***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: In the voluntary contractions , output force can be maintained constant although the inhibitory influences exerted by pain on muscle activity . We investigated changes in the spontaneous and evoked activity of the abductor digiti minimi muscle ( ADM ) and the biceps brachii muscle ( BIC ) in healthy volunteers during constant force noxious contraction  , result ing from chemically activated nociceptive afferents .  EMG-force relationship , motor-evoked response ( MEP ) to  transcranial magnetic stimulation and determinism ( DET ) of surface EMG signals during constant force contraction was analyzed before , during and after chemically induced tonic activation of their nociceptive afferents . Under constant force contraction , amplitude of surface EMG signal decreased in BIC and increased in ADM during pain with respect to control condition . In both muscles , the size of motor-evoked potential ( MEP ) induced by  transcranial magnetic stimulation ( TMS ) of the primary motor cortex was significantly higher during pain than in control . Level of determinism extracted from surface EMG signal by non-linear method was similarly and significantly increased in both muscles during pain stimulation . Finally , nociceptive stimulation caused a decline in steadiness of the force exerted by ADM and BIC . These results are interpreted in terms of increased corticospinal synchronizing inputs . The possibility that it may play a role in governing force production to counteract pain inhibitory influences on motor system is considered The human cerebral processing of noxious input from skin and muscle was compared with the use of positron emission tomography with intravenous H2(15)O to detect changes in regional cerebral blood flow ( rCBF ) as an indicator of neuronal activity . During each of eight scans , 11 normal subjects rated the intensity of stimuli delivered to the nondominant ( left ) forearm on a scale ranging from 0 to 100 with 70 as pain threshold . Cutaneous pain was produced with a high-energy CO2 laser stimulator . Muscle pain was elicited with high-intensity intramuscular electrical stimulation . The mean ratings of perceived intensity for innocuous and noxious stimulation were 32.6 + /- 4.5 ( SE ) and 78.4 + /- 1.7 for cutaneous stimulation and 15.4 + /- 4.2 and 73.5 + /- 1.4 for intramuscular stimulation . The pain intensity ratings and the differences between noxious and innocuous ratings were similar for cutaneous and intramuscular stimuli ( P > 0.05 ) . After stereotactic registration , statistical pixel-by-pixel summation ( Z score ) and volumes-of-interest ( VOI ) analyses of subtraction images were performed . Significant increases in rCBF to both noxious cutaneous and intramuscular stimulation were found in the contralateral secondary somatosensory cortex ( SII ) and inferior parietal lobule [ Brodmann area ( BA ) 40 ] . Comparable levels of rCBF increase were found in the contralateral anterior insular cortex , thalamus , and ipsilateral cerebellum . Noxious cutaneous stimulation caused significant activation in the contralateral lateral prefrontal cortex ( BA 10/46 ) and ipsilateral premotor cortex ( BA 4/6 ) . Noxious intramuscular stimulation evoked rCBF increases in the contralateral anterior cingulate cortex ( BA 24 ) and subsignificant responses in the contralateral primary sensorimotor cortex ( MI/SI ) and lenticular nucleus . These activated cerebral structures may represent those recruited early in nociceptive processing because both forms of stimuli were near pain threshold . Correlation analyses showed a negative relationship between changes in rCBF for thalamus and MI/SI for cutaneous stimulation , and positive relationships between thalamus and anterior insula for both stimulus modalities . Direct statistical comparisons between innocuous cutaneous and intramuscular stimulation with the use of Z scores and VOI analyses showed no reliable differences between these two forms of noxious stimulation , indicating a substantial overlap in brain activation pattern . The comparison of noxious cutaneous and intramuscular stimulation indicated more activation in the premotor cortex , SII , and prefrontal cortex with cutaneous stimulation , but these differences did not reach statistical significance . The similar cerebral activation patterns suggest that the perceived differences between acute skin and muscle pain are mediated by differences in the intensity and temporospatial pattern of neuronal activity within similar sets of forebrain structures Although pathological muscle pain involves a significantly larger population than any other pain condition , the central mechanisms are less explored than those of cutaneous pain . The aims of the study were to establish the pain matrix for muscle pain in the full head volume and , further , to explore the possibility of a functional segregation to nonpainful and painful stimuli within the area of the parasylvian cortex corresponding to the secondary somatosensory area . Additionally , we speculate that a r and omization of nonpainful and painful stimuli may target specific structures related to stimulus salience . We used event-related functional magnetic resonance imaging ( MRI ) and the high sensitivity of the 3-T MRI scanner to study the central processing of acute muscle pain induced by intramuscular electrostimulation . Brief nonpainful and painful stimuli ( 1-ms duration , interstimulus interval = 12 s ) were r and omly applied to the left abductor pollicis brevis of 10 subjects . The data disclose a pain matrix for muscle pain similar to that for cutaneous pain . Individual analysis suggests separate representations within the area bounded by the upper bank of the Sylvian fissure ( SF ) and the circular sulcus of insula ( CSI ) . Nonpainful stimulation activated the superficial parietal operculum adjoining the SF , while the painful condition additionally targeted the deeper parietal operculum bordering the CSI . R and omization of stimuli of different intensities likely introduces cognitive components that engage neural substrates servicing the appreciation of stimulus salience in the context of affect-laden pain imposition Abstract All pain is unpleasant , but different perceptual and emotional qualities are characteristic of pain originating in different structures . Pain of superficial ( cutaneous ) origin usually is sharp and restricted , whereas pain of deep origin ( muscle/viscera ) generally is dull and diffuse . Despite the differences it has been suggested previously that all pain is mediated by an invariant set ( ‘ neuromatrix ’ ) of brain structures . However , we report here , using functional magnetic resonance imaging ( fMRI ) , that striking regional differences in brain activation patterns were the rule . Signal differences were found in regions implicated in emotion ( perigenual cingulate cortex ) , stimulus localization and intensity ( somatosensory cortex ) and motor control ( motor cortex , cingulate motor area ) . Further , most fMRI signal changes matched perceived changes in pain intensity . These findings clearly indicate that distinct neural activity patterns in distinct sets of brain structures are evoked by pain originating from different tissues of the body . Further , we suggest that these differences underlie the different perceptual and emotional reactions evoked by deep versus superficial pain OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Training is a mainstay in the clinical management of neck pain , yet , effects of various training protocol s are only small to moderate and improvements are required . Previous investigations of the nervous system indicate a correlation between neuroplastic adaptation to training and functional recovery . The interaction between neck pain and training thus needs further exploration . This was a r and omized experimental study of the effects of experimental neck pain and training on corticomotor excitability . Healthy volunteers were r and omized to  training and experimental neck pain , training and no pain , and pain and no training . Primary endpoints were corticomotor excitability assessed by transcranial magnetic stimulation and electromyography measured as changes in amplitudes and latencies of motor evoked potentials ( MEPs ) , recorded at baseline and after 30 min , 1 h , and 1 week . Additionally , correlations between changes in MEPs and motor learning , effects of pain and concomitant neck training on pain , muscle strength , and fatigue were investigated . Data were analyzed by repeated measurement ANOVA , paired t tests , Grubbs ' outlier test and correlation coefficients . Results indicated that neck pain and training significantly enhanced the inhibition of the amplitudes of the MEPs for 1 week . The results indicate that moderate neck pain and training induce long-lasting inhibition of the corticomotor pathways . This inhibition may limit the outcome of neck training in painful conditions in contrast to pain-free training conditions Earlier investigations have shown that stimulation of peripheral afferent nerves induces prolonged changes in the excitability of the human motor cortex . The present study compared the effect of experimental pain and non-painful conditioning stimulation on motor evoked potentials ( MEPs ) elicited by transcranial magnetic stimulation ( TMS ) in the relaxed first dorsal interosseous ( FDI ) and flexor carpi ulnaris ( FCU ) muscles . The MEPs were measured in 10 healthy subjects , and stimulus-response curves were generated before and after each of four stimulation paradigms conducted in r and om order on separate occasions : ( a ) control ; ( b ) " dual stimulation " consisting of electrical stimulation of the FDI motor point paired with TMS ; ( c ) painful infusion of hypertonic saline in the FDI muscle ; and ( d ) pain combined with dual stimulation . There were no significant changes in FDI MEPs following the control paradigm , and dual stimulation induced an increase in the FDI MEPs only inconsistently . In contrast , the painful stimulation and the combined pain and dual stimulation paradigms were followed by significant suppression of the FDI MEPs at higher stimulus intensities . No changes were observed in the FCU MEPs following the four paradigms . In two additional subjects , the responses evoked in FDI by direct stimulation of the descending corticospinal tracts were significantly depressed following painful stimulation of the FDI , although the ulnar-evoked M-waves remained constant . It is concluded that muscle pain is followed by a period with profound depression of MEPs amplitudes in the resting muscle , but that these changes are at least in part due to a lasting depression of the excitability of the motoneurones in the spinal cord . Hence , painful stimulation differs from non-painful , repetitive stimulation , which facilitates the corticomotor pathway UNLABELLED Excitability of the motor cortex can be suppressed during muscle pain . Yet the mechanisms are largely unknown . Short interval intracortical inhibition ( SICI ) and intracortical facilitation ( ICF ) were examined as possible c and i date mechanisms to underpin this change . SICI and ICF were investigated in 11 healthy individuals before , during and after infusion of hypertonic saline into right first dorsal interosseous ( FDI ) . Using paired-pulse transcranial magnetic stimulation ( TMS ) , interstimulus intervals of 2 , 3 , and 13 ms were investigated . Pain intensity and quality were recorded using a 10-cm visual analogue scale and the McGill Pain Question naire . Resting motor threshold and motor-evoked potentials ( MEPs ) to single TMS stimuli were recorded before and after pain . Electromyographic recordings were made from right FDI and abductor digiti minimi . Participants reported an average pain intensity of 5.8 ( 1.6 ) cm . MEP amplitudes decreased in both muscles . Compared with the pre-pain condition , SICI was increased following pain , but not during . ICF was decreased both during and after pain when compared with the pre-pain condition . These findings suggest that muscle pain differentially modulates SICI and ICF . Although the functional relevance is unknown , we hypothesize decreased facilitation and increased inhibition may contribute to the restriction of movement of a painful body part . PERSPECTIVE This article provides evidence for decreased intracortical facilitation and increased short interval intracortical inhibition in response to muscle pain . This finding is 
    Output:
    
Meta-analyses of TMS and EEG data revealed moderate to strong evidence of reduced S1 and corticomotor excitability during and following the resolution of muscle pain .
Overall , the findings of this review indicate reduced S1 and corticomotor activity during and after resolution of acute muscle pain , mechanisms that could plausibly underpin altered sensorimotor function in pain .
Through meta-analyses we evaluate the strength of evidence concerning the direction and temporal profile of the S1/M1 response to acute muscle pain