Pain on the brain: NMR tracks analgesics

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  • Published: Apr 1, 2016
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Pain on the brain: NMR tracks analgesics

The image of pain

Nuclear magnetic resonance spectroscopy (NMR) can be used to measure brain metabolites following administration of painkillers and so provide a useful way to evaluate objectively the analgesic effect as well as to study the mode of action of old and new types of painkiller.

Nuclear magnetic resonance spectroscopy (NMR) can be used to measure brain metabolites following administration of painkillers and so provide a useful way to evaluate objectively the analgesic effect as well as to study the mode of action of old and new types of painkiller. Functional magnetic resonance imaging (fMRI) has been used for many years to observe brain activity following the administration of various drugs. However, NMR, or in the clinic, magnetic resonance spectroscopy (MRS) can offer new chemical insights into activity, with a particular focus on metabolic changes.

A clinical investigative study by Tine Maria Hansen, Anne Estrup Olesen, Carsten Wiberg Simonsen, Iben Wendelboe Fischer, Dina Lelic, Asbjørn Mohr Drewes and Jens Brøndum Frøkjær of the Department of Radiology, at Aalborg University Hospital, in Denmark, suggests a novel approach to monitoring and tracking the effects of different types of analgesics. The team points out that their exploratory work could fill a gap in analgesic research where there are only limited data available in the spectroscopy domain of metabolites. Critically, it could help in pain relief as people respond differently to different analgesics in terms of benefits or lack thereof and in terms of side effects. As such, the team investigated the central effects of two common analgesic drugs, an opioid and a selective serotonin and norepinephrine reuptake inhibitor. This allowed the team to explore whether or not there is a connection between changes in metabolites in the brain and the degree of analgesic effect and any side effects.

Ratio rations

The team carried out single voxel proton NMR spectroscopy in the anterior cingulate cortex, insula and prefrontal cortex of twenty healthy subjects before and after treatment for five days with oxycodone (eight doses of 10 milligrams as an extended release formulation), venlafaxine (eight doses of 37.5 mg also extended release). One group were given a placebo in the standard randomized double-blind control fashion. The spectral data were used to monitor the metabolites of glutamate, N-acetylaspartate, and myo-inositol as a ratio to creatine, the team explain in the March issue of the Journal of Neuroimaging.

Pain relief

The team found that in all the regions of the brain monitored, the ratio of glutamate to creatine ratio fell by 8.4% ± 0.3% after treatment with oxycodone and by 6.6% ± 0.4% after administering venlafaxine, both changes being relative to the placebo control group. Indeed, there was not a statistically significant difference across any brain region. However, administering the painkillers had no effect on the ratio of N-acetylaspartate to creatine nor on myo-inositol to creatine. The team did not, however, find an association between the treatment-induced change in glutamate to creatine ratio and the analgesic effect of the drug nor of any side effects.

Understanding the biochemistry in the brain associated with pain perception and the effect of analgesic drugs is critical to the future development of novel approaches to pain relief that might avoid deleterious side effects, tolerance and addiction problems, associated with so many current painkillers and in particular the opioids.

"The next step is to apply the experimental imaging model on diseases with chronic pain," Frøkjær told SpectroscopyNOW. "We are right now doing a study in patients with painful chronic pancreatitis, with 1) comparison to healthy subjects, and 2) assessing the effect of pain treatment with ketamin. We do MR-spectroscopy, structural scans for volumetry and cortical thickness assessment, and resting-state fMRI looking into the functional connectivity. Hence, with a full MRI model we aim to assess the pain system with structural, functional and metabolic information." He adds that, "The hypothesis is that we somehow can improve/reset the pain system, the neuropathic pain mechanisms, and the neuroplastic changes."

Related Links

J Neuroimaging 2016, online: "Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy Study"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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