Objective methods for the assessment of the spinal and supraspinal effects of opioids
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Satu K. Jääskeläinen
In this issue of the Scandinavian Journal of Pain, Fischer and coworkers [1] review several methods available for objective measurement of the central nervous system (CNS) effects of opioids and opioid induced analgesia, both at the spinal and the supraspinal levels. This is an important issue as objective, quantifiable markers for opioid analgesia would be of utmost importance both in basic research and drug development, as well as in the assessment of therapeutic efficacy and drug resistant pain conditions in the clinic. Nevertheless, clinical trials mostly rely on subjective reports on the pain estimated with visual analogue scale (VAS) or numerical rating scale (NRS). The task to reduce the subjective, multidimensional experience of pain to objective biomarkers is challenging. This review [1] ambitiously tackles the problem showing many potential tools already available for the assessment of central nervous system effects of opioids and their relationship to analgesia but, simultaneously, it highlights the problems and open questions in the field.
1 The methods available for objective assessment of opioid effects
Pupillometry seems to be a reliable and feasible measure to assess central opioid effects even on the chair-side as the authors have previously shown [2]. However, as the pupillary size is controlled by many external (e.g. ambience light) and internal factors (e.g. anxiety) via the autonomous system that can also be affected by peripheral neuropathy or central nervous system lesions, its clinical use may be complicated. In addition, usefulness of pupillometry in patients on chronic opioid therapy should be evaluated in future clinical studies as most of the current data comes from experimental studies on acute opioid administration in healthy subjects or recreational opioid users [1].
2 More direct assessment of the CNS effects of opioids
Functional brain imaging with pharmaco-fMRI or neurotransmitter PET scans offer reliable precision-tools, but require expensive equipment, qualified personnel, and time. Thus, they may be more suitable for scientific studies than for clinical work.
3 Neurophysiological methods
Nociceptive flexion reflex (RIII), electroencephalography (EEG), and somatosensory (SEP) or pain evoked potentials (LEP, CHEP) might provide less expensive and more feasible means to analyze opioid effects. They also allow dissecting the spinal and supraspinal components, and simultaneously control the non-specific sedative effects of opioids. However, because of controversial or preliminary results, these techniques still require both basic and clinical research before their usefulness can be determined. Furthermore, unidimensional image with one single biomarker may not reflect the actual patient experience precisely enough.
4 Future research
Clinical research as well as standardization and validation of the objective markers described [1] are needed before the methods can reliably be applied to assess efficacy of opioid analgesia at individual patient level. The markers should be evaluated not only in healthy subjects and acute pain but also especially in chronic pain patients on different opioidergic treatments. Moreover, the specificity of these markers for analgesia should be addressed as sedation and emotional state may influence the results. Furthermore, the causes for between-subjects variability in the efficacy of opioid analgesia, and the genetic determinants of this variation [3] should also be taken into account in the validation process. This review gives a good starting point for many future trials.
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2016.10.001.
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Conflict of interest: None declared.
References
[1] Fischer IW, Hansen TM, Lelic D, Brokjær A, Frøkjær JB, Christrup LL, Olesen AE. Objective methods for the assessment of the spinal and supraspinal effects of opioids. Scand J Pain 2017;14:15–24.Suche in Google Scholar
[2] Brokjær A, Olesen AE, Kreilgaard M, GraversenC, Gram M, Christrup LL, Dahan A, Drewes AM. Objective markers of the analgesic response to morphine in experimental pain research. J Pharmacol Toxicol Methods 2015;73: 7–14.Suche in Google Scholar
[3] Nishizawa D, Hayashida M, Nagashima M, Koga H, Ikeda K. Genetic polymorphisms and human sensitivity to opioid analgesics. Methods Mol Biol 2010;617:395–420.Suche in Google Scholar
© 2016 Scandinavian Association for the Study of Pain
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