Pain mechanismPeriaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5 receptors modulate changes in rostral ventromedial medulla neuronal activities induced by subcutaneous formalin in the rat
Section snippets
Animals and surgical preparation
Male Wistar rats (250–300 g) were housed three per cage under controlled illumination (12-h light/dark cycle; light on 06:00 h) and standard environmental conditions (ambient temperature 20–22 °C, humidity 55–60%) for at least 1 week before the commencement of experiments. Rat chow and tap water were available ad libitum. All surgery and experimental procedures were done during the light cycle and were approved by the Animal Ethics Committee of the Second University of Naples (Napoli, Italy).
Results
The results are based on a total of 236 RVM neurons at a depth of 8875–10,730 μm, the estimated location of the neurons being in nucleus raphe magnus, nucleus reticularis gigantocellularis pars α, and nucleus reticularis paragigantocellularis (Fig. 1). All recorded neurons were spontaneously active and discharged with a mean frequency of 7.6±0.7 (ON-cells) and 8.3±0.8 (OFF-cells) spikes/s. These neurons were identified by the characteristic OFF-cell pause, and ON-cell burst, of activity just
Discussion
Dorsal-lateral PAG was considered in this study because previous data from this laboratory showed that PAG glutamate receptors were required for cannabinoid-mediated antinociception, and that glutamate and cannabinoid systems may functionally interact at that level for the modulation of acute sensory thermoceptive stimuli (Palazzo et al., 2001).
The findings from the current study suggest that the cannabinoid agonist WIN 55,212-2 given into the dorsal-lateral PAG was effective in decreasing or
Acknowledgments
This study was supported by MIUR (PRIN 2003), Italy. We thank Professor Vincenzo Di Marzo (Endocannabinoid Research Group, CNR, Naples, Italy) for stimulating discussion and comments on the manuscript. We also thank Sanofi-Synthelabo Recherche (Montpellier, France) very much for the gift of SR141716A.
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2016, Advances in PharmacologyCitation Excerpt :Interestingly, within the periaqueductal gray matter (PAG), activation of all groups of mGluRs, including group I mediate antinociceptive effects presumably by the activation of the descending antinociceptive pathways via the inhibition of the GABAergic transmission (Drew & Vaughan, 2004; Maione et al., 2000). In addition, in the PAG, mGluR5 seems to participate in the analgesic effects mediated by cannabinoids (de Novellis et al., 2005; Palazzo et al., 2001). Group I mGluRs are also highly expressed in the prefrontal cortex, a region involved in decision-making functions and behavioral control which has been shown to be impaired in patients suffering from chronic pain (Apkarian et al., 2004) and in animal models of inflammatory and neuropathic pain (Ji et al., 2010; Metz, Yau, Centeno, Apkarian, & Martina, 2009; Pais-Vieira, Mendes-Pinto, Lima, & Galhardo, 2009).