯ Single intraperitoneal bolus doses of EMA200 (0.3-10 mg/kg) induced dose-dependent analgesia in ddC-rats; the mean ED50 was 3.2 mg/kg. Twice-daily intraperitoneal administration of EMA300 at 30 mg/kg to ddC-rats for 3 days produced significant analgesia on days 2 and 3 of the treatment period. Therefore, small-molecule AT2R antagonists should be investigated further as novel analgesics for the relief of ATN.
-
Behavioural pharmacology · Apr 2014
Effects of the fatty acid amide hydrolase inhibitor URB597 on pain-stimulated and pain-depressed behavior in rats.
Cannabinoid receptor (CBR) agonists produce antinociception in conventional preclinical assays of pain-stimulated behavior but are not effective in preclinical assays of pain-depressed behavior. Fatty acid amide hydrolase (FAAH) inhibitors increase physiological levels of the endocannabinoid anandamide, which may confer improved efficacy and safety relative to direct CBR agonists. To further evaluate FAAH inhibitors as candidate analgesics, this study assessed the effects of the FAAH inhibitor URB597 in assays of acute pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats. ⋯ Conversely, in the assay of acid-depressed intracranial self-stimulation, URB597 produced a delayed, partial and non-CBR-mediated antinociceptive effect. The antinociceptive dose of URB597 (10 mg/kg) increased plasma and brain anandamide levels. These results suggest that URB597 produces antinociception in these models of 'pain stimulated' and 'pain depressed' behavior, but with different rates of onset and differential involvement of CBRs.
-
Behavioural pharmacology · Apr 2014
Intraganglionar resiniferatoxin prevents orofacial inflammatory and neuropathic hyperalgesia.
Trigeminal ganglion C-fiber neurons bearing transient receptor potential vanilloid-1 (TRPV1) channels are selectively destroyed by resiniferatoxin (RTX), a potent capsaicin analogue. The current study assessed the effect of an RTX injection (200 ng/4 μl) into the trigeminal ganglion in inflammatory and neuropathic rat models of orofacial thermal hyperalgesia. Intraganglionar RTX injection resulted in trigeminal ganglion C-fiber deletion, which was confirmed by the capsaicin eye wipes test, performed 6 days after the injection. ⋯ However, orofacial heat and cold hyperalgesia, induced by carrageenan injected into the upper lip (50 µg/50 μl), was abolished by previous intraganglionar RTX treatment. In addition, the development of orofacial heat and cold hyperalgesia after constriction of the infraorbital nerve was prevented by previous RTX treatment. Thus, trigeminal ganglion neurons expressing TRPV1 are crucial for the development of orofacial inflammatory and neuropathic thermal hyperalgesia.
-
Behavioural pharmacology · Feb 2014
Blockade of CB1 receptors prevents retention of extinction but does not increase low preincubated conditioned fear in the fear incubation procedure.
We recently developed a procedure to study fear incubation, in which rats given 100 tone-shock pairings over 10 days show low fear 2 days after conditioned fear training and high fear after 30 days. Notably, fear 2 days after 10 sessions of fear conditioning is lower than fear seen 2 days after a single session of fear conditioning, suggesting that fear is suppressed. Here, we investigate the potential role of CB1 receptor activation by endocannabinoids in this fear suppression. ⋯ SR141716 injections did not increase fear expression 2 days after extended fear conditioning or affect within-session extinction; however, it impaired retention of between-session fear extinction in the day 3 test. These data suggest that CB1 receptor activation does not suppress fear soon after extended fear conditioning in the fear incubation task. The data also add to the existing literature on the role of CB1 receptors in extinction of conditioned fear.