Our results show that 10 daily sessions of 2 mA, 20 min tDCS of left M1 or DLPFC can both induce significant improvements with respect to pain and quality of life in patients with fibromyalgia. These findings are consistent with our previous study of tDCS in patients with fibromyalgia--where 5 daily sessions of M1 tDCS also induced a significant pain reduction. However, in contrast to our previous study where pain scores were noted to take an upward slope at two weeks after treatment completion, here we show that 10 sessions of M1 tDCS can be effective in maintaining the observed diminishment of pain scores for up to 60 days. This difference is in keeping with an rTMS study in patients with fibromyalgia, which shows that 10 daily sessions of 10Hz rTMS applied to the motor cortex can induce similarly long-lasting improvements in pain and measures of quality of life (38
). Interestingly, the analgesic effects of the repeated sessions of rTMS were significant only after 5 days of stimulation.
These results are interesting as they underscore the impact of the number of treatment sessions in inducing and maintaining long-lasting clinical effects. Indeed, previous tDCS studies have come to a similar conclusion: Five daily sessions of tDCS in stroke patients yields greater improvements in motor function than a single session alone (39
); and, rTMS studies corroborate this session-number dependent efficacy trend: more sessions results in longer-lasting or more significant effects (40
). In addition, the importance lies not only in the total number of sessions administered, but also in their temporal proximity: 4 weekly sessions of tDCS in stroke patients does not result in changes that are significantly different from single session therapy (39
). Therefore, these findings suggest that tDCS induces a cumulative effect that is maximized by consecutive sessions.
tDCS is believed to induce clinical effects through the modulation of synaptic connections (43
). Nitsche et al. have shown that anodal stimulation of sufficient duration can enhance cortical excitability beyond the stimulation period (20
). Further studies have revealed that these changes in post-tDCS cortical excitability are intimately dependent on Na+ channel and NMDA receptor activity (44
) and that acetylcholine plays an important role in the consolidation of this neuroplasticity (46
). These results suggest that long term potentiation of new adaptive synaptic connection is what underlies the improvements in working memory (27
), motor function (39
), and pain modulation (47
) that have been attributed to tDCS. Because LTP underlies the mechanism behind the long-lasting effects of repeated sessions of tDCS, it is therefore not surprising that the changes in cortical excitability and synaptic connections induced by tDCS are prone to extinction and that they can be reinforced with longer and/or additional treatment sessions. Indeed, the difference between our results with 10 sessions of tDCS vs. 5 daily sessions may be attributed to greater synaptic strengthening.
In addition to demonstrating the efficacy of M1 tDCS in relieving pain in fibromyalgia, our study here also demonstrates a potential role for DLPFC stimulation. Whereas our previous study failed to show a significant effect for DLPFC stimulation, here 10 sessions of DLFPC stimulation significantly diminished pain scores compared to sham stimulation. Thus, it is possible that DLPFC is also useful but it is inevitably less effective than M1 for the treatment of fibromyalgia-associated pain. Mechanistically, M1 stimulation produces an analgesic effect by modulating the sensory aspects of pain, while DLPFC stimulation mediates its effects by modulating affective-emotional networks regulating the unpleasantness associated with pain (11
). Pain in fibromyalgia has been associated with abnormal information processing characterized by a lack of inhibitory control over somatosensory processing (7
); thus, it appears appropriate that M1 tDCS would have a more primary analgesic effect in this population.
The treatment protocols resulted in no change to tender points or measures of depression or anxiety as compared to sham stimulation; these parameters may be secondary to central pain in fibromyalgia. In addition we found no significant correlations between baseline characteristics and response to treatment, yet this might be due to low power to perform these correlations.
Here we show that 10 daily sessions of M1 and DLPFC tDCS both generate clinical improvements in patients with fibromyalgia, but that only M1 stimulation results in long-lasting clinical benefits as assessed at 30 and 60 days after the end of treatment. This study demonstrates the importance of the duration of the treatment period, suggesting that protocols with 10 daily sessions of tDCS would result in more long lasting outcomes than protocols with only 5 daily sessions. Furthermore, this study supports the findings of a similarly designed rTMS trial (38
), although it should be noted that the magnitude of the effect of 10 sessions of tDCS appears to be greater than the respective rTMS trial— nevertheless, this needs to be compared in a head to head comparison trial of tDCS vs. rTMS using the same study population. Noninvasive forms of brain stimulation hold great promise, yet further studies are indicated to determine the role of maintenance therapy in treatment planning.