Neuropathic pain is frequent and drugs relieves only 50% of the patients. Repetitive transcranial magnetic stimulation (rTMS) at high frequency (HF, usually 10Hz) applied on the primary motor cortex (M1) is an effective treatment of neuropathic pain. For the treatment of chronic pain, the 'classical' HF-rTMS protocol (CHF-rTMS) include one daily session for one or two weeks as an induction phase of treatment followed by a weekly session to produce analgesic effects. However, another type of protocol is based on a more spaced repetition of HF-rTMS sessions (SHF-rTMS), including intervals of several days or weeks between two sessions, but also resulting in a significant pain relief. However, CHF-rTMS and SHF-rTMS have never been compared regarding their analgesic efficacy.
Alongside with pain, depression is the other clinical condition for which HF-rTMS is proposed as an effective therapeutic strategy. Another type of rTMS paradigm, called "accelerated intermittent theta burst stimulation" (ACC-iTBS) protocol has been recently proposed for the treatment of depression, combining a high number of pulses delivered per session and a high number of short-duration sessions grouped into a few days of stimulation. However, this type of protocol has never been applied for the treatment of chronic pain patients.
Thus, for the first time we propose to compare in a pilot study the efficacy of three different rTMS protocols for the treatment of chronic neuropathic: CHF-rTMS, SHF-rTMS, and ACC-iTBS. In this study, two protocols two rTMS protocols (CHF-rTMS and ACC-iTBS) will share the same high total number of TMS pulses (i.e. 30 000 pulses) versus an rTMS protocol (SHF-rTMS) based on a lower total number of TMS pulses (i.e. 6 400 pulses), while one protocol (CHF-rTMS) will include a higher number of days of stimulation (i.e. 10 days) compared to the two other protocols (ACC-iTBS and SHF-rTMS) (i.e. 4 days). In all cases, the motor cortical target and the intensity of stimulation will the same.
Thus, this study will be able to appraise the respective influence of the number of pulses delivered (the higher the number, the greater the effect) and the number of sessions (the higher the number, the more restrictive the implementation of treatment). That is to say that the new ACC-iTBS protocol could be an optimal compromise of a more efficacious and more easy-to-perform rTMS protocol for the treatment of patients with chronic pain.
(1) existence of a definite peripheral neuropathy on both clinical and neurophysiological grounds, present for at least 6 months;
(2) neuropathic pain clearly related to the neuropathy, as defined by a score ≥ 4/10 on the questionnaire "Douleur Neuropathique en 4 Questions" (DN4) ;
(3) a score ≥ 4/10 on a 0-10 numerical rating scale (NRS) concerning the average intensity of daily ongoing pain;
(4) age between 18 and 80 years;
(1) concomitant neurological (neurodegenerative disorders, migraine, epilepsy, stroke, tumor) or psychiatric illness;
(2) contraindications related to TMS (intracranial ferromagnetic material);
(3) drug-resistant or active epilepsy.
Parallel
transcranial magnetic stimulation (TMS)
DeviceA brief, short, and repeated magnetic field is generated by 2 copper coils inducing an electric current that will propagate within the targeted cortical areas.
Interference Scale of the short form of the Brief Pain Inventory (BPI)
The 7-item Interference Scale of the short form of the Brief Pain Inventory measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. It uses a 0 to 10 numeric rating scales for each item rating. The minimum score is 0 (no interference of pain on daily living activities, ie better outcome) and the maximum score is 70 (maximal interference of pain on daily living activities, ie worse outcome).
Average intensity of daily ongoing pain on a 0-10 numeric rating scale (NRS)
The 0-10 numeric rating scale (NRS) measures the average intensity of daily ongoing pain. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 10 (maximal pain, ie worse outcome).
Average intensity of daily ongoing pain on a 0-5 verbal rating scale (VRS)
The 0-5 verbal rating scale (VRS) measures the average intensity of daily ongoing pain. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 5 (unbearable pain, ie worse outcome).
Patient global impression of change (PGIC)
The 7-item patients' clinical global impression (PGIC) will be used to evaluate the subjective improvement or deterioration (from very much improved to very much deteriorated)
Symptomatic profile of neuropathic pain on the Neuropathic Pain Symptom Inventory (NPSI)
The Neuropathic Pain Symptom Inventory (NPSI) measures the neuropathic pain symptoms specifically. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 100 (maximal neuropathic pain symptoms, ie worse outcome).
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