Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

Neuron. 2021 Jan 6;109(1):73-90.e7. doi: 10.1016/j.neuron.2020.10.027. Epub 2020 Nov 11.


The spinal dorsal horn is a major site for the induction and maintenance of mechanical allodynia, but the circuitry that underlies this clinically important form of pain remains unclear. The studies presented here provide strong evidence that the neural circuits conveying mechanical allodynia in the dorsal horn differ by the nature of the injury. Calretinin (CR) neurons in lamina II inner convey mechanical allodynia induced by inflammatory injuries, while protein kinase C gamma (PKCγ) neurons at the lamina II/III border convey mechanical allodynia induced by neuropathic injuries. Cholecystokinin (CCK) neurons located deeper within the dorsal horn (laminae III-IV) are important for both types of injuries. Interestingly, the Maf+ subset of CCK neurons is composed of transient vesicular glutamate transporter 3 (tVGLUT3) neurons, which convey primarily dynamic allodynia. Identification of an etiology-based circuitry for mechanical allodynia in the dorsal horn has important implications for the mechanistic and clinical understanding of this condition.

Keywords: calretinin; cholecystokinin; dorsal horn; inflammatory pain; mechanical allodynia; neural circuitry; neuropathic pain; pain; protein kinase C gamma; vesicular glutamate transporter 3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Acidic / metabolism
  • Animals
  • Female
  • Hyperalgesia / metabolism*
  • Hyperalgesia / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / chemistry
  • Nerve Net / metabolism*
  • Nerve Net / pathology
  • Pain Measurement / methods*
  • Spinal Cord Dorsal Horn / chemistry
  • Spinal Cord Dorsal Horn / metabolism*
  • Spinal Cord Dorsal Horn / pathology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology


  • Amino Acid Transport Systems, Acidic
  • vesicular glutamate transporter 3, mouse