Mechanism of Analgesic Effect on Prolonged Continuous Theta Burst Stimulation
- Conditions
- Chronic PainrTMS
- Interventions
- Drug: SalineDevice: pcTBS of M1Device: pcTBS of DLPFCDevice: SHAM stimulation
- Registration Number
- NCT05360030
- Lead Sponsor
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- Brief Summary
It has been shown that prolonged continuous theta burst stimulation (pcTBS) , a relatively new repetitive transcranial magnetic simulation (rTMS) protocol, of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) decreases pain in healthy volunteers, in various experimental models. In addition, rTMS of M1 has also been shown to have analgesic effects in various chronic pain conditions, including neuropathic pain.The mechanisms underlying rTMS-induced analgesia remain unclear. Functional neuroimaging studies have shown that rTMS of M1 and DLPFC induces changes in the activity of cortical and subcortical structures involved in pain processing and modulation. Endogenous opioids and e N-methyl-D-aspartate (NMDA) receptor are known to play a major role in these processes. The investigator hypothesized that the endogenous opioids systems (EOS) and NMDA receptor might be involved in the analgesic action of pcTBS. In the first part,the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, the intensity of pain induced by capsaicin were used to evaluate the analgesic effects of pcTBS. If naloxone does not reverse the analgesic effect of pcTBS,The volunteers will be invited to participant the second part of the study, which the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after Ketamine treatment.
- Detailed Description
This study comprised 3 parallel arms corresponding to 3 types of stimulation: active stimulation of M1, active stimulation of DLPFC-pcTBS, and sham stimulation (of M1 or DLPFC). Volunteers were randomly assigned to the 3 arms. In the first part, these volunteers participated in 2 experimental sessions 1 weeks apart, in which we compared the effects of naloxone and placebo (saline), administered according to a randomized, double-blind crossover design, on pcTBS-induced analgesia. Each experimental session started with the determination of baseline pain intensity and cortical excitability as well as plasma opioid peptide concentrations. Ten minutes before pcTBS (of M1, DLPFC, or sham), the volunteer received an intravenous bolus followed by a continuous infusion of either placebo (ie, saline) or naloxone, which was continued throughout the rTMS session (2 minutes). The participant was then allowed to rest for 60 minutes. Posttreatment pain intensity, cortical excitability and plasma opioid peptide concentrations will be determined by the same procedure used at baseline.In the second part, ketamine will be delivered the same as the first part.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
1）woman or man over 18 and under 85 years old; 2）Clinical diagnosis of physical and mental health people; 3) able to cooperate in completing questionnaire.
1)Clinical diagnosis of 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) Any difficulty to fill out questionnaires (due to language or cognitive problems);
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description active stimulation of M1 Ketamine Hydrochloride 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. SHAM stimulation Ketamine Hydrochloride 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 active stimulation of DLPFC Ketamine Hydrochloride pcTBS was administered to the left DLPFC 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. active stimulation of M1 Saline 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. active stimulation of M1 pcTBS of M1 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. active stimulation of DLPFC pcTBS of DLPFC pcTBS was administered to the left DLPFC 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. SHAM stimulation Saline 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 active stimulation of DLPFC Saline pcTBS was administered to the left DLPFC 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. SHAM stimulation Naloxone 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 SHAM stimulation SHAM stimulation 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 active stimulation of M1 Naloxone 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. active stimulation of DLPFC Naloxone pcTBS was administered to the left DLPFC 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.
- Primary Outcome Measures
Name Time Method pain intensity at baseline Baseline pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) at baseline.
pain intensity at the posttreatment of pcTBS through study completion, an average of 8 months pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) at the posttreatment of pcTBS.
- Secondary Outcome Measures
Name Time Method Motor-evoked potential (MEP) through study completion, an average of 8 months Corticospinal excitability will be 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 will be 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).
Maximum plasma concentration of opioid peptide at baseline baseline plasma opioid peptide concentrations will be measured using ELISA at baseline.
Maximum plasma concentration of opioid peptide at the posttreatment of pcTBS through study completion, an average of 8 months plasma opioid peptide concentrations will be measured using ELISA at the last posttreatment of pcTBS.
Trial Locations
- Locations (1)
The second affiliated hospital of Zhejiang University hangzhou
🇨🇳Hangzhou, Zhejiang, China