Lidocaine patch (5%) is no more potent than placebo in treating chronic back pain when tested in a randomised double blind placebo controlled brain imaging study

Javeria A Hashmi, Marwan N Baliki, Lejian Huang, Elle L Parks, Mona L Chanda, Thomas Schnitzer, A Vania Apkarian, Javeria A Hashmi, Marwan N Baliki, Lejian Huang, Elle L Parks, Mona L Chanda, Thomas Schnitzer, A Vania Apkarian

Abstract

Background: The 5% Lidocaine patch is used for treating chronic neuropathic pain conditions such as chronic back pain (CBP), diabetic neuropathy and complex regional pain syndrome, but is effective in a variable proportion of patients. Our lab has reported that this treatment reduces CBP intensity and associated brain activations when tested in an open labelled preliminary study. Notably, effectiveness of the 5% Lidocaine patch has not been tested against placebo for treating CBP. In this study, effectiveness of the 5% Lidocaine patch was compared with placebo in 30 CBP patients in a randomised double-blind study where 15 patients received 5% Lidocaine patches and the remaining patients received placebo patches. Functional MRI was used to identify brain activity for fluctuations of spontaneous pain, at baseline and at two time points after start of treatment (6 hours and 2 weeks).

Results: There was no significant difference between the treatment groups in either pain intensity, sensory and affective qualities of pain or in pain related brain activation at any time point. However, 50% patients in both the Lidocaine and placebo arms reported a greater than 50% decrease in pain suggesting a marked placebo effect. When tested against an untreated CBP group at similar time points, the patch treated subjects showed significantly greater decrease in pain compared to the untreated group (n = 15).

Conclusions: These findings suggest that although the 5% Lidocaine is not better than placebo in its effectiveness for treating pain, the patch itself induces a potent placebo effect in a significant proportion of CBP patients.

Figures

Figure 1
Figure 1
Pain did not differ between chronic back pain (CBP) patients treated with 5% lidocaine patches or with patches containing no active drug (placebo). A. Variation of CBP pain with treatment type and treatment duration. Treatment duration, but not type, significantly decreased CBP pain. B-E. Effect of treatment type and duration on sensory (range 0-33) and affective scores (range 0-12) obtained on the McGill pain Questionnaire (MPQ). Sensory and affective scores decreased with treatment duration for both types of treatment. Error bars represent SEMs. * p ≪ 0.05, ** p ≪ 0.01 differences from baseline.
Figure 2
Figure 2
Different groupings for brain activity for spontaneous fluctuations of pain of CBP calculated for brain scans collected at baseline. Coordinates x = 8, y = 56, z = 20 for A-D (top row are sagittal, middle horizontal, and bottom coronal slices; middle and bottom rows: left side is left hemisphere). A. Whole-group average brain activity for rating spontaneous pain of CBP patients (n = 30 subjects). Brain activity was limited to medial prefrontal cortex (BA 9) and the genual anterior cingulate cortex (BA 32). B. Contrast between activity for rating spontaneous pain of CBP and rating length of a bar varying in time (control for visual, motor, and task demands; paired t-statistic n = 30 subjects) identifies the same brain activity as in A. C and D. Brain activity was similar between placebo (C) and lidocaine (D) treated groups for spontaneous pain of CBP at baseline (n = 15 subjects per group), and closely matched whole-group activity shown in activity and contrast maps were generated using random-effects statistics with z score ≫ 2.3 and cluster threshold p ≪ 0.01, corrected for multiple comparisons.
Figure 3
Figure 3
Pain for treated and observed groups, and pain when treated group was subdivided based on pain of CBP decreasing (CBPd) or persisting (CBPp) after 2 weeks. A. Pain at baseline and after 2-weeks (visual analog score, VAS, 0-10 score) in CBP patients who received no interventions or treatment instructions, CBP observed (n = 15), in contrast to the patients who participated in the clinical trial for an ineffective treatment, CBP treatment (n = 30). The two groups started at a similar intensity of back pain but only the CBP treatment group showed decrease in back pain after two weeks. Error bars represent SEMs. * p ≪ 0.05. B. Back pain intensity, in CBPd and CBPp groups, as a function of treatment duration. A median split shows that on average the group that showed absolute pain change more than the median had significantly lower pain at the 2 week time point.
Figure 4
Figure 4
Consort 2012 flowchart.

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