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BACKGROUND AND PURPOSE Selective cannabinoid CB2 receptor agonists have demonstrated analgesic activity across multiple preclinical pain models. AM1241 is an indole derivative that exhibits high affinity and selectivity for the CB2 binding site and broad spectrum analgesic activity in rodent models, but is not an antagonist of CB2 in vitro functional(More)
Growing evidence supports a role for the immune system in the induction and maintenance of chronic pain. ATP is a key neurotransmitter in this process. Recent studies demonstrate that the glial ATP receptor, P2X7, contributes to the modulation of pathological pain. To further delineate the endogenous mechanisms that are involved in P2X7-related(More)
Intradermal capsaicin injection produces immediate spontaneous pain behaviors, and a secondary mechanical hypersensitivity (SMH) that is employed in the clinic as a model potentially predictive of human neuropathic pain. Presently, we have characterized capsaicin-induced SMH in rats, and compared pharmacological actions of standard analgesics in this and(More)
BACKGROUND AND PURPOSE Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum of preclinical pain models. Selective activation of CB2 receptors may produce analgesia without the undesirable psychotropic side effects associated with modulation of CB1 receptors. To address selectivity in vivo, we describe(More)
BACKGROUND AND PURPOSE To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. EXPERIMENTAL APPROACH We characterized the effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. KEY RESULTS At recombinant(More)
Vanilloid receptor type 1 (TRPV1) is a ligand-gated nonselective cation channel that is considered to be an important integrator of various pain stimuli such as endogenous lipids, capsaicin, heat, and low pH. In addition to expression in primary afferents, TRPV1 is also expressed in the CNS. To test the hypothesis that the CNS plays a differential role in(More)
This study evaluated the effects of systemic indomethacin on carrageenin evoked c-Fos expression in rat lumbar spinal cord neurons. Fos-like immunoreactivity was not observed after the intraplantar injection of the control vehicle saline. 2 h after administration of carrageenin (6 mg/150 microliters) into the hind limb, Fos-like immunoreactive neurons were(More)
The effect of intravenous 7-nitro-indazole (7NI), a selective inhibitor of neuronal nitric oxide synthase, on intraplantar formalin evoked spinal expression of c-Fos was studied. The spinal expression of c-Fos in the superficial laminae of the dorsal horn was not significantly altered by 7NI. In contrast formalin evoked c-Fos expression in the deep laminae(More)
Pre-administered NS-398 (0.1, 1 and 10 mg/kg p.o.), a selective cyclooxygenase-2 inhibitor without gastro-intestinal side-effects, dose-dependently reduced carrageenan evoked spinal c-Fos expression (16 +/- 4%, 32 +/- 3% and 56 +/- 5% reduction, respectively) at 3 h after intraplantar carrageenan. The effects of NS-398 on carrageenan induced peripheral(More)
This study evaluated Fos-like immunoreactivity in lumbar spinal cord neurons following intense cold stimulation and then the modifications induced by opioid administration. Under urethane anaesthesia, the rat's right foot was stimulated by holding it in a regulated temperature bath at 15, 10, 0, -10, -15, -17.5 or -20 degrees C. There was no or little(More)