***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 
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    Input: OBJECTIVE Several studies have shown that exposure to opioids for short or long periods alters pain sensitivity . Little is known about changes in pain sensitivity during and after tapering of long-term prescribed opioid treatment in chronic low-back pain ( cLBP ) patients . DESIGN The goal of this prospect i ve longitudinal study was to investigate pain sensitivity in a homogeneous patient population ( cLBP patients only ) after tapering of long-term ( 17 months )  opioid use and to monitor the changes in pain sensitivity for 6 months . METHODS Pain sensitivity ( thermal sensation and thermal pain thresholds in low back and nondominant h and ) was measured by quantitative sensory testing ( QST ) at 1 day before ( T1 ) , 3 weeks after ( T2 ) , and 6 months after the start of opioid tapering ( T3 ) in 35 patients with both cLBP and opioid medication ( OP ) , 35 opioid-naïve cLBP patients ( ON ) , and 28 individuals with neither pain nor opioid intake ( HC ) . RESULTS Significant differences in heat pain thresholds were found among the three groups at all three time points ( T1 : P=0.001 , T2 : P=0.015 , T3 : P=0.008 ) , but not between the two patient groups . OP patients showed lower cold pain thresholds at T2 than ON patients and HC . At T3 , the heat pain thresholds of OP patients still remained lower than HC ( P=0.017 ) , while those of ON patients were normalized . CONCLUSIONS Our findings suggest that long-term use of opioids does not reduce pain sensitivity in cLBP patients ; opioid tapering may induce brief hyperalgesia that can be normalized over a longer period Abstract Opioids can elicit unexpected changes in pain sensitivity , known as opioid‐induced hyperalgesia ( OIH ) . The aim of this study was to explore whether OIH exists in patients with chronic pain treated with oral opioids ( OP ) versus non‐opioid ( NOP ) analgesics .  The sensitivity to cold pain and the magnitude of diffuse noxious inhibitory control ( DNIC ) were evaluated in 73 OP and 37 NOP treated patients . Pain threshold , intensity and tolerance in response to the cold pressor ( 1 ° C ) were measured . DNIC was tested by co‐administrating conditioned heat stimulation ( 47 ° C ) to the left forearm and a conditioning stimulation of 12 ° C for 30 s to the right h and . The results showed no differences between the two groups in any of the cold pain measures . In contrast , the magnitude of DNIC was significantly larger in the NOP than in the OP treated patients ( p = 0.003 ) . A gender based analysis showed a significant difference in DNIC between OP and NOP treated men only . However , a mixed model ANOVA demonstrated a significant effect of treatment ( OP versus NOP ) ( F = 5.928 , p = 0.017 ) rather than gender on DNIC . A regression analysis showed that opioid dosage and treatment duration had a significant negative effect on the magnitude of DNIC in OP treated men ( β = −2.175 , p = 0.036 and β = −2.061 , p = 0.047 , respectively ) . In conclusion , oral opioids usage for the treatment of chronic pain does not result in abnormal sensitivity to cold pain , but seems to alter pain modulation . The use of ‘ advanced ’ psychophysics tests such as evaluation of DNIC can help underst and ing the phenomenon of OIH BACKGROUND Opioids are the cornerstone therapy for the treatment of moderate to severe pain . Yet , unconfirmed evidence suggests that chronic exposure to opioids may cause hypersensitivity to pain , a phenomenon known as opioid-induced hyperalgesia ( OIH ) . OBJECTIVES The current preliminary prospect i ve study was aim ed to explore the relationship between experimental OIH and clinical opioid induced analgesia ( OIA ) in a model of experimental OIH in patients with chronic radicular pain using intermediate-term opioid therapy . STUDY DESIGN Prospect i ve evaluation SETTING Interdisciplinary Pain Clinic at a referral Health Care Campus METHODS Thirty patients with chronic neuropathic ( radicular ) pain were assessed prior to and following 4 weeks of an individually titrated dose of oral hydromorphone treatment ( 4 - 20 mg/d ) . The assessment s included an evaluation of experimental OIH by testing for heat pain intensity and cold pain tolerance and an assessment of OIA by completing pain and disability question naires . RESULTS Hydromorphone was found to induce hyperalgesia , as measured by an elevation of phasic heat pain intensity ( P < 0.05 ) . At the same time , hydromorphone caused significant clinical analgesic effects . There was a notable reduction in average daily pain scores ( primary analgesic outcome ) of 26 Visual Analog Scale ( 0 - 100 ) points . A significant negative correlation was found between OIH and all OIA measures ( r = -0.389 , P < 0.05 for the primary analgesic outcome ) . Hydromorphone dosage was positively correlated with OIH ( P < 0.01 , r = 0.467 ) and negatively correlated with OIA parameters ( r = -0.592 , P < 0.01 for the primary analgesia outcome ) . LIMITATIONS The nonr and omized , open-label , prospect i ve evaluation . CONCLUSION A 4-week regimen of open-label hydromorphone therapy results in a dose-dependent OIH , which negatively correlates with its analgesic effect . Future r and omized , controlled , and blinded studies are needed to verify these preliminary results & NA ; Opioid substitution treatment for dependence may alter sensitivity to pain . Previous studies on pain sensitivity in methadone maintenance patients have yielded contradictory results . This study compared nociceptive responses between 16 patients on stable , once daily , doses of methadone and 16 matched control subjects . Two types of nociceptive stimuli were used : ( 1 ) electrical stimulation ; and ( 2 ) a cold pressor test . Two parameters were measured : detection for onset of pain , and pain tolerance .  Methadone patients were tested over an inter‐dosing period : at the time of trough plasma methadone concentration ( 0 h ) , and 3 h after their daily dose . Control subjects were tested twice 3 h apart . Blood sample s were collected to determine plasma methadone concentration . In methadone patients , trough to peak increases in mean R‐(−)‐ and S‐(+)‐methadone concentrations ( 118 and 138 ng/ml to 185 and 259 ng/ml , respectively ) result ed in significant increases in pain detection and tolerance values for both nociceptive stimuli . Using electrical stimulation , methadone patients ' pain tolerance values were lower than controls at 0 h , but higher than controls at 3 h ; no significant differences in pain detection values were found . For the cold pressor test , methadone patients detected pain significantly earlier than controls at 0 h , and were also substantially less pain tolerant than controls at both 0 and 3 h. There were no significant differences in pain detection values between the two groups at 3 h. Pain tolerance to pain detection ratios for methadone patients were significantly lower than controls for the cold pressor test at 0 and 3 h , and for electrical stimulation at 0 h only . In summary , the relative pain sensitivity of methadone maintenance patients is determined by the nature of the nociceptive stimulus ( e.g. cold pressor test versus electrical stimulation ) , the plasma methadone concentration ( trough versus peak plasma concentration ) , and whether thresholds are determined for detection of pain or pain tolerance . Although responding to changes in plasma methadone concentration , maintenance patients are markedly hyperalgesic to pain induced by the cold pressor test BACKGROUND Evidence for opioid-induced hyperalgesia ( OIH ) has been shown in animal and human studies , but the clinical implication s of this phenomenon remain unclear . OBJECTIVES We examined whether cancer patients taking opioids  differ in their sensitivity to a clinical pain stimulus using a local anesthetic injection compared to those not taking opioids . We also evaluated the effect of the opioid dose , duration of opioid therapy , and patients ' pain severity and functional status on this clinical pain stimulus . STUDY DESIGN Prospect i ve observational study . SETTING University outpatient department for interventional pain management , Republic of Korea . METHODS Eighty-two cancer patients including 20 patients not taking opioids ( non-opioid group ) and 62 taking opioids ( opioid group ) who were scheduled for an interventional procedure were enrolled in this study . Patients received a st and ardized subcutaneous injection of lidocaine prior to a full dose of local anesthetic ( LA ) . Before the injection , patients completed the Brief Pain Inventory  ( BPI ) question naire and were asked to rate their current pain using numeric rating scales . Immediately following the injection , LA injection-specific pain was evaluated using pain intensity , unpleasantness , and behavior pain scores . RESULTS LA injection-specific pain intensity , unpleasantness , and behavior pain score were significantly higher in the opioid group compared with the non-opioid group ( P < 0.001 ) . In the opioid group , these post-injection pain scores were higher in patients taking high-dose opioids than those taking low doses ( P < 0.05 ) . In addition , we observed a strong correlation between the baseline BPI pain interference score and the LA injection-specific pain score ( r = 0.695 , P < 0.001 ) . LIMITATIONS This study is limited by its sample size and observational design . Various opioid medications , which were not st and ardized , may have inadvertently biased our results . Finally , the pain assessed by a brief stimulus does not fully reflect disturbances in endogenous pain inhibitory processes . CONCLUSION The results of this study suggest that opioid medication is an important contributing factor to pain perception accompanying LA injection , and cancer patients using high-dose opioids may be highly susceptible to hyperalgesic responses to this clinical stimulus . We also suggest that the possible presence of OIH may be intensified among cancer patients with poor physical and psychosocial functional status UNLABELLED There is accumulating evidence that opioid therapy might not only be associated with the development of tolerance but also with an increased sensitivity to pain , a condition referred to as opioid-induced hyperalgesia ( OIH ) . However , there are no prospect i ve studies documenting the development of opioid tolerance or OIH in patients with chronic pain . This preliminary study in 6 patients with chronic low back pain prospect ively evaluated the development of tolerance and OIH . Patients were assessed before and 1 month after initiating oral morphine therapy . The cold pressor test and experimental heat pain were used to measure pain sensitivity before and during a target-controlled infusion with the short-acting mu opioid agonist remifentanil . In the cold pressor test , all patients became hyperalgesic as well as tolerant after 1 month of oral morphine therapy . In a model of heat pain , patients exhibited no hyperalgesia , although tolerance could not be evaluated . These results provide the first prospect i ve evidence for the development of analgesic tolerance and OIH by using experimental pain in patients with chronic back pain . This study also vali date d methodology for prospect ively study ing these phenomena in larger population s of pain patients . PERSPECTIVE Experimental evidence suggests that opioid tolerance and opioid-induced hyperalgesia might limit the clinical utility of opioids in controlling chronic pain . This study vali date s a pharmacologic approach to study these phenomena prospect ively in chronic pain patients and suggests that both conditions do occur within 1 month of initiating opioid therapy Summary After 1 month of oral morphine therapy , chronic low‐back pain patients developed tolerance but not opioid‐induced hyperalgesia . Improvements in pain and functional ability were observed . Abstract Although often successful in acute setting s , long‐term use of opioid pain medications may be accompanied by waning levels of analgesic response not readily attributable to advancing underlying disease , necessitating dose escalation to attain pain relief . Analgesic tolerance , and more recently opioid‐induced hyperalgesia , have been invoked to explain such declines in opioid effectiveness over time . Because both phenomena result in inadequate analgesia , they are difficult to distinguish in a clinical setting . Patients with otherwise uncomplicated low‐back pain were titrated to comfort or dose‐limiting side effects in a prospect i ve , r and omized , double‐blind , placebo‐controlled clinical trial using sustained‐release morphine or weight‐matched placebo capsules for 1 month . A total of 103 patients completed the study , with an average end titration dose of 78 mg morphine/d . After 1 month , the morphine‐treated patients developed tolerance to the analgesic effects of remifentanil , but did not develop opioid‐induced hyperalgesia . On average , these patients experienced a 42 % reduction in analgesic potency . The morphine‐treated patients experienced clinical ly relevant improvements in pain relief , as shown by a 44 % reduction in average visual analogue scale pain levels and a 31 % improvement in functional ability . The differences in visual analogue scale pain levels ( P = .003 ) and self‐reported disability ( P = .03 ) between both treatment groups were statistically significant . After 1 month of oral morphine therapy , patients with chronic low‐back pain developed tolerance but not opioid‐induced hyperalgesia . Improvements in pain and functional ability were observed OBJECTIVE The purpose of this study was to investigate the associations between morphine equivalent dose and heat pain ( HP ) perception in patients with chronic pain undergoing opioid tapering in the context of a multidiscipl 
    Output:
    
Although none of the stimuli were capable of detecting patients ' hyperalgesia , heat pain sensitivity showed some promising results .