Dorsal horn circuitry Complexity and implications for mechanisms of neuropathic pain

The transmission of pain involves several types of primary unmyelinated A- and unmyelinated C afferents from neurons in in the dorsal root (or trigeminal) ganglion; these afferents activate second-order spinothalamic and spinobulbar projection neurons in the dorsal horn (or trigeminal nucleus caudalis). The dorsal horn is not a simple relay station but rather a site of complex processing and gating of nociceptive information via circuits involving different subtypes of excitatory or inhibitory interneurons. These neurons are the target of descending pain-modulatory influences from the rostral ventromedial medulla and other regions. Pain circuits also participate in the relay and processing of the sensation of itch. Specific molecular markers, such as transient receptor potential (TRP) channels and Mas-related G-protein-coupled receptor (Mrgpr) subtypes, have allowed the identification of different subtypes of primary afferents transmitting pain and itch sensations. The application of transgenic and ablation techniques has provided insight into the heterogeneity of excitatory or inhibitory interneurons and their involvement in dorsal horn circuits regulating transmission and gating of pain and itch. Excitatory interneurons have a major role in both normal and abnormal transmission of sensory input to the projection neurons; inhibitory interneurons are critically involved in gating these inputs. These findings provide new insights into the pathophysiology of the manifestations of neuropathic pain, including spontaneous pain, hyperalgesia, and mechanical allodynia, as well as neuropathic itch. There are several reviews on all these topics.(1-19) This review is focused on the spinal dorsal horn, although similar processes likely underlie facial trigeminal-mediated pain.