Abstract
Metabotropic glutamate receptor 5 (mGluR5) activation in the infralimbic cortex (IL) induces pronociceptive behavior in healthy and monoarthritic rats. Here we studied whether the medullary dorsal reticular nucleus (DRt) and the spinal TRPV1 are mediating the IL/mGluR5-induced spinal pronociception and whether the facilitation of pain behavior is correlated with changes in spinal dorsal horn neuron activity. For drug administrations, all animals had a cannula in the IL as well as a cannula in the DRt or an intrathecal catheter. Heat-evoked paw withdrawal was used to assess pain behavior in awake animals. Spontaneous and heat-evoked discharge rates of single DRt neurons or spinal dorsal horn wide-dynamic range (WDR) and nociceptive-specific (NS) neurons were evaluated in lightly anesthetized animals. Activation of the IL/mGluR5 facilitated nociceptive behavior in both healthy and monoarthritic animals, and this effect was blocked by lidocaine or GABA receptor agonists in the DRt. IL/mGluR5 activation increased spontaneous and heat-evoked DRt discharge rates in healthy but not monoarthritic rats. In the spinal dorsal horn, IL/mGluR5 activation increased spontaneous activity of WDR neurons in healthy animals only, whereas heat-evoked responses of WDR and NS neurons were increased in both experimental groups. Intrathecally administered TRPV1 antagonist prevented the IL/mGluR5-induced pronociception in both healthy and monoarthritic rats. The results suggest that the DRt is involved in relaying the IL/mGluR5-induced spinal pronociception in healthy control but not monoarthritic animals. Spinally, the IL/mGluR5-induced behavioral heat hyperalgesia is mediated by TRPV1 and associated with facilitated heat-evoked responses of WDR and NS neurons.