Association between Neuropathic Pain and Depression: Focusing on the Transcranial Magnetic Stimulation As a Promising Treatment Approach

BACKGROUND: Neuropathic pain (NP) affects approximately 7% of the general population and is often accompanied by depressive symptoms with up to 85% of NP patients are suffering from comorbid depression (CD). The noninvasive neuromodulation technique of transcranial magnetic stimulation (TMS) is an established proven clinically effective nonpharmacological treatment for depression, and considered a highly promising option also for reducing the burden of NP by relieving pain perception and increasing patients' quality of life. In this article, we systematically review the various clinical protocols used in TMS treatments in patients suffering from NP and comorbid depression.

SUBJECTS AND METHODS: Using Scopus, Elsevier, and PubMed databases, our keyword search identified 639 articles, of which 22 were selected for detailed analysis based on the inclusion criteria and in consideration of the heterogeneous study design of the majority of small trials. We evaluated the clinical efficacy in NP and comorbid depression, in relation to various TMS protocol parameters including coil type, target brain area, locus of increased evoked motor potential, amplitude of stimulation, duration of session, number of sessions per day/month, as well as inter-session-intervals, number and frequency of trains, and number and frequency of pulses.

RESULTS: The most effective TMS protocols for treating comorbid NP and depression, as marked by decreased pain and depression scores proved to entail figure-of-8 coils targeting the primary motor area (M1), and applying at least ten daily rTMS sessions using high frequency stimulation (10-20 Hz) with a sub threshold intensity of 80-90% RMT and a total number of pulses of at least 1500 per session. Performing an additional maintenance phase after the acute treatment phase may strengthen and prolong the therapeutic effects of rTMS.

CONCLUSIONS: Our database analysis suggests that a specific combination of TMS parameters is most effective for treating NP and comorbid depression. Although results are promising, the heterogeneity within the literature is such that many underpowered studies contribute rather little to the outcome, as evident by our inclusion / exclusion analysis. Moreover, we see a need for consensus on clinical protocols and inclusion of much larger clinical samples. Furthermore, we conclude that future research should entail advanced TMS procedures with multiple brain region stimulation (sequential or concurrent), and address issues of TMS maintenance and improved coil engineering for targeting deeper structures.