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290 IS THERE MORE TO PAIN RELIEF THAN A REDUCTION IN PAIN INTENSITY? A PSYCHOPHYSICAL INVESTIGATION
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European Journal of Pain 2006, Vol 10 (suppl S1)
Conclusion: Excellent data reproducibility within subjects has validated this model. This model may mimic many of those features characteristics of neuropathic pain and could be utilised as a future biomarker in pain research. 290 Accepted for oral presentation IS THERE MORE TO PAIN RELIEF THAN A REDUCTION IN PAIN INTENSITY? A PSYCHOPHYSICAL INVESTIGATION S. Leknes1,2 ° , K. Wiech1,2 , J. Brooks1,2 , I. Tracey1,2 . 1 Dept. Physiology, Anatomy & Genetics, University of Oxford, 2 Oxford Centre for Functional Magnetic Resonance Imaging, University of Oxford, Oxford, UK Pain relief is often defined simply as a reduction in pain intensity. However, a connection between pain relief and reward processing has been proposed. Homeostatic theories predict that relief intensity and pleasantness depends on the extent of the deviation from homeostatic balance and the efficacy of the restoration to homeostasis. To test these predictions, we devised a simple VAS scale with anchors “No relief ” and “Most relief imaginable”. Study 1 employed brief noxious thermal stimulation to investigate pain and relief timings when rated in real-time. Study 2 used the capsaicin (0.075%) model for heat hyperalgesia and skin cooling to examine the effect of relief efficacy. Following noxious heat stimuli, skin temperature was alternately returned to baseline (35ºC) or cooled to 25ºC. Relief pleasantness ratings were also obtained. In study 3, we examined the relationship between pain reduction and relief by parametrically varying the intensity of brief noxious heat stimuli. In all studies, subjects reported feeling pain relief at the offset of each heat stimulus. Study 1 showed that relief onset followed immediately after the pain sensation peaked. When sensitised skin was cooled below the baseline in study 2, relief ratings increased significantly (mean intensity change 3.7±0.3, mean pleasantness change 2.7±1.2, 11-point scales). This effect is consistent with the efficacy of cooling in restoring ideal skin temperature after a burn. Results from study 3 showed a linear correlation between relief and pain intensity, again supporting predictions that pain relief depends on the extent and efficacy of the recovery towards homeostasis.
291 SPREAD AND REFERRAL OF EXPERIMENTAL PAIN DURING DIFFERENT JAW TASKS Sae-Lee ° ,
D. T. Whittle, C.C. Peck, G.M. Murray. Jaw Function and Orofacial Pain Research Unit, Westmead Centre for Oral Health/Westmead Hospital, Westmead, NSW, Australia Background and Aims: We examined whether the spread and referral of experimental jaw muscle pain varied with the jaw task performed. Methods: 22 pain-free subjects participated in a within-subject design. University of Sydney Ethics Committee approved the study. Experimental pain was elicited in the right masseter (bolus infusion of 4.5% hypertonic saline: 0.2 ml over 20 s, and tonic infusion: 6−9 ml/h for ~20 min). Pain intensity and location was monitored on a 100-mm visual analogue scale (VAS) and pain map. Isotonic saline was infused as a non-algesic control. During baseline, pain (hypertonic), and isotonic conditions, subjects performed 3−5 trials each of standardized protrusion, contralateral, open/close, chewing (tracking a target) and non-standardized clenching. VAS and pain maps were obtained after each jaw task trial. Results: Hypertonic saline produced persistent moderate pain (30−60 mm on VAS). Most subjects (n = 15) reported discrete pain at the injection site and localized within the boundary of the masseter and this was similar from task to task. Some subjects (n = 7) pain areas including ipsilateral TMJ, mandibular, orbital, submandibular, temporal or intraoral regions. This spread of pain could vary within and between jaw tasks e.g., referred temple pain likely occurred during jaw opening, chewing and clenching rather than protrusion and contralateral movements (n = 4). Conclusions: Localized experimental pain distribution was unlikely to be affected by different jaw tasks. However, individual variability of pain distribution did occur and this may be partly jaw-task dependent. Supported by the NHMRC, IPRS of Australia, and ADRF, Inc.
Abstracts, 5th EFIC Congress, Free Presentations 292 REPRODUCIBILITY AND VARIABILITY OF THE HUMAN EXPERIMENTAL PAIN MODEL OF CONTINUOUS CUTANEOUS ELECTRICAL STIMULATION M. Segerdahl1 ° , M. Carlsson1 , B. H¨aggl¨of2 , N. Sj¨ogren3 , B. Jonzon4 , M. Schmelz5 , A. Sollevi1 . 1 Department for Clinical Science, Intervention and Technology, CLINTEC, Unit for Anesthesia, Karolinska University Hospital Huddinge, Stockholm, 2 Clinical Pharmacology, AstraZeneca R&D S¨odert¨alje, 3 Biostatistics, AstraZeneca R&D S¨odert¨alje, 4 Discovery Medicine, AstraZeneca R&D S¨odert¨alje, Norway, 5 Department of Anesthesiology and Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany Background and Aims: The methodological characteristics of human pain models used to predict efficacy of analgesics are critical, yet insufficiently documented. We have investigated the reproducibility and variability of a recently introduced model of evoked pain and hyperalgesia in human skin using continuous cutaneous electrical stimulation (CCES). Methods: High current density electrical stimulation (2Hz, 20−80 mA for 100 min using two electrodes in microdialysis fibers applied in parallel intracutaneously) was used to induce pain (numeric rating scale 6), axon reflex flare (Laser-Doppler), and areas of hyperalgesia and allodynia in 24 healthy subjects (14 male, 10 female aged 21−41 years) on four consecutive test sessions, one week apart. Results: CCES evoked reproducible pain and areas of hyperalgesia and allodynia with no significant difference or trend over time. Variability was lower within-subjects than between-subjects. The coefficients of variance (CV%) were 14 and 17, 37 and 48, and 59 and 67 for pain, hyperalgesia and allodynia respectively. Sex, previous experience of pain models or placement of electrodes did not influence the outcome. Power calculation revealed that 6 and 16 subjects respectively would be required to get a statistical power of 80%, to detect a 30% decrease in pain score and hyperalgesia in a cross-over design at significance level 5%. The method was well tolerated. Conclusions: CCES is a stable and reproducible method to evoke ongoing pain, hyperalgesia and allodynia. By choosing a crossover design, the model can detect efficacy of analgesics in a limited number of healthy subjects.
293 PAIN THRESHOLD AND STRESS-INDUCED ANALGESIA IN ANOREXIA NERVOSA AND HEALTHY WOMEN: THE ROLE OF STEROID HORMONES A. Yamamotova1 ° , H. Papezova2 , V. Kmoch2 . 1 Department of Normal, Pathological and Clinical Physiology, Charles University, 3rd Faculty of Medicine, Prague, 2 Department of Psychiatry, Charles University, 1st Faculty of Medicine, Prague, Czech Republic In healthy women, sensitivity to pain depends on levels of gonadal hormones. As estrogens have a pain-modulation effect, we assume that decreased levels of sex steroids contribute to weakened nociception in anorexia nervosa (AN). The aim of present study was to analyze association between adrenocortical and gonadal steroid hormones and thermal nociception in healthy women and in AN patients treated with hormonal substitution therapy. The pain threshold latencies on radiant heat stimuli were measured under rest and stress (mental arithmetic task) conditions in 20 DSM-IV diagnosed anorexia patients and in 21 healthy women. Blood samples were collected in a routine way in the morning hours and were taken for laboratory analyses of the plasma levels of estradiol, 17-OH progesterone, DHEA, DHEA-S and cortisol. AN patients taking HRT did not differ by any hormonal levels from controls. The pain threshold was significantly higher only in patients with the level of estradiol lower than 0.08 nmol/l. In both groups, the rest pain threshold negatively correlated with DHEA-S (r = −0.42, p = 0.008). The magnitude of stressinduced analgesia during mental arithmetic did not differ between groups and was estradiol independent. However, analgesia correlated positively in both groups with DHEA (r = 0.4974, p = 0.001), in anorexia with DHEA-S (r = 0.4833, p = 0.036) and in healthy women with 17-OH progesterone
European Journal of Pain 2006, Vol 10 (suppl S1)
Conclusion: Excellent data reproducibility within subjects has validated this model. This model may mimic many of those features characteristics of neuropathic pain and could be utilised as a future biomarker in pain research. 290 Accepted for oral presentation IS THERE MORE TO PAIN RELIEF THAN A REDUCTION IN PAIN INTENSITY? A PSYCHOPHYSICAL INVESTIGATION S. Leknes1,2 ° , K. Wiech1,2 , J. Brooks1,2 , I. Tracey1,2 . 1 Dept. Physiology, Anatomy & Genetics, University of Oxford, 2 Oxford Centre for Functional Magnetic Resonance Imaging, University of Oxford, Oxford, UK Pain relief is often defined simply as a reduction in pain intensity. However, a connection between pain relief and reward processing has been proposed. Homeostatic theories predict that relief intensity and pleasantness depends on the extent of the deviation from homeostatic balance and the efficacy of the restoration to homeostasis. To test these predictions, we devised a simple VAS scale with anchors “No relief ” and “Most relief imaginable”. Study 1 employed brief noxious thermal stimulation to investigate pain and relief timings when rated in real-time. Study 2 used the capsaicin (0.075%) model for heat hyperalgesia and skin cooling to examine the effect of relief efficacy. Following noxious heat stimuli, skin temperature was alternately returned to baseline (35ºC) or cooled to 25ºC. Relief pleasantness ratings were also obtained. In study 3, we examined the relationship between pain reduction and relief by parametrically varying the intensity of brief noxious heat stimuli. In all studies, subjects reported feeling pain relief at the offset of each heat stimulus. Study 1 showed that relief onset followed immediately after the pain sensation peaked. When sensitised skin was cooled below the baseline in study 2, relief ratings increased significantly (mean intensity change 3.7±0.3, mean pleasantness change 2.7±1.2, 11-point scales). This effect is consistent with the efficacy of cooling in restoring ideal skin temperature after a burn. Results from study 3 showed a linear correlation between relief and pain intensity, again supporting predictions that pain relief depends on the extent and efficacy of the recovery towards homeostasis.
291 SPREAD AND REFERRAL OF EXPERIMENTAL PAIN DURING DIFFERENT JAW TASKS Sae-Lee ° ,
D. T. Whittle, C.C. Peck, G.M. Murray. Jaw Function and Orofacial Pain Research Unit, Westmead Centre for Oral Health/Westmead Hospital, Westmead, NSW, Australia Background and Aims: We examined whether the spread and referral of experimental jaw muscle pain varied with the jaw task performed. Methods: 22 pain-free subjects participated in a within-subject design. University of Sydney Ethics Committee approved the study. Experimental pain was elicited in the right masseter (bolus infusion of 4.5% hypertonic saline: 0.2 ml over 20 s, and tonic infusion: 6−9 ml/h for ~20 min). Pain intensity and location was monitored on a 100-mm visual analogue scale (VAS) and pain map. Isotonic saline was infused as a non-algesic control. During baseline, pain (hypertonic), and isotonic conditions, subjects performed 3−5 trials each of standardized protrusion, contralateral, open/close, chewing (tracking a target) and non-standardized clenching. VAS and pain maps were obtained after each jaw task trial. Results: Hypertonic saline produced persistent moderate pain (30−60 mm on VAS). Most subjects (n = 15) reported discrete pain at the injection site and localized within the boundary of the masseter and this was similar from task to task. Some subjects (n = 7) pain areas including ipsilateral TMJ, mandibular, orbital, submandibular, temporal or intraoral regions. This spread of pain could vary within and between jaw tasks e.g., referred temple pain likely occurred during jaw opening, chewing and clenching rather than protrusion and contralateral movements (n = 4). Conclusions: Localized experimental pain distribution was unlikely to be affected by different jaw tasks. However, individual variability of pain distribution did occur and this may be partly jaw-task dependent. Supported by the NHMRC, IPRS of Australia, and ADRF, Inc.
Abstracts, 5th EFIC Congress, Free Presentations 292 REPRODUCIBILITY AND VARIABILITY OF THE HUMAN EXPERIMENTAL PAIN MODEL OF CONTINUOUS CUTANEOUS ELECTRICAL STIMULATION M. Segerdahl1 ° , M. Carlsson1 , B. H¨aggl¨of2 , N. Sj¨ogren3 , B. Jonzon4 , M. Schmelz5 , A. Sollevi1 . 1 Department for Clinical Science, Intervention and Technology, CLINTEC, Unit for Anesthesia, Karolinska University Hospital Huddinge, Stockholm, 2 Clinical Pharmacology, AstraZeneca R&D S¨odert¨alje, 3 Biostatistics, AstraZeneca R&D S¨odert¨alje, 4 Discovery Medicine, AstraZeneca R&D S¨odert¨alje, Norway, 5 Department of Anesthesiology and Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany Background and Aims: The methodological characteristics of human pain models used to predict efficacy of analgesics are critical, yet insufficiently documented. We have investigated the reproducibility and variability of a recently introduced model of evoked pain and hyperalgesia in human skin using continuous cutaneous electrical stimulation (CCES). Methods: High current density electrical stimulation (2Hz, 20−80 mA for 100 min using two electrodes in microdialysis fibers applied in parallel intracutaneously) was used to induce pain (numeric rating scale 6), axon reflex flare (Laser-Doppler), and areas of hyperalgesia and allodynia in 24 healthy subjects (14 male, 10 female aged 21−41 years) on four consecutive test sessions, one week apart. Results: CCES evoked reproducible pain and areas of hyperalgesia and allodynia with no significant difference or trend over time. Variability was lower within-subjects than between-subjects. The coefficients of variance (CV%) were 14 and 17, 37 and 48, and 59 and 67 for pain, hyperalgesia and allodynia respectively. Sex, previous experience of pain models or placement of electrodes did not influence the outcome. Power calculation revealed that 6 and 16 subjects respectively would be required to get a statistical power of 80%, to detect a 30% decrease in pain score and hyperalgesia in a cross-over design at significance level 5%. The method was well tolerated. Conclusions: CCES is a stable and reproducible method to evoke ongoing pain, hyperalgesia and allodynia. By choosing a crossover design, the model can detect efficacy of analgesics in a limited number of healthy subjects.
293 PAIN THRESHOLD AND STRESS-INDUCED ANALGESIA IN ANOREXIA NERVOSA AND HEALTHY WOMEN: THE ROLE OF STEROID HORMONES A. Yamamotova1 ° , H. Papezova2 , V. Kmoch2 . 1 Department of Normal, Pathological and Clinical Physiology, Charles University, 3rd Faculty of Medicine, Prague, 2 Department of Psychiatry, Charles University, 1st Faculty of Medicine, Prague, Czech Republic In healthy women, sensitivity to pain depends on levels of gonadal hormones. As estrogens have a pain-modulation effect, we assume that decreased levels of sex steroids contribute to weakened nociception in anorexia nervosa (AN). The aim of present study was to analyze association between adrenocortical and gonadal steroid hormones and thermal nociception in healthy women and in AN patients treated with hormonal substitution therapy. The pain threshold latencies on radiant heat stimuli were measured under rest and stress (mental arithmetic task) conditions in 20 DSM-IV diagnosed anorexia patients and in 21 healthy women. Blood samples were collected in a routine way in the morning hours and were taken for laboratory analyses of the plasma levels of estradiol, 17-OH progesterone, DHEA, DHEA-S and cortisol. AN patients taking HRT did not differ by any hormonal levels from controls. The pain threshold was significantly higher only in patients with the level of estradiol lower than 0.08 nmol/l. In both groups, the rest pain threshold negatively correlated with DHEA-S (r = −0.42, p = 0.008). The magnitude of stressinduced analgesia during mental arithmetic did not differ between groups and was estradiol independent. However, analgesia correlated positively in both groups with DHEA (r = 0.4974, p = 0.001), in anorexia with DHEA-S (r = 0.4833, p = 0.036) and in healthy women with 17-OH progesterone