The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation

Aubrey P Yao, JongBun Kim, Richard Atherley, Steven L. Jinks, Earl Carstens, Sean Shargh, Alana Sulger, Joseph F. Antognini

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors. METHODS: Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0-1.2 MAC. RESULTS: In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60%, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25%), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response. CONCLUSIONS: The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on γ-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.

Original languageEnglish (US)
Pages (from-to)1759-1764
Number of pages6
JournalAnesthesia and Analgesia
Volume106
Issue number6
DOIs
StatePublished - Jun 2008

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Anesthetics
Posterior Horn Cells
Benzene
Spinal Cord
Aminobutyrates
Spinal Cord Dorsal Horn
Nociceptors
GABA Receptors
Laminectomy
Nociception
Aspartic Acid
hexafluorobenzene
Neurons
aspartic acid receptor

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Yao, A. P., Kim, J., Atherley, R., Jinks, S. L., Carstens, E., Shargh, S., ... Antognini, J. F. (2008). The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation. Anesthesia and Analgesia, 106(6), 1759-1764. https://doi.org/10.1213/ane.0b013e3181732ee3

The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation. / Yao, Aubrey P; Kim, JongBun; Atherley, Richard; Jinks, Steven L.; Carstens, Earl; Shargh, Sean; Sulger, Alana; Antognini, Joseph F.

In: Anesthesia and Analgesia, Vol. 106, No. 6, 06.2008, p. 1759-1764.

Research output: Contribution to journalArticle

Yao, AP, Kim, J, Atherley, R, Jinks, SL, Carstens, E, Shargh, S, Sulger, A & Antognini, JF 2008, 'The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation', Anesthesia and Analgesia, vol. 106, no. 6, pp. 1759-1764. https://doi.org/10.1213/ane.0b013e3181732ee3
Yao, Aubrey P ; Kim, JongBun ; Atherley, Richard ; Jinks, Steven L. ; Carstens, Earl ; Shargh, Sean ; Sulger, Alana ; Antognini, Joseph F. / The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation. In: Anesthesia and Analgesia. 2008 ; Vol. 106, No. 6. pp. 1759-1764.
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abstract = "BACKGROUND: Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors. METHODS: Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0-1.2 MAC. RESULTS: In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60{\%}, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25{\%}), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response. CONCLUSIONS: The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on γ-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.",
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AU - Yao, Aubrey P

AU - Kim, JongBun

AU - Atherley, Richard

AU - Jinks, Steven L.

AU - Carstens, Earl

AU - Shargh, Sean

AU - Sulger, Alana

AU - Antognini, Joseph F.

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N2 - BACKGROUND: Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors. METHODS: Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0-1.2 MAC. RESULTS: In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60%, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25%), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response. CONCLUSIONS: The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on γ-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.

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