**6. Challenging issues and inconsistencies in NIBS**

NIBS is rapidly emerging as an intervention proposed for wide-ranging neurological and psychiatric disorders. However, tDCS studies have recently been scrutinized due to reported high degree of variability in effectiveness in published studies to date [89]. Evidence on the therapeutic use of both tDCS and newer methodologies like tACS are currently very limited, and the optimal parameters for use have yet to be fully elucidated. Many have suggested that there is a currently a general lack of understanding of the mechanisms by which these interventions are effective. However, tDCS has several advantages compared to the better investigated rTMS including ease of use, portability, and reduced expense [90], which support further investigation into the potential of tDCS in the treatment of pain.

Despite this, there is increasing evidence that NIBS are effective in the modulation of experimentally induced pain [91] as well as chronic pain conditions although the caveat to this is that there is reported variability in responsiveness across studies and individuals in both experimental and clinical studies. This efficacy of NIBS for experimental pain challenges the previously held understanding that neurostimulation devices act solely by interfering with the long-term maladaptive plasticity associated with chronic pain. Instead, it points toward a general lack of sufficient mechanistic understanding as to how NIBS modulates pain and how this modulation differs across individuals [92]. Moves toward characterizing differing individual "pain phenotypes," based on a battery of quantitative sensory testing, may provide insights into why some individuals respond to NIBS [7]. The use of protocols designed to give insights into an individual's endogenous descending modulation such as conditioned pain modulation (CPM) [93] may also be useful in conjunction with NIBS, in the same way that these protocols have been used when differentiating groups that respond to pharmacological treatment interventions. Another possible reason for the variability of the effects of rTMS on acute pain could be differential effects on each pain modality. For example, it is possible that rTMS may influence A- δ –fiber-mediated and C-fiber-mediated pain differently [94].
