Spinal Circuits Transmitting Mechanical Pain and Itch

Abstract

In 1905, Henry Head first suggested that transmission of pain-related protopathic information can be negatively modulated by inputs from afferents sensing innocuous touch and temperature. In 1965, Melzak and Wall proposed a more concrete gate control theory of pain that highlights the interaction between unmyelinated C fibers and myelinated A fibers in pain transmission. Here we review the current understanding of the spinal microcircuits transmitting and gating mechanical pain or itch. We also discuss how disruption of the gate control could cause pain or itch evoked by innocuous mechanical stimuli, a hallmark symptom for many chronic pain or itch patients.

Keywords: Gate control; Itch; Pain; Spinal cord.

Fig. 1

Laminar organization of the spinal dorsal horn. A Laminar organization of dorsal horn and primary afferent inputs, modified from Craig [19]. B The gate control theory proposed in 1965. T, transmission neurons; IN, inhibitory neurons in the substantia gelatinosa (lamina II) of the dorsal horn.

Fig. 2

Transmission of mechanical versus heat pain. A Three types of projection neuron located in lamina I and deep laminae, including mechanical-selective (yellow), heat-selective (red), and polymodal (green) projection neurons. B, C SOM lineage neurons (marked after crossing SOM^Cre with tdTomato reporter mice, as previously described [34]), are enriched in laminae II and III, ventral to NK1R⁺ projection neurons in lamina I (B). Biocytin labeling showing a SOM^tdTomato neuron in lamina II that is a vertical cell (C). Image in C adapted from Duan et al. [34].

Fig. 3

Schematic showing the spinal circuits that transmit mechanical pain-related information. CR^+/−, transient-central cells partly marked by Calb2/calretinin^Cre (CR^+/−); SOM^+/− cell (blue), vertical neuron in lamina II_o; P, projection neuron in lamina I; IN, inhibitory interneuron at the II-III border or within lamina III, including the Dyn, PV, GlyT2, and Ret lineage neurons. Modified from Duan et al. [34].

Fig. 4

Schematic showing the gate control of mechanical itch. LTMR, low-threshold mechanoreceptor; T, a mechanical itch transmission neuron, which could be a projection neuron or an excitatory interneuron.