Rat Dorsal Horn Nociceptive-Specific Neurons Are More Sensitive Than Wide Dynamic Range Neurons to Depression by Immobilizing Doses of Volatile Anesthetics: An Effect Partially Reversed by the Opioid Receptor Antagonist Naloxone

Abstract

Background The mechanism and site of action within the spinal cord by which volatile anesthetics produce immobility are not well understood. Little work has been done directly comparing anesthetic effects on neurons with specific functional characteristics that mediate transfer of nociceptive information within the spinal cord. Materials and Methods Adult male rats were anesthetized and prepared for extracellular single-unit recordings from the lumbar dorsal horn. Nociceptive-specific (NS) and wide dynamic range (WDR) neurons were identified and noxious-heat evoked neuronal spike rates evaluated at 0.8 and 1.2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane. In another group, noxious-heat evoked responses from NS neurons were evaluated at 0.8, 1.2 MAC halothane, and 1.2 MAC halothane plus IV naloxone (0.1 mg/kg). Results Increasing halothane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal responses of NS neurons (n=9) from 827 ± 122 (mean ± SE) to 343 ± 48 spikes/ min (p < 0.05) but not WDR neurons (n=9), 617 ± 79 to 547 ± 78 spikes/min. Increasing isoflurane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal response of NS neurons (n=9) from 890 ± 339 to 188 ± 97 spikes/ min (p < 0.05), but did not alter the response of WDR neurons (n=9) in which evoked spike rate went from 576 ± 132 to 601 ± 119 spikes/min. In a separate group, the response from NS neurons went from 282 ± 60 to 74 ± 32 spikes/min (p < 0.05) when halothane was increased from 0.8 to 1.2 MAC. Intravenous administration naloxone increased the heat-evoked response to 155 ± 46 spikes/min (p < 0.05). Conclusions NS but not WDR neurons in the lumbar dorsal horn are depressed by peri-MAC increases of halothane and isoflurane. This depression, at least with halothane, can be partially reversed by the opioid antagonist naloxone. Given that opioid receptors are not likely involved in the mechanisms by which volatile anesthetics produce immobility, this suggests that, although the neuronal depression is of substantial magnitude and occurs concurrent to the production of immobility, it may not play a major role in the production of this anesthetic end-point.

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

“…Nociceptive afferent inputs are mostly mediated by C‐fibers that terminate in the superficial dorsal horn . Future electrophysiology studies are needed to determine how different patterns of subthreshold SCS modulate in vivo spinal nociceptive transmission under neuropathic pain condition, such as by measuring spinal local field potentials that correspond to C‐fiber inputs and by examining responses of wide‐dynamic range neurons and nociceptive‐specific neurons in the dorsal horn .…”

Comparison of Spinal Anesthetic Effect between Emulsified Isoflurane and Emulsified Nonimmobilizer F6

“…Besides voltage-gated sodium channel, many other neuronal transmitters receptors might also be involved in spinal effects of volatile anesthetics, such as γ-aminobutyric acid (28), N-methyl-D -aspartic acid (29)(30)(31), opium (32), and acetylcholine and adrenergic (33) receptors. Thus, spinal effect of isoflurane might be a comprehensive outcome resulting from its modulations on multiple targets.…”

Inhibition of Voltage-Gated Sodium Channels by Emulsified Isoflurane May Contribute to Its Subarachnoid Anesthetic Effect in Beagle Dogs

“…Besides voltage-gated Na + channel, accumulating evidence suggests that many receptors and neuronal transmitters are involved in spinal action of volatile anesthetics, including F-aminobutyric acid, 17 N-methyl-D-aspartic acid, 18Y20 opium, 21 and acetylcholine and adrenergic receptors. 22 Thus, it is possible that other receptors and neuronal transmitters also contribute to the spinal effect of isoflurane.…”