Itch mechanisms and circuits

Abstract

The itch-scratch reflex serves as a protective mechanism in everyday life. However, chronic persistent itching can be devastating. Despite the clinical importance of the itch sensation, its mechanism remains elusive. In the past decade, substantial progress has been made to uncover the mystery of itching. Here, we review the molecules, cells, and circuits known to mediate the itch sensation, which, coupled with advances in understanding the pathophysiology of chronic itching conditions, will hopefully contribute to the development of new anti-itch therapies.

Keywords: itch; neural circuits; neurons; pain; pruritus; sensitization.

Figure 1

Schematic drawing of the neuronal interactions between dorsal root ganglia (DRG) neurons and spinal neurons in the itch and pain pathways. The neural pathways for pain (red) and for itch (blue) are shown. The bold lines indicate the activated pathways. (a) When pruriceptive DRG neurons are selectively activated by either pruriceptive or nociceptive (e.g., capsaicin) stimuli, the itch sensation is produced (labeled-line theory) (44). (b) When nociceptive stimuli activate both pruriceptive and nociceptive DRG neurons, the itch sensation is suppressed by the inhibitory spinal interneurons, and only the pain sensation is produced (population theory) (71, 84, 101). For the purposes of this illustration, the sensory fibers of all DRG neurons are bundled into one single line to represent the peripheral and central terminals. Each different population of spinal neurons is represented by a single neuron. Minus signs indicate the inhibitory synapse between the interneuron and the pruriceptive spinal neuron. Figure modified with permission from Reference .