Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain

Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain

Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response. A noninvasive brain-stimulation method called transcranial magnetic stimulation (TMS) has garnered interest as an alternative treatment for intractable NP potentially through inducing therapeutic brain plasticity.Indeed, high-frequency (≥ 5 Hz) Repetitive TMS (rTMS) over the primary motor cortex (M1) is suggested to be able to reduce neuropathic pain in randomized controlled studies.Overall, the clinical application of rTMS in chronic pain is still limited by the response rate,the investigation of rTMS protocols is important for improving rTMS analgesia. Theta burst stimulation (TBS) mimics the bursts of neuronal firing which results in robust long-term potentiation. Continuous TBS (cTBS) is designed to decrease excitability, whereby prolonged cTBS (pcTBS, i.e. multiple cTBS being delivered continuously) has recently been demonstrated to increase excitability. More importantly, pcTBS was found to have comparable or even better analgesic effects than standard 10 Hz rTMS. These findings together call for more studies to validate the analgesic efficacy of pcTBS.

In this study, the investigators aim to assess and compare the efficacy of prolonged continuous theta burst stimulation (pcTBS) with 10HZ rTMS in NP patients.

The investigators designed a randomized, double-blind, sham-controlled study at 1 center. fifty NP patients were randomly assigned to 3 groups. A series of 5 daily pcTBS(1200 pulses/session) or 10-Hz rTMS (1500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patients.

Inclusion Criteria:

• (1)woman or man over 18 and under 70 years old; （2）pain fulfilling the criteria for probable or definite peripheral neuropathic pain ; (3) pain for at least 3 months, continuous pain (at least four days per week), at least moderate intensity (≥ 4/10 assessed by VAS) ; (4) stable pharmacological treatment for pain at least 2 weeks before inclusion; (5) able to cooperate in completing questionnaire.

Exclusion Criteria:

• (1) Any clinically significant or unstable ongoing medical or psychiatric disorder including major depression; (2) History of substance abuse (alcohol, drugs); (3) Past treatment with repetitive transcranial magnetic stimulation (rTMS); (4) Contraindications to rTMS (previous severe head trauma or neurosurgical intervention, past or current epilepsy, active brain tumor, intracranial hypertension, implanted ferromagnetic devices, e.g., cardiac pacemaker, neurostimulator, or cochlear implants); (5) other type of pain more severe than neuropathic pain; (6) Any difficulty to fill out questionnaires (due to language or cognitive problems); (7) impossibility to be followed during the time course of the study;