Dorsal Horn Circuits for Persistent Mechanical Pain

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-08, Vol.87 (4), p.797-812
• Main Authors: Peirs, Cedric, Williams, Sean-Paul G., Zhao, Xinyi, Walsh, Claire E., Gedeon, Jeremy Y., Cagle, Natalie E., Goldring, Adam C., Hioki, Hiroyuki, Liu, Zheng, Marell, Paulina S., Seal, Rebecca P.
• Format: Article
• Language: English
• Subjects: Amino Acid Transport Systems, Acidic - biosynthesis; Animals; Behavior; Colleges & universities; Control theory; Defects; Hyperalgesia - metabolism; Hyperalgesia - pathology; Life Sciences; Mice; Mice, Knockout; Morphology; Nerve Net - metabolism; Nerve Net - pathology; Neurobiology; Neurons; Neurons and Cognition; Organ Culture Techniques; Pain; Pain - metabolism; Pain - pathology; Rodents; Spinal cord; Spinal Cord Dorsal Horn - metabolism; Spinal Cord Dorsal Horn - pathology; Touch
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2015.07.029

Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain. [Display omitted] •Deep dorsal horn neurons transiently express VGLUT3 and convey mechanical allodynia•They receive innocuous input and reside at the interface between touch and pain•Their local activation reveals a dorsally directed pathway for mechanical allodynia•Different microcircuits encode mechanical allodynia depending on the injury Peirs et al. identified deep dorsal horn neurons that transiently express VGLUT3 and are required for mechanical allodynia. The neurons transmit innocuous input to dorsally directed pain microcircuits that are differentially engaged depending on the type of injury.