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F146 NEURAL MECHANISMS MEDIATING EFFECTS OF EXPECTATION ON VISCERAL PLACEBO ANALGESIA: AN fMRI STUDY IN HEALTHY PLACEBO RESPONDERS AND NON-RESPONDERS
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POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: 36 patients (60) were female and 24 (40%). Opioids were implicated in the treatment of 52 patients (86.8%). BFI was lower in opioid naive patients (19.32 vs 30.64, p = 0.94). There were not statistically differences between the different opioids with oxycodone-naloxone; but BFI was lower (22.09). Laxative therapies were more in opioid treated patients (40.8% vs 16.7%, p < 0.05), and the disagreement with the treatment was higher in opioid naive patients (33.4 vs 21.6%, p = 0.33). Conclusions: • Opioid naive patients obtain lower BFI score. • In the opioid patients, the BFI score was lower in oxycodonenaloxone. • Laxative use is higher in opioid treated patients. • Despite constipation, patients with opioids have higher satisfaction scores. Disclosure: None declared
F145 EFFECT OF LEVORPHANOL, A MULTIMODAL OPIOID AND NONOPIOID ANALGESIC IN THE HOTPLATE ASSAY OF NOCICEPTION N. Babul *, A.K. Rehni, H.D. Kao, Y.S. Chang. Drug Development, Cinergen, LLC, Blue Bell, PA, USA Background and Aims: To evaluate the antinociceptive effects of levorphanol in the rat hotplate assay. Methods: Fifty rats randomly received encoded doses of subcutaneous levorphanol tartrate 0.25, 0.5, 1 and 2 mg/kg or vehicle control. Animals were placed on a hotplate at 53°C and the withdrawal latency (HPWL) recorded at baseline, 30, 45 and 60 min. The percent maximum possible effect (%MPE) was computed, doseresponse curves generated and A50 (50% MPE dose) calculated. Results: Compared to control, levorphanol 0.25 mg/kg resulted in an insignificant increase in HPWL; 0.5 mg/kg increased HPWL at 30 and 45 min post-dose (6.9±0.6s vs. 3.8±0.3 s, P < 0.01; 6.9±0.5 s vs. 4.4±0.3 s, P < 0.05, respectively); 1 mg/kg increased HPWL at 30, 45 and 60 min (7.2±0.5 s vs. 3.8±0.3 s; 8.8±0.7 s vs. 4.4±0.3 s; 7.3±0.7 s vs. 4.3±0.3 s, all P < 0.01, respectively). At 2 mg/kg, the highest tested dose of levorphanol, HPWL increased at 30, 45 and 60 min (9.8±0.9s vs. 3.8±0.3 s; 12.1±0.7 s vs. 4.4±0.3 s; 11.8±0.8 s vs. 4.3±0.3 s, all P < 0.01, respectively). The A50 for levorphanol tartrate was >2.0 mg/kg, 1.5 mg/kg and 1.6 mg/kg at 30, 45 and 60 min. Conclusions: Levorphanol demonstrated time and dose-dependent antinociception in the hot plate assay. Based on available A50 data from subcutaneous HPWL, levorphanol appears to be approximately 5 times more potent than morphine in the hotplate analgesic assay. Disclosure: All authors are scientists eligible for compensation from Cinergen, LLC.
F146 NEURAL MECHANISMS MEDIATING EFFECTS OF EXPECTATION ON VISCERAL PLACEBO ANALGESIA: AN fMRI STUDY IN HEALTHY PLACEBO RESPONDERS AND NON-RESPONDERS S. Elsenbruch1 *, V. Kotsis1 , S. Benson1 , C. Rosenberger2 , D. Reidick1 , M. Schedlowski1 , U. Bingel3 , N. Theysohn4 , E.R. Gizewski5 . 1 Inst. of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, Essen, 2 Inst. of Medical Psychology, 3 Neuroimage Nord, Dept. of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, 4 Inst. of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, 5 Dept. of Neuroradiology, Centre for Radiology, University Clinic of Gieben and Marburg, Giessen, Germany Background and Aims: Understanding the mechanisms of placebo analgesia in the context of visceral pain is important given evidence of clinical benefit of placebo treatment in irritable bowel syndrome. This functional magnetic resonance imaging (fMRI) study analyzed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects.
Methods: In N = 36 subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing participants’ expectations regarding the probability of receiving an analgesic drug to 0, 50 and 100%. Placebo responders were identified by median split based on pain reduction (0–100%). Results: Expectation of pain relief resulted in overall reductions in pain, and this response was significantly more pronounced in responders. FMRI analyses within responders revealed that pain reductions correlated with altered activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex and thalamus during anticipation (paired t-tests on the contrast 0>100%); during pain, the placebo response correlated with thalamus activation. Compared to non-responders, responders demonstrated significantly greater placebo-induced changes in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex and thalamus during pain. Conclusions: The expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of abdominal pain in IBS. Disclosure: None declared
F147 CLASSICALLY CONDITIONED NOCEBO EFFECTS ON HEAT-PAIN PERCEPTION WITHOUT VERBAL SUGGESTION 1 A.-K. Brascher ¨ *, S. Becker2 , D. Kleinbohl ¨ 1 , R. Holzl ¨ 1 . 1 Otto Selz Institute, University of Mannheim, Mannheim, Germany; 2 Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada Background and Aims: Pain perception is subject to modulation due to various factors, among others placebo and nocebo effects. Expectation (induced e.g. by verbal suggestion) and conditioning are suggested to cause placebo/nocebo effects but it is still unclear if conditioning alone alters perceptual processes. Therefore, this study (N = 21) explores the role of conditioning in altered heat-pain perception. Other than most studies, this study investigates effects of conditioning on behavior measures in addition to subjective ratings. Thereby different components of the response can be separated and effects of mere response bias ruled out. Methods: Different thermal stimuli (32 and 36°C) contingently preceded a non-painful and painful heat stimulus in order to induce classical conditioning. After a conditioning phase, both stimuli were followed by the non-painful temperature. Results: Successful conditioning (nocebo effect) of perception of the non-painful temperature was present in 13 out of 21 participants (responders). However, the non-painful temperature was perceived as hotter but not as painful with successful conditioning. While subjective ratings were increased in the responders, behavioral measures indicated enhanced habituation to the non-painful temperature. Successful conditioning was independent of contingency awareness. Conclusions: Classical conditioning resulted in a nocebo effect, i.e. increased subjective heat perception. In contrast, behavioral responses showed increased perceptual habituation. Thus, subjective and behavioral responses to conditioning of perceptual processes dissociated with opposing direction of perceptual change. Possibly, the aversiveness of the painful stimulus was too low to induce conditioning in all participants and to generate a nocebo effect in the painful range (hyperalgesia). Disclosure: None declared
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
Results: 36 patients (60) were female and 24 (40%). Opioids were implicated in the treatment of 52 patients (86.8%). BFI was lower in opioid naive patients (19.32 vs 30.64, p = 0.94). There were not statistically differences between the different opioids with oxycodone-naloxone; but BFI was lower (22.09). Laxative therapies were more in opioid treated patients (40.8% vs 16.7%, p < 0.05), and the disagreement with the treatment was higher in opioid naive patients (33.4 vs 21.6%, p = 0.33). Conclusions: • Opioid naive patients obtain lower BFI score. • In the opioid patients, the BFI score was lower in oxycodonenaloxone. • Laxative use is higher in opioid treated patients. • Despite constipation, patients with opioids have higher satisfaction scores. Disclosure: None declared
F145 EFFECT OF LEVORPHANOL, A MULTIMODAL OPIOID AND NONOPIOID ANALGESIC IN THE HOTPLATE ASSAY OF NOCICEPTION N. Babul *, A.K. Rehni, H.D. Kao, Y.S. Chang. Drug Development, Cinergen, LLC, Blue Bell, PA, USA Background and Aims: To evaluate the antinociceptive effects of levorphanol in the rat hotplate assay. Methods: Fifty rats randomly received encoded doses of subcutaneous levorphanol tartrate 0.25, 0.5, 1 and 2 mg/kg or vehicle control. Animals were placed on a hotplate at 53°C and the withdrawal latency (HPWL) recorded at baseline, 30, 45 and 60 min. The percent maximum possible effect (%MPE) was computed, doseresponse curves generated and A50 (50% MPE dose) calculated. Results: Compared to control, levorphanol 0.25 mg/kg resulted in an insignificant increase in HPWL; 0.5 mg/kg increased HPWL at 30 and 45 min post-dose (6.9±0.6s vs. 3.8±0.3 s, P < 0.01; 6.9±0.5 s vs. 4.4±0.3 s, P < 0.05, respectively); 1 mg/kg increased HPWL at 30, 45 and 60 min (7.2±0.5 s vs. 3.8±0.3 s; 8.8±0.7 s vs. 4.4±0.3 s; 7.3±0.7 s vs. 4.3±0.3 s, all P < 0.01, respectively). At 2 mg/kg, the highest tested dose of levorphanol, HPWL increased at 30, 45 and 60 min (9.8±0.9s vs. 3.8±0.3 s; 12.1±0.7 s vs. 4.4±0.3 s; 11.8±0.8 s vs. 4.3±0.3 s, all P < 0.01, respectively). The A50 for levorphanol tartrate was >2.0 mg/kg, 1.5 mg/kg and 1.6 mg/kg at 30, 45 and 60 min. Conclusions: Levorphanol demonstrated time and dose-dependent antinociception in the hot plate assay. Based on available A50 data from subcutaneous HPWL, levorphanol appears to be approximately 5 times more potent than morphine in the hotplate analgesic assay. Disclosure: All authors are scientists eligible for compensation from Cinergen, LLC.
F146 NEURAL MECHANISMS MEDIATING EFFECTS OF EXPECTATION ON VISCERAL PLACEBO ANALGESIA: AN fMRI STUDY IN HEALTHY PLACEBO RESPONDERS AND NON-RESPONDERS S. Elsenbruch1 *, V. Kotsis1 , S. Benson1 , C. Rosenberger2 , D. Reidick1 , M. Schedlowski1 , U. Bingel3 , N. Theysohn4 , E.R. Gizewski5 . 1 Inst. of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, Essen, 2 Inst. of Medical Psychology, 3 Neuroimage Nord, Dept. of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, 4 Inst. of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, 5 Dept. of Neuroradiology, Centre for Radiology, University Clinic of Gieben and Marburg, Giessen, Germany Background and Aims: Understanding the mechanisms of placebo analgesia in the context of visceral pain is important given evidence of clinical benefit of placebo treatment in irritable bowel syndrome. This functional magnetic resonance imaging (fMRI) study analyzed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects.
Methods: In N = 36 subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing participants’ expectations regarding the probability of receiving an analgesic drug to 0, 50 and 100%. Placebo responders were identified by median split based on pain reduction (0–100%). Results: Expectation of pain relief resulted in overall reductions in pain, and this response was significantly more pronounced in responders. FMRI analyses within responders revealed that pain reductions correlated with altered activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex and thalamus during anticipation (paired t-tests on the contrast 0>100%); during pain, the placebo response correlated with thalamus activation. Compared to non-responders, responders demonstrated significantly greater placebo-induced changes in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex and thalamus during pain. Conclusions: The expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of abdominal pain in IBS. Disclosure: None declared
F147 CLASSICALLY CONDITIONED NOCEBO EFFECTS ON HEAT-PAIN PERCEPTION WITHOUT VERBAL SUGGESTION 1 A.-K. Brascher ¨ *, S. Becker2 , D. Kleinbohl ¨ 1 , R. Holzl ¨ 1 . 1 Otto Selz Institute, University of Mannheim, Mannheim, Germany; 2 Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada Background and Aims: Pain perception is subject to modulation due to various factors, among others placebo and nocebo effects. Expectation (induced e.g. by verbal suggestion) and conditioning are suggested to cause placebo/nocebo effects but it is still unclear if conditioning alone alters perceptual processes. Therefore, this study (N = 21) explores the role of conditioning in altered heat-pain perception. Other than most studies, this study investigates effects of conditioning on behavior measures in addition to subjective ratings. Thereby different components of the response can be separated and effects of mere response bias ruled out. Methods: Different thermal stimuli (32 and 36°C) contingently preceded a non-painful and painful heat stimulus in order to induce classical conditioning. After a conditioning phase, both stimuli were followed by the non-painful temperature. Results: Successful conditioning (nocebo effect) of perception of the non-painful temperature was present in 13 out of 21 participants (responders). However, the non-painful temperature was perceived as hotter but not as painful with successful conditioning. While subjective ratings were increased in the responders, behavioral measures indicated enhanced habituation to the non-painful temperature. Successful conditioning was independent of contingency awareness. Conclusions: Classical conditioning resulted in a nocebo effect, i.e. increased subjective heat perception. In contrast, behavioral responses showed increased perceptual habituation. Thus, subjective and behavioral responses to conditioning of perceptual processes dissociated with opposing direction of perceptual change. Possibly, the aversiveness of the painful stimulus was too low to induce conditioning in all participants and to generate a nocebo effect in the painful range (hyperalgesia). Disclosure: None declared