38,41,42 Most studies had small sample sizes, with only four recruiting more than 40 Epigenetic inhibitor libraries patients (mean = 25, median = 20). Another limitation is the variation in applied stimulation parameters such as frequency (ranged from 5 Hz to 20 Hz), intensity of RMT (ranged from 80% to 115%), and total number of pulses (ranged between 120 and 2,500). A 2010 Cochrane Systematic Review concluded that higher stimulation frequencies (>5 Hz), greater numbers of stimuli (>500), and multiple sessions (>1) yielded better Inhibitors,research,lifescience,medical results.45

The contribution of many TMS factors, including coil orientation, duration of each pulse train, inter-train interval, and number of trains, is not yet understood. An additional unresolved question concerns which site within the motor cortex yields the strongest benefit for pain patients. Most studies stimulated the motor cortical representation of patients’ painful site, but one suggested that stimulating adjacent Inhibitors,research,lifescience,medical motor cortex sites yields better analgesia.24 Placebo effects also need to be better addressed. These are considerable in both pain trials and device trials. However, given that TMS evokes both visual, auditory, and tactile sensations, sham procedures are difficult to design, and there is no consensus regarding the best design of a true Inhibitors,research,lifescience,medical double-blinded, sham-controlled study, since researchers and often subjects can usually distinguish between real and sham devices.45 Some methods of sham TMS offer

visual verisimilitude, Inhibitors,research,lifescience,medical e.g. inert or inactivated TMS coils, but fail to produce auditory and electrical sensations. SAFETY CONCERNS PERTAINING TO MOTORCORTEX rTMS TREATMENT OF NP Although the big advantages of TMS are its non-invasiveness and lack of extracranial effects, there are safety Inhibitors,research,lifescience,medical considerations, particularly when many TMS pulses are applied repeatedly, as required for clinical effects. Detailed safety guidelines established at a 2009 global consensus conference of experts establish absolute and relative contraindications to TMS.46 Like MRI, TMS is absolutely contraindicated for people with ferromagnetic

implants in or near the head, including shrapnel or medical implants, because magnetic fields might cause the metal to move or overheat. Magnetic pulses can also cause electronically controlled devices to malfunction or fail. In patients without intracranial ferromagnetic implants, the only potentially serious complication of TMS is the possibility of inducing Rutecarpine a single seizure. This is an expected consequence of triggering action potentials in cortical neurons. Therefore, TMS is relatively contraindicated and, in most cases, should not be administered to patients with increased seizure risk, for instance those with epilepsy or epileptogenic brain lesions (e.g. strokes or tumors), or taking medications that increase seizure risk (some antibiotics, antivirals, antidepressants and other psychiatric medications, illicit drugs, and alcohol).