(415) Effect of the benzodiazepine clobazam in chronic low back pain and experimental pain modalities: a randomized placebo-controlled crossover study

Abstract

GABAergic compounds enhance endogenous inhibitory control within the central nervous system and are therefore potentially useful in human pain conditions. Clobazam is an agonist at the benzodiazepine-binding site of GABA-A receptors. We investigated its effect on low back pain and experimental pain modalities in chronic low back pain. Forty-nine patients with chronic low back pain received a single oral dose of clobazam 20 mg and the active placebo tolterodine 1 mg in a double-blinded cross-over fashion. Pain intensity (0-10) (primary endpoint) was measured in the supine and sitting position. Nine experimental pain modalities of pressure, electrical and thermal pain, including conditioned pain modulation, were applied at body sites distant to the low back. All assessments were made during 2 hours after drug intake. Pain intensity in the supine position was significantly lower after clobazam compared to placebo (60 minutes: 2.9 vs. 3.5, p=0.008; 90 minutes: 2.7 vs. 3.3, p=0.024; 120 minutes: 2.4 vs. 3.1, p=0.005). Pain intensity in the sitting position was not significantly different between the groups. No effect on experimental pain tests was observed. The results are suggestive for an analgesic effect of clobazam in low back pain. The lack of effect in the sitting position suggests that GABAergic modulation may be less effective during mechanical strain of injured structures that may occur in the sitting position; the effect in the supine position suggests that GABAergic modulation is more effective at rest, when central sensitization processes may predominate over peripheral nociception. The lack of effect on experimental pain modalities suggests that GABAergic compounds may not be effective on non-sensitized neural pathways that are not functionally connected to the site of injury. The finding of the present study encourages pharmacologic research on GABAergic compounds that are devoid of tolerance and sedation. Funded by the Swiss National Science Foundation.