***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: & NA ; ‘ Diffuse noxious inhibitory controls ’ ( DNIC ) , a form of supraspinal descending endogenous analgesia , requires a noxious conditioning stimulus for pain attenuation . This may be partly dependent on a distraction effect . The term “ conditioned pain modulation ” ( CPM ) has recently been introduced to describe the psychophysical paradigm to test DNIC . The present study aim ed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation . Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers . For conditioning , the right h and was immersed in 46.5 ° C water . Distraction was provided by three different difficulty levels of continuous cognitive visual tasks . Experimental blocks consisted of test pain : ( 1 ) alone ; ‘ baseline ’ , ( 2 ) with conditioning pain ; ‘ CPM ’ , ( 3 ) with distraction ; ‘ distraction ’ and ( 4 ) with conditioning pain and distraction ; ‘ combined ’ . They were r and omized and repeated three times and pain intensity and unpleasantness rated . Results showed an overall effect of experimental block on test pain intensity ( P = 0.0125 ) . Post‐hoc tests revealed a significant reduction in pain intensity ratings under Combined ( 21.2 ± 2.3 ; mean ± SEM ) compared to CPM alone ( 16.0 ± 2.3 ) ( P < 0.05 ) . Furthermore , at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM . Based on the additive effect of CPM and distraction  on pain inhibition , and the cases of no distraction despite CPM , we suggest that CPM acts independently from distraction The aim of this study was to evaluate the function of pain modulating systems subserving diffuse noxious inhibitory controls ( DNICs ) in primary headaches . DNICs were examined in 24 migraineurs , 17 patients with chronic tension-type headache ( CTTH ) and 20 healthy subjects by means of nociceptive flexion RIII reflex and the cold pressor test ( CPT ) as heterotopic noxious conditioning stimulation ( HNCS ) . The subjective pain thresholds ( Tp ) and the RIII reflex threshold ( Tr ) were significantly lower in CTTH vs. controls . In controls a significant inhibition of the RIII reflex was observed during the CPT ( -30± , P < 0.05 ) . Conversely , migraine and CTTH patients  showed facilitation ( + 31± , P < 0.05 and + 40± , P < 0.01 , respectively ) of the RIII reflex during the HNCS . This study demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH . Impairment of endogenous supraspinal pain modulation systems may contribute to the development and /or maintenance of central sensitization in primary headaches UNLABELLED Pain catastrophizing is among the most robust predictors of pain outcomes , and a disruption in endogenous pain-inhibitory systems is 1 potential mechanism that may account for increased pain among individuals who report higher pain catastrophizing . Pain catastrophizing may negatively influence diffuse noxious inhibitory controls ( DNIC ) , a measure of endogenous pain inhibition , through complex anatomical circuitry linking cortical responses to pain with processes that modulate pain . The current study examined whether DNIC mediated the relationship between catastrophizing and pain among 35 healthy young adults and examined the moderating effects of sex to determine whether the magnitude or direction of associations differed among men and women .  DNIC was assessed using pressure pain thresholds on the forearm before and during a cold pressor task . Using bias-corrected bootstrapped confidence intervals , results showed that diminished DNIC was a significant partial mediator of the relation between greater pain-related catastrophizing and more severe pain ratings . Participant sex moderated these associations ; higher catastrophizing predicted lower DNIC for men and women , however , the effect of catastrophizing on pain ratings was partially mediated by DNIC for women only . These findings further support the primary role of pain catastrophizing in modulation of pain outcomes . PERSPECTIVE These findings support the hypothesis that the heightened pain reported by individuals higher in pain catastrophizing may be related to a disruption in the endogenous modulation of pain , operationalized by assessing DNIC . Whether interventions that reduce pain catastrophizing affect pain outcomes via effects on DNIC is in need of investigation ABSTRACT In 10 patients with central post‐stroke pain ( CPSP ) , the influence of ischemia‐induced heterotopic noxious conditioning stimulation ( HNCS ) on the intensity of spontaneous ongoing‐ and brush‐evoked pain was examined . In addition , the modulating effect of ongoing pain and HNCS on pain sensitivity in a remote pain‐free area was explored . A semi‐quantitative brushing technique was employed in combination with a computerized  visual analogue scale ( VAS ) to monitor the allodynic percept over time , by calculating the area under the VAS curve as the total brush‐evoked pain intensity . Heat‐ and pressure pain thresholds and sensitivity to suprathreshold heat‐ and pressure pain in the pain‐free area were assessed before and during HNCS . No significant alterations of ongoing‐ or brush‐evoked pain were found during HNCS , although 6 of 10 patients rated a reduction of about 50 % of the brush‐evoked pain . At baseline significantly increased pressure pain sensitivity ( threshold P < 0.05 ; suprathreshold P = 0.05 ) were demonstrated in patients compared to controls . During HNCS , higher pressure pain thresholds were demonstrated in patients and controls alike ( P < 0.001 ) , whereas in controls only decreased sensitivity to suprathreshold pressure pain was found ( P < 0.05 ) . Lack of influence from HNCS on ongoing‐ and brush‐evoked pain on a group level , indicates inability of modulation from endogenous pain controlling systems on nociceptive activity generated in the brain . Increased pressure pain sensitivity at baseline suggests alteration in corticofugal control of nociceptive sensitivity due to the brain lesion , whereas patients during HNCS seemed to activate modulatory systems interacting with nociceptive input from the spinal level equal to controls & NA ; Visceral pain processing is abnormal in a majority of irritable bowel syndrome ( IBS ) patients . Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study . Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following r and omised stimuli : sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation . Heterotopic stimulation  decreased rectal pain scores from 3.7 ± 0.2 to 3.1 ± 0.3 ( mean ± SE , scale 0–5 ) in controls ( p < 0.01 ) , but not significantly in IBS . Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula , SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation . Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS . Rectal pain scores were similarly low during sham stimulation in both groups , but brain activation patterns differed . In conclusion , IBS patients  showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration . Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive , homeostatic , associative and emotional areas , even though pain scores were similar during sham distension . The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself Impaired central pain modulation is implicated in the pathophysiology of chronic pain . In this controlled experiment , we evaluated whether partial sleep loss altered endogenous pain inhibition and reports of spontaneous pain .  Thirty-two healthy females were studied polysomnographically for 7 nights . On Nights 1 - 2 ( Baseline ) , subjects slept undisturbed for 8 hours . After Night 2 , subjects were r and omized to Control ( N = 12 ) , Forced Awakening ( FA , N = 10 ) , or Restricted Sleep Opportunity ( RSO , N = 10 ) conditions . Controls continued to sleep undisturbed . FA underwent 8 forced awakenings ( one per hour ) on Nights 3 - 5 . RSO subjects were yoked to FA on total sleep time ( TST ) , receiving partial sleep deprivation by delayed bedtime . On Night 6 , both FA & RSO underwent 36 hours total sleep deprivation ( TSD ) , followed by 11-hour recovery sleep ( Night 7 ) . Subjects completed twice-daily psychophysical assessment s of mechanical pain thresholds and pain inhibition ( Diffuse Noxious Inhibitory Controls ) , via use of a conditioning stimulus ( i.e. , cold pressor ) paradigm . FA and RSO demonstrated 50 % reductions in total sleep time and increases in nonpainful somatic symptoms during partial sleep deprivation . While sleep deprivation had no effect on pain thresholds , during partial sleep deprivation the FA group demonstrated a significant loss of pain inhibition and an increase in spontaneous pain ; neither of the other 2 groups showed changes in pain inhibition or spontaneous pain during partial sleep deprivation . These data suggest that sleep continuity disturbance , but not simple sleep restriction , impairs endogenous pain-inhibitory function and increases spontaneous pain , supporting a possible pathophysiologic role of sleep disturbance in chronic pain UNLABELLED Persistent shoulder pain is a common complication after stroke . Its etiology and underlying mechanisms are not well understood and treatment is generally unsatisfactory . The objective of this study was to assess the role of central sensitization and disinhibition in chronic stroke patients with chronic PSSP ( n = 19 ) , pain-free stroke patients ( n = 29 ) , and healthy controls ( n = 23 ) .  Positive and negative somatosensory symptoms and signs were assessed using clinical examination and electrical and mechanical quantitative sensory testing ( QST ) . Conditioned pain modulation ( CPM )  was assessed by comparing QST thresholds before and after applying a cold pressor test .  Sensory abnormalities were more frequently observed and more severe in patients with PSSP , including positive signs such as allodynia at the affected side and generalized hyperalgesia at the unaffected side . CPM was similar in stroke patients and healthy controls . This study showed that chronic PSSP was associated with several positive and negative somatosensory signs , implicating a role for central sensitization and possibly for disinhibition . Since the causal relationship remains unclear , and may be related to either neuroplasticity induced by ongoing nociception as well as to the neuropathic brain lesion , prospect i ve studies are warranted . PERSPECTIVE The assessment of somatosensory symptoms and signs and endogenous pain modulation demonstrated a role for central sensitization and possibly for disinhibition in chronic PSSP . Prevention and treatment of PSSP could benefit from a more detailed analysis of both peripheral and central pain mechanisms OBJECTIVE To examine possible deficiencies in endogenous pain modulating mechanisms in fibromyalgia patients compared with matched pain-free control subjects . DESIGN /SUBJECTS/ METHODOLOGY : Pain reduction was investigated in 25 female patients with fibromyalgia and 26 age-matched healthy women using the diffuse noxious inhibitory controls ( DNIC ) paradigm . Tonic thermal stimuli at painful and nonpainful intensities , tailored to individual heat pain thresholds , were employed to induce pain inhibition . The anticipated effect was assessed by measuring the electrical pain threshold and detection threshold , using a double staircase method . Only nontender control points were stimulated ( thermode on the foot , electrodes on the inner forearm ) . RESULTS The patients with fibromyalgia had significantly lower heat pain thresholds than the healthy subjects , but similar electrical detection and pain thresholds . The repeatedly applied electrical stimuli result ed in a degree of perceptual adaptation that was similar between the two groups . However , concurrent tonic thermal stimuli , at both painful and nonpainful levels , significantly increased the electrical pain threshold in the healthy subjects but not in the fibromyalgia patients . The electrical detection threshold was not affected in either group . CONCLUSIONS Pain modulation , produced by a concurrent tonic stimulus in healthy persons , was not seen in the fibromyalgia group . The patients either had deficient pain modulation or were unable to tolerate a tonic stimulus intense enough to engage a modulatory process . It remains to be established whether the pain reduction found in the healthy subjects was the conventional DNIC effect , another effect ( e.g. , distraction ) , or a combination of both This double-blind , within-subjects experiment examined the effect of ingesting a large dose of caffeine on perceptions of leg muscle pain during moderate intensity cycling exercise . Low-caffeine-consuming college-aged males ( n = 16 ) ingested either caffeine ( 10 mg x kg(-1 ) body weight ) or placebo and 1 hour later completed 30 minutes of moderate intensity cycling exercise ( 60 % VO(2peak ) ) . The order of drug administration was counter-balanced . Perceptions of leg muscle pain as well as work rate , heart rate , and oxygen uptake ( VO(2 ) ) were recorded during exercise . Leg muscle pain ratings were significantly and moderately reduced after a high dose of caffeine . This observation suggests that prior reports showing caffeine improves endurance exercise performance might be partially explained by caffeine 's hypoal 
    Output:
    
Analysis of moderator variables indicated a significant influence of participant gender and age on the effect size .
It is concluded that  conditioned pain modulation  is impaired in population s with chronic pain .
PERSPECTIVE This review compared the efficacy of  conditioned pain modulation  between chronic pain and healthy population s. The finding of impaired modulation in the chronic pain groups highlights the dysfunction of endogenous pain modulatory mechanisms in this population