Spinal μ and δ opioids inhibit both thermal and mechanical pain in rats

The expression and contribution of micro (MOPR) and δ opioid receptors (DOPR) in polymodal nociceptors have been recently challenged. Indeed, MOPR and DOPR were shown to be expressed in distinct subpopulation of nociceptors where they inhibit pain induced by noxious heat and mechanical stimuli, respectively. In the present study, we used electrophysiological measurements to assess the effect of spinal MOPR and DOPR activation on heat-induced and mechanically induced diffuse noxious inhibitory controls (DNICs). We recorded from wide dynamic range neurons in the spinal trigeminal nucleus of anesthetized rats. Trains of 105 electrical shocks were delivered to the excitatory cutaneous receptive field. DNICs were triggered either by immersion of the hindpaw in 49°C water or application of 300 g of mechanical pressure. To study the involvement of peptidergic primary afferents in the activation of DNIC by noxious heat and mechanical stimulations, substance P release was measured in the spinal cord by visualizing neurokinin type 1 receptor internalization. We found that the activation of spinal MOPR and DOPR similarly attenuates the DNIC and neurokinin type 1 receptor internalization induced either by heat or mechanical stimuli. Our results therefore reveal that the activation of spinal MOPR and DOPR relieves both heat-induced and mechanically induced pain with similar potency and suggest that these receptors are expressed on polymodal, substance P-expressing neurons.