Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons

Abstract

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.

Figure 1

STT neurons are reliably activated by scratching, often with an after-discharge. (a) A histamine-sensitive STT neuron scratched before the histamine application (inset, receptive field and direction of scratching). (b) A histamine-insensitive STT neuron scratched before the histamine application. The time of each action potential is represented by a vertical line located below the histogram. All experiments were approved by the Institutional Animal Care and Use Committee of the University of Minnesota.

Figure 2

Scratching inhibits histamine-evoked activation of STT neurons. (a) Discharge rates of an STT neuron activated by histamine before, during and following repeated scratching (black horizontal bars) of the cutaneous receptive field. The time scale is magnified below. (b,c) Recording site (arrow, b) and receptive field (c) of the neuron shown in a. H, histamine injection site. (d) Another histamine-sensitive STT neuron that was inhibited by repeated scratching. (e) Firing rates 10 s before and after (dotted lines) scratching in histamine-responsive STT neurons before the histamine application were not different (mean ± s.e.m., n = 8, Wilcoxon signed rank test, P = 0.2). (f) The time course before and after scratching of the firing rate during a response to histamine (mean ± s.e.m.). (g) Mean discharge rate of each histamine-responsive STT neuron during the 10 s before and the 10 s immediately after scratching during the response to histamine. Arrowhead indicates the high-threshold STT neuron. Open circles represent the group mean ± s.e.m., which was significantly reduced after scratching (n = 8, Wilcoxon signed rank test, P = 0.008).

Figure 3

State-dependency of inhibition. (a) The neuron shown in Figure 2d was not inhibited following scratching during a response to capsaicin. (b) Discharge rate (mean ± s.e.m.) during the response to capsaicin was not inhibited after scratch in histamine-responsive neurons (n = 4, Wilcoxon signed rank test, P = 0.25) and was increased for all STT neurons scratched during capsaicin treatment (n = 11, Wilcoxon signed rank test, P = 0.02). (c) Post-scratch activity given as a percentage of the pre-scratch activity (mean ± s.e.m. were measured). Only histamine-sensitive neurons scratched during the histamine response were inhibited (Kruskal-Wallis ANOVA and Dunn’s post-test, P = 0.009).