2011). ERK1/2 phosphorylation constitutes a selective cell HKI-272 in vitro marker which occurs in response to noxious stimulus (Ji et al. 1999) and not to nonnoxious stimulus such as light touch. This study first aimed at determining whether nigrostriatal

dopamine depletion could induce trigeminal DMA in the rat. We used an animal model for PD (Paillé et al. 2007; Zengin-Toktas et al. 2013). In this model, lesions within the substantia nigra compacta (SNc) and ventral tegmental area (VTA) were obtained by injecting the 6-OHDA into the medial forebrain bundle. Second, Inhibitors,research,lifescience,medical we asked whether a local segmental mechanism is implicated in this type of allodynia. Finally, we investigated whether the action of bromocriptine, a dopamine 2 receptor (D2R) agonist drug, has analgesic effects in this animal model of PD. Inhibitors,research,lifescience,medical Materials and Methods Ethical statement The experiments conformed to the ethical guidelines of the International Association for the Study of Pain, the European Community Council directive of 24 November 1986 (86/609/EEC) and the Animal Ethics Committee of the University of Auvergne (CE08-11). All surgery was performed under anesthesia, and every effort

was made to minimize animal suffering Inhibitors,research,lifescience,medical and number. The rats were kept in specified pathogen-free conditions, and all the procedures performed were approved by the Auvergne University ethics committee. Surgery Eighty-two adult male Sprague–Dawley rats (275–325 g) from Charles River (L’Arbresle, France) were obtained and maintained in a controlled

environment (lights on 07:00–19:00, 22°C) with Inhibitors,research,lifescience,medical ad libitum access to food and water. They were housed three to four per cage. The experiment was performed as described previously (Paillé et al. 2007; Zengin-Toktas et al. 2013). Anesthesia was given with ketamine 60 mg/kg, i.p. and Rompun® (Bayer, France) (xylazine, 10 mg/kg, i.p.). The animals were placed in a stereotaxic frame Inhibitors,research,lifescience,medical (David Kopf Instrument, Tujunga, CA). Eighty-two rats were injected bilaterally in the substantia nigra compacta (SNc) with 6-OHDA (6-hydroxy dopamine, 0.5 μL/min) after dissolution in a vehicle solution (0.02% ascorbate saline) at a concentration of 3 μg/μL Rolziracetam (Sigma-Aldrich, Saint-Quentin, France) in two deposits (2.25 and 2.85 μg, respectively) at the following coordinates (in mm relative to bregma and the surface of the dura mater): posterior (P) −4.0; lateral (L) ± 0.8; ventral (V) −8.0; tooth bar at +3.4 and A −4.4; L ± 1.2; V −7.8; tooth bar at −2.4. In order to preserve adrenergic neurons from 6-OHDA toxicity, the animals received desipramine (25 mg/kg, i.p., Sigma-Aldrich) 30 min prior to the toxin injection; sham-lesioned rats received only the vehicle at the same coordinates. Drugs The following drugs were used: bromocriptine (Sigma-Aldrich) dissolved in 0.9% saline, and sulpiride (Sigma-Aldrich) dissolved in 2.5% HCL, 7.5% dimethyl sulfoxide (DMSO), 90% saline (0.9%). Fresh solutions were prepared just prior to use. In line with our previous study (Zengin-Toktas et al.