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F173 REPRODUCIBILITY OF HUMAN EXPERIMENTAL SURROGATE MODELS
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POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
on pressure pain tolerance 0.45 (0.0512), CPM on electric pain 0.53 (0.021). Conclusions: Most QST were reliable. In this preliminary analysis, low reliability of some tests may partly be due to lack of statistical power. Disclosure: None declared
F173 REPRODUCIBILITY OF HUMAN EXPERIMENTAL SURROGATE MODELS I.M. Larsen1 *, T. Andresen1 , B. Koch-Henriksen1 , D. Lassen1 , A.K. Nielsen1 , A.M. Drewes1 , L. Arendt-Nielsen2 . 1 Mech-Sense, Department of Gastroenterology, Aalborg Hospital, 2 Center for Sensory-Motore Interaction (SMI), Aalborg University, Aalborg, Denmark Background and Aims: Ongoing pain, allodynia and hyperalgesia are prominent symptoms in chronic pain conditions. To investigate these symptoms experimental surrogate models can be used e.g. intradermal injection of capsaicin, glutamate or nerve growth factor (NGF). The aim of this study was to investigate reproducibility of these models. Methods: Twenty healthy male volunteers (mean age 25.3±4.4 years, range 18–38 years) participated in two separated studies, each consisting of two identical periods: 1. intradermal injection of glutamate and capsaicin separated by minimum 7 days and 2. intradermal injection of NGF separated by minimum 21 days. Allodynia was assessed with brush and hyperalgesia was measured with von Frey filaments (26 g and 60 g). Sensitivity to heat and pressure in the NGF injection area was determined. Results: Study 1: There were no significant differences in the areas assessed between days (allodynia: Glutamate: P = 0.3; Capsaicin: P = 1.0; hyperalgesia: Glutamate: P > 0.5; Capsaicin: P > 0.5). Study 2: There were no significant differences in allodynia neither 1 h (P = 0.2) or 24 h (P = 0.6) after NGF injection. This was also the case for hyperalgesia (1 h: P > 0.3; 24h: P > 0.5). All volunteers were sensitised to heat (P < 0.001) as well as to pressure (P = 0.008) 24 h after NGF injection. In both studies areas assessed with the two sizes of von Frey filaments (26 g and 60 g) showed no significant differences (P > 0.5). All ICC were >0.77. Conclusions: The models were reproducible between days and are applicable in basic as well as in clinical studies investigating analgesic effects and mechanisms. Disclosure: None declared
F174 TOPICAL HIGH-CONCENTRATION MENTHOL – REPRODUCIBILITY OF A HUMAN SURROGATE MODEL OF NEUROPATHIC PAIN F. Mahn *, P. Hullemann, ¨ G. Wasner, R. Baron, A. Binder. Department of Neurology, Division of Neurological Pain Research and Therapy, Christian-Albrechts-Universit¨ at Kiel, Kiel, Germany Background and Aims: The reproducibility of human pain models is a prerequisite for proof-of-concept trials which use pharmacological treatments. The aim of this study was to investigate the reproducibility of the topical high-concentration menthol pain model in human volunteers. Recent studies have shown that in this model cold and mechanical hyperalgesia can be studied. Methods: In 10 healthy volunteers high-concentration (40%) menthol was applied to both ventral forearms twice daily, four hours apart, in a randomised order. The identical procedure was repeated 1 week later. Before and after application quantitative sensory testing (QST; DFNS protocol) was performed in the application area. T-test was used to investigate differences before and after menthol application and the agreement between the two application days. Pearson correlation was used to demonstrate
correlation coefficients. P values <0.05 were regarded as statistical significant. Results: The application of 40% menthol led to a significantly reduced cold pain (CPT) and increased mechanical pain sensitivity (MPS), indicating cold and mechanical pin-prick hyperalgesia (p < 0.001 resp.). Correlation analysis revealed high correlation coefficients [r = 0.96/0.89 (CPT); 0.87/0.93 (MPS)] and no significant differences (t-test; p = 0.21–0.74). Conclusions: The menthol pain model is highly reproducible within the period of 1 week and therefore suitable for the investigation of menthol-evoked sensory symptoms and signs (cold hyperalgesia; mechanical pin-prick hyperalgesia), e.g. with pharmacological interventions. Acknowlegments: This study is a part of the Europain project, funded by the Innovative Medicines Initiative Joint Undertaking (IMI JU; www.imi.europa.eu) Grant no 115007 and an unrestricted financial grant from Pfizer Germany. Disclosure: None declared
F175 ROLE OF NEGATIVE AND POSITIVE EMOTIONS IN SENSITIVITY TO PAIN AND ITCH A. van Laarhoven1 , A. Walker1 , O. Wilder-Smith1 , S. Kroeze2 , P. van Riel1 , P. van de Kerkhof1 , F. Kraaimaat1 , A. Evers1 *. 1 Radboud University Nijmegen Medical Centre, 2 Radboud University Nijmegen, Nijmegen, The Netherlands Background and Aims: Emotions play an important role in pain responses. Experimental studies have shown that negative emotions can enhance the intensity of perceived pain or reduce tolerance to pain when compared to positive emotions. To date, little is known about the effects of emotions on the sensitivity to itch. The present study was directed to compare the effects of negative and positive emotions on the sensitivity to pain and itch. Methods: Film fragments were used to induce a negative and positive emotional state in healthy female subjects. Pain and itch were induced using the following somatosensory stimuli: electrical stimulation, histamine iontophoresis, and the cold pressor test. Electrical and cold pressor tolerance thresholds were determined as well as levels of pain and itch evoked by the stimuli. Results: Results indicate that emotions can influence not only physical symptoms of pain, but also itch sensations. Conclusions: The findings that emotional state may lead to a heightened sensitivity of itch and other physical symptoms has important consequences for understanding the aetiology and maintenance of sensitization mechanisms, suggesting a vicious circle in which chronic symptoms of pain and itch lead to increased negative emotions and in turn increase physical sensations. Disclosure: None declared
F176 FACIAL INJECTIONS OF PRURITOGENS OR ALGOGENS ELICIT DISTINCT BEHAVIOR RESPONSES AND EXCITE OVERLAPPING POPULATIONS OF PRIMARY AND SECOND-ORDER TRIGEMINAL NEURONS E. Carstens *, A.H. Klein, M. Iodi Carstens. Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA Background and Aims: We investigated if intradermal (id) cheek injection of pruritogens or algogens differentially elicits hindlimb scratches or forelimb wipes in rats, and if they activate separate or overlapping populations of primary sensory trigeminal ganglion (TG) and dorsal root ganglion (DRG) cells, and second-order neurons in trigeminal subnucleus caudalis (Vc). Methods: Behavioral studies counted numbers of hindlimb scratch bouts, and ipsilateral forelimb wipes, directed to site of cheek microinjection of pruritogens or algogens. We used calcium imaging of cultured TG and DRG cells, and single-unit recordings from
POSTER SESSIONS / European Journal of Pain Supplements 5 (2011) 15–295
on pressure pain tolerance 0.45 (0.0512), CPM on electric pain 0.53 (0.021). Conclusions: Most QST were reliable. In this preliminary analysis, low reliability of some tests may partly be due to lack of statistical power. Disclosure: None declared
F173 REPRODUCIBILITY OF HUMAN EXPERIMENTAL SURROGATE MODELS I.M. Larsen1 *, T. Andresen1 , B. Koch-Henriksen1 , D. Lassen1 , A.K. Nielsen1 , A.M. Drewes1 , L. Arendt-Nielsen2 . 1 Mech-Sense, Department of Gastroenterology, Aalborg Hospital, 2 Center for Sensory-Motore Interaction (SMI), Aalborg University, Aalborg, Denmark Background and Aims: Ongoing pain, allodynia and hyperalgesia are prominent symptoms in chronic pain conditions. To investigate these symptoms experimental surrogate models can be used e.g. intradermal injection of capsaicin, glutamate or nerve growth factor (NGF). The aim of this study was to investigate reproducibility of these models. Methods: Twenty healthy male volunteers (mean age 25.3±4.4 years, range 18–38 years) participated in two separated studies, each consisting of two identical periods: 1. intradermal injection of glutamate and capsaicin separated by minimum 7 days and 2. intradermal injection of NGF separated by minimum 21 days. Allodynia was assessed with brush and hyperalgesia was measured with von Frey filaments (26 g and 60 g). Sensitivity to heat and pressure in the NGF injection area was determined. Results: Study 1: There were no significant differences in the areas assessed between days (allodynia: Glutamate: P = 0.3; Capsaicin: P = 1.0; hyperalgesia: Glutamate: P > 0.5; Capsaicin: P > 0.5). Study 2: There were no significant differences in allodynia neither 1 h (P = 0.2) or 24 h (P = 0.6) after NGF injection. This was also the case for hyperalgesia (1 h: P > 0.3; 24h: P > 0.5). All volunteers were sensitised to heat (P < 0.001) as well as to pressure (P = 0.008) 24 h after NGF injection. In both studies areas assessed with the two sizes of von Frey filaments (26 g and 60 g) showed no significant differences (P > 0.5). All ICC were >0.77. Conclusions: The models were reproducible between days and are applicable in basic as well as in clinical studies investigating analgesic effects and mechanisms. Disclosure: None declared
F174 TOPICAL HIGH-CONCENTRATION MENTHOL – REPRODUCIBILITY OF A HUMAN SURROGATE MODEL OF NEUROPATHIC PAIN F. Mahn *, P. Hullemann, ¨ G. Wasner, R. Baron, A. Binder. Department of Neurology, Division of Neurological Pain Research and Therapy, Christian-Albrechts-Universit¨ at Kiel, Kiel, Germany Background and Aims: The reproducibility of human pain models is a prerequisite for proof-of-concept trials which use pharmacological treatments. The aim of this study was to investigate the reproducibility of the topical high-concentration menthol pain model in human volunteers. Recent studies have shown that in this model cold and mechanical hyperalgesia can be studied. Methods: In 10 healthy volunteers high-concentration (40%) menthol was applied to both ventral forearms twice daily, four hours apart, in a randomised order. The identical procedure was repeated 1 week later. Before and after application quantitative sensory testing (QST; DFNS protocol) was performed in the application area. T-test was used to investigate differences before and after menthol application and the agreement between the two application days. Pearson correlation was used to demonstrate
correlation coefficients. P values <0.05 were regarded as statistical significant. Results: The application of 40% menthol led to a significantly reduced cold pain (CPT) and increased mechanical pain sensitivity (MPS), indicating cold and mechanical pin-prick hyperalgesia (p < 0.001 resp.). Correlation analysis revealed high correlation coefficients [r = 0.96/0.89 (CPT); 0.87/0.93 (MPS)] and no significant differences (t-test; p = 0.21–0.74). Conclusions: The menthol pain model is highly reproducible within the period of 1 week and therefore suitable for the investigation of menthol-evoked sensory symptoms and signs (cold hyperalgesia; mechanical pin-prick hyperalgesia), e.g. with pharmacological interventions. Acknowlegments: This study is a part of the Europain project, funded by the Innovative Medicines Initiative Joint Undertaking (IMI JU; www.imi.europa.eu) Grant no 115007 and an unrestricted financial grant from Pfizer Germany. Disclosure: None declared
F175 ROLE OF NEGATIVE AND POSITIVE EMOTIONS IN SENSITIVITY TO PAIN AND ITCH A. van Laarhoven1 , A. Walker1 , O. Wilder-Smith1 , S. Kroeze2 , P. van Riel1 , P. van de Kerkhof1 , F. Kraaimaat1 , A. Evers1 *. 1 Radboud University Nijmegen Medical Centre, 2 Radboud University Nijmegen, Nijmegen, The Netherlands Background and Aims: Emotions play an important role in pain responses. Experimental studies have shown that negative emotions can enhance the intensity of perceived pain or reduce tolerance to pain when compared to positive emotions. To date, little is known about the effects of emotions on the sensitivity to itch. The present study was directed to compare the effects of negative and positive emotions on the sensitivity to pain and itch. Methods: Film fragments were used to induce a negative and positive emotional state in healthy female subjects. Pain and itch were induced using the following somatosensory stimuli: electrical stimulation, histamine iontophoresis, and the cold pressor test. Electrical and cold pressor tolerance thresholds were determined as well as levels of pain and itch evoked by the stimuli. Results: Results indicate that emotions can influence not only physical symptoms of pain, but also itch sensations. Conclusions: The findings that emotional state may lead to a heightened sensitivity of itch and other physical symptoms has important consequences for understanding the aetiology and maintenance of sensitization mechanisms, suggesting a vicious circle in which chronic symptoms of pain and itch lead to increased negative emotions and in turn increase physical sensations. Disclosure: None declared
F176 FACIAL INJECTIONS OF PRURITOGENS OR ALGOGENS ELICIT DISTINCT BEHAVIOR RESPONSES AND EXCITE OVERLAPPING POPULATIONS OF PRIMARY AND SECOND-ORDER TRIGEMINAL NEURONS E. Carstens *, A.H. Klein, M. Iodi Carstens. Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA Background and Aims: We investigated if intradermal (id) cheek injection of pruritogens or algogens differentially elicits hindlimb scratches or forelimb wipes in rats, and if they activate separate or overlapping populations of primary sensory trigeminal ganglion (TG) and dorsal root ganglion (DRG) cells, and second-order neurons in trigeminal subnucleus caudalis (Vc). Methods: Behavioral studies counted numbers of hindlimb scratch bouts, and ipsilateral forelimb wipes, directed to site of cheek microinjection of pruritogens or algogens. We used calcium imaging of cultured TG and DRG cells, and single-unit recordings from