Here we demonstrate that 5% Lidocaine patch reduces the magnitude of CBP through a mechanism that cannot be distinguished from the effects of the placebo patch. However, pain intensity was reduced in a significant proportion of subjects in the 5% Lidocaine and placebo treated groups. These findings indicate that the therapeutic effectiveness of 5% Lidocaine observed in other back pain studies was due to the potent placebo properties of the patch itself and not due to a pharmacological action of the drug.
Placebo controlled clinical trials have shown that systemic or topical Lidocaine reduces severity of chronic post-herpetic neuropathy, neuropathic pain, and for pain associated with inflammatory bowel disease [4, 26, 27]. This is the first placebo controlled clinical trial for 5% Lidocaine in chronic back pain and our findings indicate that the analgesic effects of 5% Lidocaine patch on CBP could not be distinguished from the placebo patch. In addition, there was a generalized decrease in sensory and affective pain qualities after treatment, but even in these measurements, the 5% Lidocaine treated group was not significantly different from the placebo group. In other clinical conditions such as painful diabetic neuropathy and complex regional pain syndrome, the drug showed greater benefit than placebo, but the effectiveness was variable ranging from 29% to 80% of studied cases [11, 16–19].
The mode of action of topical Lidocaine is not clear and clearly shows inter individual variability in responsiveness between patients with neuropathic pain syndromes and also in evoked pain responses in healthy subject after treatment. In one study, several patients with complete loss of electric nerve function and marked subepidermal nerve-fiber plexus denervation in the peripheral limb showed a response to the Lidocaine patch . An important implication of this study was that electric nerve function is not an essential for the mechanisms of 5% Lidocaine therapeutic action. Even in healthy subjects, 5% Lidocaine was not more effective than placebo in treating experimental pain and innocuous sensation including heat evoked pain, mechanical pain and capsaicin induced pain [11–13]. These negative findings led to the speculation that the 5% Lidocaine is too low a dose to effectively block healthy nociceptors, but may block pathological activity associated with upregulated sodium channels that result in neuropathic pain [11, 14]. The Lidocaine patch has been suggested to affect neuropathic pain by a local non selective stabilization of sodium channels on cutaneous afferents at or near the site of application [1, 9]. The findings of the present study corroborated by other studies raise some questions in this regard and show that Lidocaine was not more effective than placebo in treating chronic back pain that does have a significant contribution from neuropathic sources.
The 5% Lidocaine patch is an off label treatment for chronic back pain. This treatment has been increasingly advocated due to its purported effectiveness and is recommended over other treatments due to fewer side effects [19, 28, 29]. The confidence in the efficacy of the 5% Lidocaine patch especially for treating CBP is based mainly on open labelled trials and the role of placebo analgesia in mediating the actions of the 5% Lidocaine patch had not been tested before. Our findings suggest that the 5% Lidocaine patch acts as potent placebo and has no detectable pharmacological effect in either pain report or in brain activity. The fact that a nearly equal number of subjects in the Lidocaine and placebo arm reported a marked decrease in pain indicates that the effects of just the patch itself irrespective of the presence of drug can produce analgesia through endogenous pain regulatory mechanisms associated with placebos [30–32]. A putative placebo mechanism in reducing pain is reflected by the fact that only the patch treated group as a whole showed a significant reduction in pain intensity when compared to a group of CBP patients that were not given any treatment. This observation explains the positive findings we had reported in a previous report where in an open labelled trial, the 5% Lidocaine patch was effective in reducing pain intensity on average accompanied with related changes in pain related brain activation patterns after treatment . However, in the present and in the preliminary study, we observed a marked reduction in clinical pain after treatment that suggests that the patch induces a potent placebo analgesia.
However, the present study also demonstrates that not all subjects responded with analgesia to the patch, and the percent change in pain was negligible in half of the subjects. Thus, the placebo effect induced by the patches is subject to a prominent inter-individual variability and this extent of variability has not been observed in previous placebo studies [31, 33–35]. This could be because most placebo studies have studied healthy subjects and placebo responses in clinical populations may be affected by disease chronicity. Another prominent factor is that unlike most placebo studies where a group of subjects is conditioned to believe in the benefits of the treatment [36, 37], here all patch treated subjects were given similar open ended instructions that the treatment may or may not reduce their pain. Thus the psychobiological mechanisms that lead to reduction or no reduction in pain would be reflective of each individuals own expectations, belief in the treatment and anxiety about the treatments potential benefits.
One limitation of this study is that the number of subjects is lower than what would be required for a clinical trial. However, corroborated by other studies, these findings indicate that a large sample size would result in a similar outcome. A calculation for the required sample size to achieve a clinically relevant change in pain of 20 % combined with the present findings required 536 subjects to achieve a desired power of 0.85 (large effect size). Such a large number of chronic back pain subjects would be extremely difficult if not unachievable to recruit for an fMRI study. Nevertheless, additional studies are needed that test the effects of the 5% Lidocaine patch against a placebo to arrive at a solid conclusion regarding the efficacy of this treatment in chronic back pain.
Recently, the 5% Lidocaine patch has emerged as first line therapy and since side effects are lower than oral or systemic doses, its use has become popular especially in geriatric populations. Our findings raise some important considerations since even though the 5% Lidocaine had no direct effect; the patch itself induces analgesia that is two to three folds higher than the accepted clinical level of 20% , but a discussion about the ethics of using placebos that produce strong analgesic effects is beyond the scope of the objectives of this study. This study brings to bear “the elephant in the room” issue relating to the ever present placebo effect in analgesic trials. This study also raises the need for more consideration into whether the clinical use of the Lidocaine patch in CBP is warranted. Overall, based on these findings, we conclude that the 5% Lidocaine patch has no drug mediated action on intensity of CBP; however, it does reduce pain intensity in more than 50% of subjects that is most likely due to a placebo effect. Our findings suggest that the patch is a potent agent for inducing placebo analgesia.