Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: pcTBS pcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline. |
Device: Repetitive transcranial magnetic stimulation
Participants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays
|
| Active Comparator: 10HZ rTMS The rTMS protocol included 15 trains of 10-second stimulation given at 10 Hz to the left M1 at 80% resting motor threshold (RMT), with the inter-train interval being set to 50 seconds (1500 pulses) |
Device: Repetitive transcranial magnetic stimulation
Participants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays
|
| Sham Comparator: Sham The Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal |
Device: Sham stimulation
Participants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays
|
Outcome Measures
Primary Outcome Measures
- The mean change from baseline in pain intensity measured with the visual-analogic scale (VAS) [through study completion, an average of 8 months]
The primary outcome measure was the mean change from baseline over the course of 5 (group by time interaction) in average pain intensity measured with the visual-analogic scale (VAS) ( 0= no pain and 10= maximal pain). Baseline average pain intensity was assessed at inclusion then on the day of randomization, just before the first rTMS session (day 1) and corresponded to the average of these two values.
Secondary Outcome Measures
- Motor-evoked potential (MEP) [through study completion, an average of 8 months]
Corticospinal excitability was measured with MEP at rest of the first dorsal interosseous (FDI) muscle, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
- Cortical silent period (CSP) [through study completion, an average of 8 months]
Corticospinal excitability was measured with CSP during a sustained voluntary FDI muscle contraction, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
- The sensory dimension of pain and affective dimension of pain [through study completion, an average of 8 months]
The sensory dimension of pain (rated on 33) and affective dimension of pain (rated on 12) from the 15-items Short form of the McGill Pain questionnaire (SF-MPQ) .
- Pain interference scale [through study completion, an average of 8 months]
7 items rated from 0= does not interfere to 10= complete interference, total score 70 from the Brief Pain Inventory.
- Patients global impression of change [through study completion, an average of 8 months]
the 7 items Patients global impression of change (PGIC) (from very much worse to very much improved)
- The depression score [through study completion, an average of 8 months]
ranging from 0 to 13 with higher scores indicating more severe depression from the 13 items Beck Depression Inventory (BDI)
- release of neurotransmitters [through study completion, an average of 8 months]
Measured with magnetic resonance spectroscopy,MRS
Eligibility Criteria
Criteria
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;
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
- Study Chair: min yan, prof, The second affiliated hospital of Zhejiang University hangzhou
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-0751