***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Pain is often a complaint that precedes total knee arthroplasty ( TKA ) , however the procedure itself is associated with considerable post-operative pain lasting days to weeks which can predict longer-term surgical outcomes . Previously , we reported significant opioid-sparing effects of motor cortex transcranial direct current stimulation from a single-blind trial . In the present study , we used double-blind methodology to compare motor cortex tDCS and prefrontal cortex tDCS to both sham and active-control ( active electrodes over non-pain modulating brain areas ) tDCS . METHODS 58 patients undergoing unilateral TKA were r and omly assigned to receive 4 20-min sessions ( a total of 80 min ) of tDCS ( 2 mA ) post-surgery with electrodes placed to create 4 groups : 1 ) MOTOR ( n = 14 ) ; anode-motor/cathode-right prefrontal , 2 ) PREFRONTAL ( n = 16 ) ; anode-left-prefrontal/cathode-right-sensory , 3 ) ACTIVE-CONTROL ( n = 15 ) ; anode-left-temporal-occipital junction/cathode-medial-anterior-premotor-area , and 4 ) SHAM ( n = 13 ) ; 0 mA-current stimulation using placements 1 or 2 .  Patient controlled analgesia ( PCA ; hydromorphone )  use was tracked during the ∼72-h post-surgery . RESULTS Patients in the sham group and the active-control group used 15.4 mg ( SD = 14.1 ) and 16.0 mg ( SD = 9.7 ) of PCA hydromorphone respectively . There was no difference between the slopes of the cumulative PCA usage curves between these two groups ( p = 0.25 ; ns ) . Patients in the prefrontal tDCS group used an average of 11.7 mg ( SD = 5.0 ) of PCA hydromporhone , and the slope of the cumulative PCA usage curve was significantly lower than sham ( p < 0.0001 ) . However , patients in the motor tDCS group used an average of 19.6 mg ( SD = 11.9 ) hydromorphone and the slope of the PCA use curve was significantly higher than sham ( p < 0.0001 ) . CONCLUSIONS Results from this double-blind cortical-target-optimization study suggest that anodal transcranial direct current stimulation ( tDCS ) over the left prefrontal cortex may be a reasonable approach to reducing post-TKA opioid requirements . Given the unexpected finding that motor cortex failed to produce an opioid sparing effect in this follow-up trial , further research in the area of post-operative cortical stimulation is still needed Transcranial direct current stimulation ( tDCS ) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation . Anodal tDCS enhances and cathodal stimulation reduces excitability . Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation , while cathodal tDCS hyperpolarises cortical neurones . However , not much is known about the ion channels and receptors involved in these effects . Thus , the impact of the sodium channel blocker carbamazepine , the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested . tDCS- protocol s inducing excitability alterations ( 1 ) only during tDCS and ( 2 ) eliciting long-lasting after-effects were applied after drug administration . Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS . Flunarizine result ed in similar changes . Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation , which elicits no after-effects , but prevented the induction of long-lasting after-effects independent of their direction . These results suggest that , like in other animals , cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation , thus modulating the conductance of sodium and calcium channels . Moreover , they suggest that the after-effects may be NMDA receptor dependent . Since NMDA receptors are involved in neuroplastic changes , the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting . The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS , which may have important future clinical applications The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body , by means of surgically-implanted epidural electrodes is a vali date d therapeutical strategy to control medication-resistant neurogenic pain . Repetitive transcranial magnetic stimulation ( rTMS ) permits to stimulate non-invasively and precisely the motor cortex . We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a ' real ' or a ' sham ' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy . We studied the effects of rTMS on pain level assessed on a 0 - 10 visual analogue scale from day 1 to day 12 following the rTMS session . A significant pain decrease was observed up to 8 days after the ' real ' rTMS session . This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex Background Transcranial direct current stimulation ( tDCS ) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing . Methods Ten patients with classical trigeminal neuralgia ( TN ) were stimulated daily for 20 minutes over two weeks using anodal ( 1 mA ) or sham tDCS over the primary motor cortex ( M1 ) in a r and omized double-blind cross-over design . Primary outcome variable was pain intensity on a verbal rating scale ( VRS 0–10 ) . VRS and attack frequency were assessed for one month before , during and after tDCS . The impact on trigeminal pain processing was assessed with pain-related evoked potentials ( PREP ) and the nociceptive blink reflex ( nBR ) following electrical stimulation on both sides of the forehead before and after tDCS . Results Anodal tDCS  reduced pain intensity significantly after two weeks of treatment . The attack frequency reduction was not significant . PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS . No severe adverse events were reported . Conclusion Anodal tDCS over two weeks ameliorates intensity of pain in TN . It may become a valuable treatment option for patients unresponsive to conventional treatment Repetitive transcranial magnetic stimulation ( rTMS ) delivered at various intensities and frequencies excites cortical motor areas . Trains of stimuli ( at 5 Hz frequency , and suprathreshold intensity ) progressively increase the size of muscle evoked potentials ( MEPs ) and the duration of the cortical silent period ( CSP ) in normal subjects . The aim of this study was to evaluate the effect of the antiepileptic drugs carbamazepine , gabapentin , and topiramate on cortical excitability variables tested with rTMS . We tested the changes in motor threshold , MEP size and CSP duration evoked by focal rTMS in 23 patients with neuropathic pain before and after a 1-week course of treatment with carbamazepine , gabapentin , topiramate and placebo .  None of the three antiepileptic drugs changed the resting or active magnetic and electrical motor threshold .  Antiepileptic treatment , but not placebo , abolished the normal rTMS-induced facilitation of MEPs , but left the progressive lengthening of the CSP during the rTMS train unchanged . Our results suggest that carbamazepine , gabapentin and topiramate modulate intracortical excitability by acting selectively on excitatory interneurons Weak transcranial direct current stimulation ( tDCS ) induces persisting excitability changes in the human motor cortex . These plastic excitability changes are selectively controlled by the polarity , duration and current strength of stimulation . To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity , we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine ( CBZ ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan ( DMO ) . Monitored by transcranial magnetic stimulation ( TMS ) , motor cortical excitability changes of up to 40 % were achieved in the drug-free condition . Increase of cortical excitability could be selected by anodal stimulation , and decrease by cathodal stimulation . Both types of excitability change lasted several minutes after cessation of current stimulation . DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation , strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity . In contrast , CBZ selectively eliminated anodal effects . Since CBZ stabilizes the membrane potential voltage-dependently , the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials . Similar to the induction of established types of short- or long-term neuroplasticity , a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS . On the basis of these results , we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects , leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex . This study was design ed to assess the influence of pain origin , pain site , and sensory loss on rTMS efficacy . Patients and methods : Sixty right h and ed patients were included , suffering from intractable pain secondary to one of the following types of lesion : thalamic stroke , brainstem stroke , spinal cord lesion , brachial plexus lesion , or trigeminal nerve lesion . The pain predominated unilaterally in the face , the upper limb , or the lower limb . The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated . Finally , the pain level was scored on a visual analogue scale before and after a 20 minute session of " real " or " sham " 10 Hz rTMS over the side of the motor cortex corresponding to the h and on the painful side , even if the pain was not experienced in the h and itself . Results and discussion : The percentage pain reduction was significantly greater following real than sham rTMS ( −22.9 % v −7.8 % , p = 0.0002 ) , confirming that motor cortex rTMS was able to induce antalgic effects . These effects were significantly influenced by the origin and the site of pain . For pain origin , results were worse in patients with brainstem stroke , whatever the site of pain . This was consistent with a descending modulation within the brainstem , triggered by the motor corticothalamic output . For pain site , better results were obtained for facial pain , although stimulation was targeted on the h and cortical area . Thus , in contrast to implanted stimulation , the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one . Across representation plasticity of cortical areas result ing from deafferentation could explain this discrepancy . Finally , the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects . Conclusion : Motor cortex rTMS was found to result in a significant but transient relief of chronic pain , influenced by pain origin and pain site . These parameters should be taken into account in any further study of rTMS application in chronic pain control It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 & NA ; The double‐blinded r and omized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events . & NA ; There is little evidence for multisession repetitive transcranial magnetic stimulation ( rTMS ) on pain relief in patients with neuropathic pain ( NP ) , although single‐session rTMS was suggested to provide transient pain relief in NP patients . We aim ed to assess the efficacy and safety of 1 
    Output:
    
Significant pain reductions were obtained in both techniques .
More number of sessions yielded to more durable effects .
Conclusion TMS and tDCS appear to be safe and promising alternatives to reduce pain intensity in different chronic OFP disorders .