Analgesic effect of clobazam in chronic low‐back pain but not in experimentally induced pain

Schliessbach, Jürg; Vuilleumier, Pascal Henri; Siegenthaler, Andreas; Bütikofer, Lukas; Limacher, Andreas; Jüni, Peter; Zeilhofer, Hanns Ulrich; Arendt-Nielsen, Lars; Curatolo, Michele

doi:10.1002/ejp.1032

Cited by 14 publications

(9 citation statements)

References 25 publications

(45 reference statements)

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“…Forty‐nine patients were therefore analysed (29 women, mean age 54.3 years, SD 15.8). A significant analgesic effect was found in the supine, but not in the sitting position (treatment effect compared to placebo: 0.7, 95%‐CI 0.2 to 1.1, p = 0.003), which is the object of a separate publication (Schliessbach et al., ). For supine pain, there were 29 responders in the verum session vs. 20 in the placebo session.…”

Section: Resultsmentioning

confidence: 95%

“…These drugs were chosen to cover multiple modes of analgesic action. Oxycodone is a potent agonist at peripheral and central opioidergic pathways, imipramine is a modulator of noradrenergic neurotransmission and serotonergic neurotransmission in the central nervous system, and clobazam modulates spinal nociceptive inhibitory GABA‐ergic pathways (Zeilhofer et al., ; Vuilleumier et al., ; Schliessbach et al., ).…”

Section: Introductionmentioning

confidence: 99%

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Predicting drug efficacy in chronic low back pain by quantitative sensory tests

Schliessbach

Siegenthaler

Bütikofer

et al. 2018

European Journal of Pain

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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Predicting drug efficacy in chronic low back pain by quantitative sensory tests

Schliessbach

Siegenthaler

Bütikofer

et al. 2018

European Journal of Pain

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“…It was registered with clinicaltrials.gov (NCT01179828) and approved by the local ethics committee (KEK 213-09). The detailed study protocol [7] and results from another substudy [8] have been published. All participants gave written informed consent prior to enrolment.…”

Section: Methodsmentioning

confidence: 99%

Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain

Schliessbach

Siegenthaler

Bütikofer

et al. 2017

Scandinavian Journal of Pain

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AbstractIntroductionQuantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain.MethodsIn this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15 mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2 h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≤30% pain reduction) was set as reference variable and changes in QST from baseline were set as classifiers.ResultsSignificant analgesic effect on low-back pain as well as anti-nociceptive effects for almost all QST parameters were observed. The QST with the highest area under the curve were heat pain detection threshold (0.65,95%-CI 0.46 to 0.83), single-stimulus electrical pain threshold (0.64,95%-CI 0.47 to 0.80) and pressure pain detection threshold (0.63,95%-CI 0.48 to 0.79).ConclusionsThe results suggest that anti-nociceptive effects assessed by QST fairly reflect clinical efficacy of oxycodone on low-back pain. Pressure pain detection threshold, heat pain detection threshold and single-stimulus electrical pain threshold may be more suitable to sort out potential non-responders rather than identifying potential responders to opioid medication. Future pre-clinical human research may consider these results when investigating the analgesic effect of opioid agonists by means of QST.

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“…Noteworthy, clinical trials performed on chronic lower-back pain patients have shown that CBZ and their metabolites are able to generate analgesia in humans (Besson et al, 2015;Schliessbach et al, 2017).…”

Section: Gaba a Rsmentioning

confidence: 99%

Pentameric Ligand-Gated Ion Channels as Pharmacological Targets Against Chronic Pain

et al. 2020

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Chronic pain is a common detrimental condition that affects around 20% of the world population. The current drugs to treat chronic pain states, especially neuropathic pain, have a limited clinical efficiency and present significant adverse effects that complicates their regular use. Recent studies have proposed new therapeutic strategies focused on the pharmacological modulation of G-protein-coupled receptors, transporters, enzymes, and ion channels expressed on the nociceptive pathways. The present work intends to summarize recent advances on the pharmacological modulation of pentameric ligandgated ion channels, which plays a key role in pain processing. Experimental data have shown that novel allosteric modulators targeting the excitatory nicotinic acetylcholine receptor, as well as the inhibitory GABA A and glycine receptors, reverse chronic painrelated behaviors in preclinical assays. Collectively, these evidences strongly suggest the pharmacological modulation of pentameric ligand-gated ion channels is a promising strategy towards the development of novel therapeutics to treat chronic pain states in humans.

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Analgesic effect of clobazam in chronic low‐back pain but not in experimentally induced pain

Abstract: Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.

Cited by 14 publications

References 25 publications

Predicting drug efficacy in chronic low back pain by quantitative sensory tests

Predicting drug efficacy in chronic low back pain by quantitative sensory tests

Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain

Pentameric Ligand-Gated Ion Channels as Pharmacological Targets Against Chronic Pain

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