Cortical stimulation for chronic pain: from anecdote to evidence

Epidural stimulation of the motor cortex (eMCS) was devised in the 1990's, and has now largely supplanted thalamic stimulation for neuropathic pain relief. Its mechanisms of action involve activation of multiple cortico-subcortical areas initiated in the thalamus, with involvement of endogenous opioids and descending inhibition toward the spinal cord. Evidence for clinical efficacy is now supported by at least seven RCTs; benefits may persist up to 10 years, and can be reasonably predicted by preoperative use of non-invasive repetitive magnetic stimulation (rTMS). rTMS first developed as a means of predicting the efficacy of epidural procedures, then as an analgesic method on its own right. Reasonable evidence from at least six well-conducted RCTs favors a significant analgesic effect of high-frequency rTMS of the motor cortex in neuropathic pain (NP), and less consistently in widespread/fibromyalgic pain. Stimulation of the dorsolateral frontal cortex (DLPFC) has not proven efficacious for pain, so far. The posterior operculo-insular cortex is a new and attractive target but evidence remains inconsistent. Transcranial direct current stimulation (tDCS) is applied upon similar targets as rTMS and eMCS; it does not elicit action potentials but modulates the neuronal resting membrane state. tDCS presents practical advantages including low cost, few safety issues, and possibility of home-based protocols; however, the limited quality of most published reports entails a low level of evidence. Patients responsive to tDCS may differ from those improved by rTMS, and in both cases repeated sessions over a long time may be required to achieve clinically significant relief. Both invasive and non-invasive procedures exert their effects through multiple distributed brain networks influencing the sensory, affective and cognitive aspects of chronic pain. Their effects are mainly exerted upon abnormally sensitized pathways, rather than on acute physiological pain. Extending the duration of long-term benefits remains a challenge, for which different strategies are discussed in this review.