**Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients**

**Sascha Freigang 1, \* , Christian Lehner 1 , Shane M. Fresnoza 2,3 , Kariem Mahdy Ali 1 , Elisabeth Hlavka 1 , Annika Eitler <sup>1</sup> , Istvan Szilagyi 4 , Helmar Bornemann-Cimenti 5 , Hannes Deutschmann 6 , Gernot Reishofer 6 , Anže Berlec <sup>1</sup> , Senta Kurschel-Lackner 1 , Antonio Valentin 7 , Bernhard Sutter 1 , Karla Zaar <sup>1</sup> and Michael Mokry 1**

	- Institute of Psychology, University of Graz, 8010 Graz, Austria; shane.fresnoza@uni-graz.at

2


**Abstract:** Repetitive transcranial stimulation (rTMS) has been shown to produce an analgesic effect and therefore has a potential for treating chronic refractory pain. However, previous studies used various stimulation parameters (including cortical targets), and the best stimulation protocol is not yet identified. The present study investigated the effects of multi-session 20 Hz (2000 pulses) and 5 Hz (1800 pulses) rTMS stimulation of left motor cortex (M1-group) and left dorsolateral prefrontal cortex (DLPFC-group), respectively. The M1-group (*n* = 9) and DLPFC-group (*n* = 7) completed 13 sessions of neuronavigated stimulation, while a Sham-group (*n* = 8) completed seven sessions of placebo stimulation. The outcome was measured using the German Pain Questionnaire (GPQ), Depression, Anxiety and Stress Scale (DASS), and SF-12 questionnaire. Pain perception significantly decreased in the DLPFC-group (38.17%) compared to the M1-group (56.11%) (*p* ≤ 0.001) on the later sessions. Health-related quality of life also improved in the DLPFC-group (40.47) compared to the Sham-group (35.06) (*p* = 0.016), and mental composite summary (*p* = 0.001) in the DLPFC-group (49.12) compared to M1-group (39.46). Stimulation of the left DLPFC resulted in pain relief, while M1 stimulation was not effective. Nonetheless, further studies are needed to identify optimal cortical target sites and stimulation parameters.

**Keywords:** chronic pain; low back pain; repetitive transcranial magnetic stimulation; neuromodulation; dorsolateral prefrontal cortex; primary motor cortex
