Newly Published
Pain Medicine  |   January 2020
Supraspinal Opioid Circuits Differentially Modulate Spinal Neuronal Responses in Neuropathic Rats
Author Notes
  • From the Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom (A.H.D., R.P.); Department of Pharmacology, University of Arizona, Tucson, Arizona (E.N., F.P.); and the Department of Pharmacology and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom (K.B.).
  • Part of the work presented in this article has been presented in a poster session at the International Association for the Study of Pain World Pain Congress in Yokohama, Japan, on September 27, 2017.
    Part of the work presented in this article has been presented in a poster session at the International Association for the Study of Pain World Pain Congress in Yokohama, Japan, on September 27, 2017.×
  • Submitted for publication April 14, 2019. Accepted for publication December 3, 2019.
    Submitted for publication April 14, 2019. Accepted for publication December 3, 2019.×
  • Correspondence: Address correspondence to Dr. Bannister: Institute of Psychiatry, Psychology and Neuroscience, Wolfson CARD, Guy’s Campus, King’s College London, London SE1 1UL, United Kingdom. kirsty.bannister@kcl.ac.uk. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Central and Peripheral Nervous Systems / Pain Medicine / Pharmacology / Opioid
Pain Medicine   |   January 2020
Supraspinal Opioid Circuits Differentially Modulate Spinal Neuronal Responses in Neuropathic Rats
Anesthesiology Newly Published on January 21, 2020. doi:https://doi.org/10.1097/ALN.0000000000003120
Anesthesiology Newly Published on January 21, 2020. doi:https://doi.org/10.1097/ALN.0000000000003120
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Descending control from supraspinal neuronal networks onto spinal cord neurons can modulate nociception

  • Endogenous opioids in these brain circuits participate in pain modulation

  • A differential opioidergic role for brain nuclei involved in supraspinal pain modulation has not been previously reported

What This Article Tells Us That Is New:

  • In vivo electrophysiologic recordings from the dorsal horn of the spinal cord in male rats reveal differential effects of morphine at the anterior cingulate cortex, right amygdala, and the ventromedial medulla on evoked pain responses

  • These data differentiate supraspinal opioid circuit regulation of spinal nociceptive processing and suggest that the regulation of sensory and affective components of pain are likely separate

Background: The anterior cingulate cortex and central nucleus of the amygdala connect widely with brainstem nuclei involved in descending modulation, including the rostral ventromedial medulla. Endogenous opioids in these circuits participate in pain modulation. The hypothesis was that a differential opioidergic role for the brain nuclei listed in regulation of spinal neuronal responses because separable effects on pain behaviors in awake animals were previously observed.

Methods: This study utilized in vivo electrophysiology to determine the effects of morphine microinjection into the anterior cingulate cortex, right or left central nucleus of the amygdala, or the rostral ventromedial medulla on spinal wide dynamic range neuronal responses in isoflurane-anesthetized, male Sprague–Dawley rats. Ongoing activity in the ventrobasal thalamus was also measured. In total, 33 spinal nerve ligated and 26 control age- and weight-matched control rats were used.

Results: Brainstem morphine reduced neuronal firing to 60-g von Frey stimulation in control rats (to 65 ± 12% of control response (means ± 95% CI), P < 0.001) with a greater inhibition in neuropathic rats (to 53 ± 17% of control response, P < 0.001). Contrasting anterior cingulate cortex morphine had only marginal modulatory effects on spinal neuronal responses with limited variance in effect between control and neuropathic rats. The inhibitory effects of morphine in the central nucleus of the amygdala were dependent on pain state and laterality; only right-side morphine reduced neuronal firing to 60-g stimulation in neuropathic rats (to 65 ± 14% of control response, P = 0.001). In addition, in neuropathic rats elevated ongoing neuronal activity in the ventral posterolateral thalamus was not inhibited by anterior cingulate cortex morphine, in contrast to evoked responses.

Conclusions: Cumulatively the data support opioid modulation of evoked responses predominately through a lateralized output from the right amygdala, as well as from the brainstem that is enhanced in injured conditions. Minimal modulation of dorsal horn responses was observed after anterior cingulate cortex opioid administration regardless of injury state.