Nociceptive spinal withdrawal reflexes but not spinal dorsal horn wide‐dynamic range neuron activities are specifically inhibited by halothane anaesthesia in spinalized rats

Abstract

The aim of the present study was to investigate the spinal cord effects and sites of action of different inhaled concentrations (0.5-2%) of the anaesthetic, halothane. Simultaneous recordings were made of 3 Hz, suprathreshold (1.5 x T) electrically evoked spinal dorsal horn (DH) wide-dynamic range (WDR) neuron responses and of single motor unit (SMU) electromyographic (EMG) responses underlying the spinal withdrawal reflex in spinalized Wistar rats. Compared with the baseline responses obtained with 0.5% halothane, the electrically evoked early responses of the DH WDR neurons as well as the SMUs were only depressed by the highest, 2% concentration of halothane. In contrast, 1.5% halothane markedly inhibited the late responses of the DH WDR neurons, whereas 1% halothane started to significantly depress the late responses of the SMUs. Likewise, wind-up of the WDR neuron late responses was inhibited by 1.5-2% halothane, whereas 1-2% halothane significantly depressed wind-up of the SMU EMG late responses. The inhibitory effects of 2% halothane on the early and the late responses of the DH WDR neurons, but not of the SMUs, were completely reversed by opioid micro-receptor antagonist naloxone (0.04 mg/kg). However, no significant effects of naloxone were found on different responses of the DH WDR neurons as well as the SMUs at 0.5-1% halothane, suggesting that different concentrations of halothane may modulate different spinal receptors. We conclude that halothane at high concentrations (1.5-2%) seems to play a predominant inhibitory role via spinal multireceptors on ventral horn (VH) motor neurons, and less on DH sensory WDR neurons, of the spinal cord.

Transient tactile allodynia following intrathecal puncture in mouse: Contributions of Toll-like receptor signaling

“…Given those circumstances, allodynia is not surprising as the acute activation of high-threshold sensory afferents will initiate spinal facilitatory processes, which likely account for the observed tactile allodynia [16]. Though the animal is anesthetized, afferent-evoked spinal sensitization has been routinely demonstrated in animals anesthetized with volatile anesthetics [4, 28]. Previous work, with intentional needle sticks of the peripheral nerve, has shown the development of evident and persistent tactile allodynia in animals [17, 26].…”

Validation and Insights of Anesthetic Action in an Early Vertebrate Network

“…This result implicates “ventral horn” locomotor circuits as the primary spinal site for anesthetic-induced immobility in lampreys. In rats, ventral horn neurons are substantially more sensitive to volatile anesthetics and propofol compared to dorsal horn neurons (7-9). Therefore both vertebrate orders exhibit similar differences in anesthetic sensitivity between sensory and motor components of nociceptive sensorimotor circuits.…”

“…Although the degree of supraspinal effects varies across anesthetic classes (2-4), the spinal cord is considered the primary locus for anesthetic-induced immobility (5,6). Spinal immobilizing effects appear to be mediated primarily within the ventral horn (7-9), where there reside motor neurons and locomotion-generating interneuronal networks, termed the central pattern generator (CPG). In isolation, spinal locomotor networks of both lamprey and mammals produce coordinated rhythmic motor output (10,11), which is typically assessed in MAC determination (12).…”

Brainstem Regions Affecting Minimum Alveolar Concentration and Movement Pattern during Isoflurane Anesthesia

“…Our current focus on the MLR was warranted by previous studies demonstrating that volatile anesthetics produce immobility mainly by affecting ventral spinal circuitry,8 possibly locomotor networks,6,28 and not by an action on sensory dorsal horn neurons 9,27,29–31. Thus, the main brainstem influence on MAC in intact animals must be derived from effects on descending motor commands, more so than from descending nociceptive modulation.…”