Aim of Investigation: Sensory neurons of the dorsal root ganglia (DRG) are heterogeneous in order to respond to a variety of environmental stimuli (e.g. noxious heat or light touch) and transmit somatosensory information to spinal neurons. Opioids relieve pain in part by acting on DRG neurons, but the precise identity of the cells in which activity is regulated by opioids remains unclear. Here we determined the molecular identity of DRG neurons that express opioid receptors and tested the hypothesis that the delta opioid receptor (DOR) controls Abeta low-threshold mechanoreceptor inputs to spinal cord neurons.Methods: We used a combination of mouse genetics, neuroanatomical and electrophysiological approaches. We first used knockin mice expressing a DOReGFP receptor and a panoply of markers for distinct populations of DRG neurons to localize DOR in DRG and skin by immunohistochemistry. We next performed whole cell patch clamp recording in spinal cord slices to investigate the effect of opioid agonists on synaptic transmission between DRG and spinal dorsal horn neurons.Results: We found that DOR is expressed by several populations of mechanonociceptors, as well as by Ret and TrkC coexpressing Abeta low-threshold mechanoreceptors that innervate touch-sensing organs in the skin. By contrast, the mu opioid receptor (MOR) is predominantly expressed by thermonociceptors, as well as by a small population of putative AM mechanonociceptors in which MOR and DOR are colocalized at the plasma membrane. In spinal cord slices from wild-type mice, we found that the DOR agonist deltorphin depresses Abeta synaptic input to laminae III-V spinal neurons, consistent with our anatomical findings.Conclusions: Collectively our results indicate that the function of the opioid system in somatosensation is not restricted to the regulation of nociceptive inputs to the spinal cord but also includes control of touch information, thereby providing a rationale for targeting DOR in clinical situations where pain results from a dysfunction of Abeta low-threshold mechanoreceptors.
CONTROL OF Abeta LOW-THRESHOLD MECHANORECEPTOR INPUTS TO SPINAL CORD NEURONS BY DELTA OPIOID RECEPTORS / G., Scherrer; Bardoni, Rita; P., Choudhury; B. L., Kieffer; A., Basbaum; A. B., Macdermott. - ELETTRONICO. - 1:(2012), pp. PW 266-PW 266. (Intervento presentato al convegno 14th world pain meeting tenutosi a Milano nel 27-31/8/2012).