2、Deep brain stimulation(DBS)

Deep  brain  stimulation (DBS)  has  shown  benefits  for  movement  disorders      such as Parkinson's    disease, tremor and dystonia and     affective     disorders     such asdepression, obsessive-compulsive disorder, Tourette syndrome, chronic pain and cluster headache。 Since DBS can directly change the brain activity in a controlled manner, it is used to map fundamental mechanisms of brain functions along with neuroimaging methods。 A simple DBS system consists of two different parts。 First, tiny microelectrodes are implanted in the brain to deliver stimulation pulses to the tissue。 Second, an electrical pulse generator (PG) generates stimulation pulses, which is connected to the electrodes via microwires。 Physiological properties of the brain tissue, which may change with disease state, stimulation parameters, which include amplitude and temporal characteristics, and the geometric configuration of the electrode and the surrounding tissue are all parameters on which DBS of both the normal and the diseased brain depend on。 In spite of a huge amount of

studies on DBS, its mechanism of action is still not well understood。 Developing DBS microelectrodes is still challenging。[11]

3、Spinal cord stimulation(SCS)

Spinal cord stimulation (SCS) is an effective therapy for the treatment of chronic and intractable pain including diabetic neuropathy, failed back surgery syndrome, complex regional  pain  syndrome, phantom   limb pain, ischemic   limb pain, refractory   unilateral limb pain syndrome, postherpetic neuralgia and acuteherpes zoster pain。 Another pain condition that is a potential candidate for SCS treatment is Charcot-Marie-Tooth (CMT) disease, which is associated with moderate to severe chronic extremity pain。[12] SCS therapy consists  of  the  electrical  stimulation  of  the  spinal  cord  to   'mask'   pain。   The  gate theory proposed in 1965 by Melzack and Wall[13] provided a theoretical construct to attempt SCS as a clinical treatment for chronic pain。 This theory postulates that activation of large diameter, myelinated primary afferent fibers suppresses the response of dorsal horn neurons to input from small, unmyelinated primary afferents。 A simple SCS system consists of three different parts。 First, microelectrodes are implanted in the epidural space to deliver stimulation pulses to the tissue。 Second, an electrical pulse generator implanted in the lower abdominal area or gluteal region while is connected to the electrodes via wires, and third a remote control to adjust the stimulus parameters such as pulse width and pulse rate in the PG。 Improvements have been made in both the clinical aspects of SCS such as transition from subdural placement of contacts to epidural placement, which reduces the risk and morbidity of SCS implantation, and also technical aspects of SCS such as improving percutaneous leads, and fully implantable multi-channel stimulators。 However, there are many parameters that need to be optimized including number of implanted contacts, contact size and spacing, and electrical sources for stimulation。 The stimulus pulse width and pulse rate are important parameters that need to be adjusted in SCS, which are typically 400 us and 8–200 Hz respectively。[6] rTMS in a rodent。 From Oscar Arias-Carrión, 2008 Transcranial magnetic stimulation(TMS) Main article: Transcranial magnetic stimulation

Compared to electrical stimulation that utilizes brief, high-voltage electric shock to activate neurons, which can potentially activate pain fibers, transcranial magnetic stimulation (TMS) was developed by Baker in 1985。 TMS uses a magnetic wire above the scalp, which carries a sharp and high current pulse。 A time variant magnetic field is induced perpendicular to the coil due to the applied pulse which consequently generates an electric field based on Maxwell's law。 The  electric field provides the necessary current for  a  non-invasive    and