***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 30 human subjects , experimental pain was produced by either ischemia or cold-water immersion . In a double-blind procedure , intravenous doses of up to 10 milligrams of naloxone hydrochloride in saline were indistinguishable from similarly administered saline alone . There were no effects on subjective pain ratings , finger plethysmograph recordings , or responses to mood-state question naires . These laboratory procedures do not activate any functionally significant pain-attenuating or mood-altering effect of endorphins The analgesic effects of the synthetic opiate fentanyl citrate ( 0.1 mg ) on subjective pain reports ( SPR ) and late-wave event-related potentials ( ERP ) recorded during painful dental stimulation were examined in human subjects . Such waves have been shown to reflect the contribution of cognitive variables , such as expectancy and belief , to perception . In addition , the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone ( 1.2 or 0.4 mg ) or normal saline ( double-blind ) following IV fentanyl administration . Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents , such as nitrous oxide , acupuncture , and aspirin . Naloxone injection reversed both ERP and SPR changes , but surprisingly , a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection . By change , all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology , and so placebo reversal was hypothesized . Alternatively , it was hypothesized that fentanyl cleared more rapidly than predicted , thus , producing apparent reversal . In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals , subjects received 0.1 mg fentanyl , but no reversal injection . The  fentanyl effect was constant across this time period . The data , thus support the hypothesis that the saline-induced reversal seen in experiment 1 , where the subjects were knowledgeable in opiate pharmacology , was placebo opiate antagonism & NA ; Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in underst and ing the mechanisms underlying placebo response . In the present study , we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain . First , we found that part of the placebo response was reversed by naloxone , confirming previous studies on the role of opioids in the placebo phenomenon . Second , since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide , we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia . The placebo effect can thus be modulated in two opposite directions : it can be partially abolished by naloxone and potentiated by proglumide . The fact that placebo potentiation  by proglumide occurred only in placebo responders , but not in non‐responders , suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide . These results suggest an inhibitory role for cholecystokinin in placebo response , although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms 
    Output:
    
Due to their sophisticated design s , these studies probably provide the best evidence that placebo analgesia exists .
They also indicate that placebo analgesia is mediated by endogenous opiates .