GABAA-Receptor Blockade Reverses the Injury-Induced Sensitization of Nociceptor-Specific (NS) Neurons in the Spinal Dorsal Horn of the Rat

Abstract

Single-unit electrical activity was recorded from 80 nociceptor-specific (NS) neurons in the dorsal horn of the lumbar spinal cord of pentobarbital anesthetized rats. Their responses to low- and high-intensity mechanical stimulation of their receptive fields (RFs) were recorded before and after the application of irritant agents [capsaicin (CAP) or mustard oil (MO)] to the RF. Before the applications of the irritants the neurons responded only to high-intensity stimuli, but after this procedure 20 of 28 neurons tested were sensitized, i.e., gave increased responses to high-intensity stimuli and showed novel responses to low-intensity mechanical stimulation as well as an Aβ-fiber afferent drive. CAP was more likely to induce sensitization than MO and the majority of sensitized neurons were located in the superficial dorsal horn. No relationship was found between the magnitude of the response to the sensitizing agent and the presence or absence of sensitization. Cumulative doses of two γ-aminobutyric acid type A (GABA_A)–receptor antagonists, picrotoxin and bicuculline, were administered systemically or applied directly over the spinal cord. The GABA_A antagonists reversed the sensitization of the neurons by reducing the novel low-threshold responses. These results show that NS neurons in the spinal dorsal horn can be sensitized by a sustained afferent discharge in peripheral nociceptors and that this sensitization can be reduced or reversed by low doses of GABA_A-receptor antagonists. This provides evidence for a mechanism in which an enhanced GABAergic transmission can lead to hyperexcitability and sensitization of NS neurons in the dorsal horn.