11 This group also compared the effects of stimulating various cortical regions on inhibiting the burst of hyperactivity of thalamic neurons that they associated with neuropathic pain.11 Better long-term inhibition of thalamic firing was induced by stimulating the motor cortex—more specifically, above

the motor cortex site #the site keyword# that corresponds to the painful area. Tsubokawa et al. then implanted electrodes over the motor cortex and longitudinally monitored 11 post-stroke patients with thalamic pain.12 A total of 73% (8/11) reported excellent pain control, which persisted unchanged in five patients (45%) for more than 2 years. Since then, various types of NP have been successfully treated with dural motor cortex stimulation (MCS), including post-stroke pain, spinal cord injury pain, thalamic pain, trigeminal neuralgia, trigeminal Inhibitors,research,lifescience,medical neuropathic pain, and trigeminal deafferentation pain (anesthesia dolorosa) syndromes.13 A recent meta-analysis of the various MCS trials found that 64% of patients with NP reported significant pain relief.14 The fact that up to 70% of these patients would undergo epidural MCS again provides additional evidence of clinical value.15 PRINCIPLES OF NON-INVASIVE

TRANSCRANIAL MAGNETIC STIMULATION (TMS) The success of dural MCS inspired consideration of even less invasive stimulation modalities, and the Inhibitors,research,lifescience,medical best developed currently is transcranial magnetic stimulation (TMS). In TMS, a trained administrator holds an array of electrical coils at a precise location on the patient’s scalp overlying the target cortex. Capacitors are rapidly charged and discharged to pass brief electrical currents through the coils that in turn generate brief strong Inhibitors,research,lifescience,medical magnetic fields. These fields penetrate through nearby tissues, including the scalp, skull, meninges, and cerebrospinal fluid, to induce electric currents in underlying cortical neurons. The frequency of TMS pulses influences the

effects on axons. Low frequencies of less than Inhibitors,research,lifescience,medical 5 Hz will hyperpolarize axons, transiently reducing their normal firing to inhibit their normal effects. This technique can be used Brefeldin_A to map brain functions for experimental reasons or, clinically, to help neurosurgeons identify eloquent areas of cortex to preserve during surgery. It is safer than the Wada test previously used for this purpose, and less dependent on patient cooperation than functional MRI. In contrast, frequencies higher than 5 Hz—and typically 10 Hz is used—serve to depolarize the axolemma, and, if the current is sufficiently strong, this will trigger action potentials in nearby neurons. These then propagate along the axons towards their usual postsynaptic targets. The TMS magnetic fields only reach 2–3 cm into the cortex, and the spatial configuration of the affected area depends on the device properties, coil configuration, and axonal orientation.