- Email: [email protected]
Sleep duration mediates the relationship between ethnic differences and experimental pain perception
S50
Abstracts
The Journal of Pain
(296) Does hyperbaric oxygen therapy attenuate secondary hyperalgesia areas induced by a heat injury in humans? V Rasmussen, A Landmark, M Werner, E Jansen, and P Rotbøll Nielsen; Copenhagen University Hospitals, Rigshospitalet, Copenhagen, Denmark Hyperbaric oxygen therapy (HBO) has, in animal experiments, been demonstrated to exert anti-inflammatory and mechanical anti-hypersensitivity effects in models of inflammation and neuropathy. Breathing 100% O2 at pressures greater than 1 ATA will increase the production of reactive oxygen and nitrogen species, and, impair b2-integrin function and chemokine production, explaining some of the anti-inflammatory effects of HBO, though the mechanisms are still incompletely understood. We hypothesized that the anti-inflammatory effect of HBO would attenuate secondary hyperalgesia areas (SHA) after a first degree heat injury in humans, using an open, randomized study design. Seventeen healthy subjects received two first degree heat injuries (HI) on the lower leg, with a minimum inter-session interval of 28 days. Induction of the HI by a contact thermode (12.5 cm2, 47.0 C, 7 min), was made after baseline assessments of mechanical primary and secondary hyperalgesia, erythema and SHA. Subjects were randomized in the first session to stay in normal ambient conditions (1 ATA, 21% O2) and in the second session to receive HBO (2.4 ATA, 100% O2) or vice versa. The assessments were repeated 30, 70, 100, 160 and 220 min after the HI. Subjects were randomized to, either, therapy in the first session with normal ambient conditions (1 ATA, 21% O2) and in the second session with 90 min of HBO (2.4 ATA, 100% O2), immediately after the HI, or, vice versa. A near-significant attenuation of the SHA, calculated as area-under-curve, was demonstrated from 886 cm2/min during ambient conditions compared to 569 cm2/min during HBO (P = 0.011). Our findings indicate that HBO may attenuate secondary hyperalgesia areas, compared to breathing under ambient conditions, in humans. The first degree heat injury is a sensitive model of anti-inflammatory effects of hyperbaric oxygen therapy in humans. Further research is needed. Supported by a grant from the ‘‘Direktør Ole Trock-Jansen og Hustrus Fond.’’
(298) Reproducibility of the heat/capsaicin sensitization model: a double blind, crossover, randomized, controlled study in healthy volunteers L Cavallone, M Montana, K Frey, J Joyal, and R Gereau; Washington University in St. Louis, St. Louis, MO A reliable method to produce hyperalgesia and allodynia in human healthy volunteers avoids the need to test novel analgesic drugs on vulnerable patients. A well characterized human experimental hyperalgesia model is the heat-capsaicin sensitization model.1,2 With this model, gabapentin significantly reduced cutaneous hyperalgesia compared to placebo.3 The thermal stimulators used in the original studies are no longer commercially available. Currently available thermodes are smaller (heated area max 9 cm2 vs. 12.515.7 cm2). It has been suggested that thermode size may be critical to create long-lasting hyperalgesia.4 Therefore, we decided to assess if previous findings could be confirmed when using a smaller probe. After IRB approval, 15 adult healthy volunteers were selected and trained to participate in two study sessions, scheduled one week apart. In each of the sessions, subjects received either gabapentin 1200 mg, or placebo, following exposure to the heat/ capsaicin cutaneous sensitization model.1,2 All subjects received both gabapentin and placebo in randomized order in the two sessions. Areas of hypersensitivity to brush stroke and VonFrey filament stimulation were measured after rekindling of skin sensitization at baseline and post-drug. A control group of 15 volunteers was exposed to identical sensitization procedures and schedule, but without administration of gabapentin or placebo. Differently from what previously reported, an identical reduction of sensitized areas was observed after gabapentin, placebo, and also in the control group. We conclude that smaller thermodes may not be suitable to reproduce stable areas of cutaneous sensitization. The similar reduction of sensitized areas in the control group and in the placebo group suggests ‘‘spontaneous fading’’ as opposed to a ‘‘placebo effect’’ in the placebo group, which had not been previously observed.3 (1. Petersen, NeuroReport, 1999; 2. Dirks, J Pain, 2003 ; 3. Dirks, Anesthesiology, 2002; 4. Yucel, Somatosensory & Motor Research, 2001.)
E13 Human Pain Models - Other
E14 Inflammation
(297) Sleep duration mediates the relationship between ethnic differences and experimental pain perception
(299) Daily cytokine fluctuations distinguish high pain from low pain days in women with fibromyalgia
L McCauley, K Bond, S Bounds, M Tripp, L Buenaver, D Tompkins, M Smith, J Haythornthwaite, and C Campbell; Johns Hopkins University, Baltimore, MD
E Stringer, K Baker, I Carroll, and J Younger; Stanford University, Palo Alto, CA
Ethnic differences in pain perception have been widely documented in both clinical and healthy populations. Sleep quality and duration also vary between clinical and healthy populations. However, the effect of sleep on the relationship between ethnic differences and pain has not been previously examined. In this study, healthy subjects (N=39, mean age=25.53, 48.72% female) participated in psychophysical pain testing involving pain induction by applying topical (10%, .35g) capsaicin cream evenly to a temperature controlled area on the back of the hand. Pain ratings were obtained every minute for 90 minutes using the 0-100 scale. Participants were also asked to wear an Actigraphâ (a watch-like device worn on the non-dominant wrist) to record their daily wake and sleep patterns for one week. From this data a variety of sleep variables were calculated including sleep duration. Non-Hispanic African American (N=20) and Caucasian healthy controls (N=19) completed these procedures. African American participants reported significantly greater pain (p=.036; mean=54.55, SD=28.03) compared to Caucasian participants (mean=36.99, SD=23.54). African Americans also obtained less total hours of sleep (p=.007; mean= 6.6, SD=0.96) compared to Caucasians (mean=7.5, SD=0.91). To examine the role of sleep duration in mediating the relationship between ethnicity and pain, a statistical bootstrapping technique recommended for tests of indirect effects was used. When sleep duration was included in the ethnicity/capsaicin pain model, the effect of race on pain rating was no longer significant (t=-1.344 p=.189). These results suggest that the greater capsaicin-related pain observed in African Americans may be explained, at least partially, by a significantly shorter sleep duration (t=-2.367 p=.016). These results also indicate that decreased sleep duration in African Americans may strongly affect pain perception; consequently, assessment of sleep in this population may be an important clinical factor to consider and address in chronic pain treatment.
Fibromyalgia (FM) is a devastating chronic pain condition, affecting approximately 5 million Americans. The condition is diagnosed primarily in women and is characterized by widespread musculoskeletal pain, heightened pressure pain sensitivity, decreased mobility, profound fatigue, poor sleep quality, and impaired cognitive ability. The underlying cause of FM is currently unknown leading to a controversy around the legitimacy of the diagnosis, with no objective diagnostic tests, and no effective treatments specifically targeting the underlying pathology. Many studies using a single time-point approach have demonstrated a role of inflammation in FM, but with contradictory results. These approaches overlook important features of FM, such as daily fluctuations in pain severity. Here, we implemented a novel, high-frequency, longitudinal study design to investigate the role of cytokines in FM pathophysiology. Eight women meeting the American College of Rheumatology’s diagnostic criteria for FM underwent 25 consecutive days of blood draws and self-reporting of FM symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 200 serum samples collected. Our goal was to determine if a machine learning algorithm, using all 51 cytokines, could distinguish high from low pain days. Machine learning algorithms use multivariate approaches to achieve greater sensitivity than massive univariate tests for identifying complex predictor-outcome relationships. The dataset included the nine most severe pain days and nine least severe pain days for each of the eight participants, for a total of 144 cases. We used Weka’s LibLINEAR support vector machine algorithm with a cost function C = 1 and a 10-fold independent cross-validation. The LibLINEAR algorithm distinguished high pain from low pain days with 79.9% accuracy. High pain days were classified with 80.6% sensitivity and 79.2% specificity. Our results suggest that daily fluctuations in circulating cytokines may drive FM symptom severity.
Abstracts
The Journal of Pain
(296) Does hyperbaric oxygen therapy attenuate secondary hyperalgesia areas induced by a heat injury in humans? V Rasmussen, A Landmark, M Werner, E Jansen, and P Rotbøll Nielsen; Copenhagen University Hospitals, Rigshospitalet, Copenhagen, Denmark Hyperbaric oxygen therapy (HBO) has, in animal experiments, been demonstrated to exert anti-inflammatory and mechanical anti-hypersensitivity effects in models of inflammation and neuropathy. Breathing 100% O2 at pressures greater than 1 ATA will increase the production of reactive oxygen and nitrogen species, and, impair b2-integrin function and chemokine production, explaining some of the anti-inflammatory effects of HBO, though the mechanisms are still incompletely understood. We hypothesized that the anti-inflammatory effect of HBO would attenuate secondary hyperalgesia areas (SHA) after a first degree heat injury in humans, using an open, randomized study design. Seventeen healthy subjects received two first degree heat injuries (HI) on the lower leg, with a minimum inter-session interval of 28 days. Induction of the HI by a contact thermode (12.5 cm2, 47.0 C, 7 min), was made after baseline assessments of mechanical primary and secondary hyperalgesia, erythema and SHA. Subjects were randomized in the first session to stay in normal ambient conditions (1 ATA, 21% O2) and in the second session to receive HBO (2.4 ATA, 100% O2) or vice versa. The assessments were repeated 30, 70, 100, 160 and 220 min after the HI. Subjects were randomized to, either, therapy in the first session with normal ambient conditions (1 ATA, 21% O2) and in the second session with 90 min of HBO (2.4 ATA, 100% O2), immediately after the HI, or, vice versa. A near-significant attenuation of the SHA, calculated as area-under-curve, was demonstrated from 886 cm2/min during ambient conditions compared to 569 cm2/min during HBO (P = 0.011). Our findings indicate that HBO may attenuate secondary hyperalgesia areas, compared to breathing under ambient conditions, in humans. The first degree heat injury is a sensitive model of anti-inflammatory effects of hyperbaric oxygen therapy in humans. Further research is needed. Supported by a grant from the ‘‘Direktør Ole Trock-Jansen og Hustrus Fond.’’
(298) Reproducibility of the heat/capsaicin sensitization model: a double blind, crossover, randomized, controlled study in healthy volunteers L Cavallone, M Montana, K Frey, J Joyal, and R Gereau; Washington University in St. Louis, St. Louis, MO A reliable method to produce hyperalgesia and allodynia in human healthy volunteers avoids the need to test novel analgesic drugs on vulnerable patients. A well characterized human experimental hyperalgesia model is the heat-capsaicin sensitization model.1,2 With this model, gabapentin significantly reduced cutaneous hyperalgesia compared to placebo.3 The thermal stimulators used in the original studies are no longer commercially available. Currently available thermodes are smaller (heated area max 9 cm2 vs. 12.515.7 cm2). It has been suggested that thermode size may be critical to create long-lasting hyperalgesia.4 Therefore, we decided to assess if previous findings could be confirmed when using a smaller probe. After IRB approval, 15 adult healthy volunteers were selected and trained to participate in two study sessions, scheduled one week apart. In each of the sessions, subjects received either gabapentin 1200 mg, or placebo, following exposure to the heat/ capsaicin cutaneous sensitization model.1,2 All subjects received both gabapentin and placebo in randomized order in the two sessions. Areas of hypersensitivity to brush stroke and VonFrey filament stimulation were measured after rekindling of skin sensitization at baseline and post-drug. A control group of 15 volunteers was exposed to identical sensitization procedures and schedule, but without administration of gabapentin or placebo. Differently from what previously reported, an identical reduction of sensitized areas was observed after gabapentin, placebo, and also in the control group. We conclude that smaller thermodes may not be suitable to reproduce stable areas of cutaneous sensitization. The similar reduction of sensitized areas in the control group and in the placebo group suggests ‘‘spontaneous fading’’ as opposed to a ‘‘placebo effect’’ in the placebo group, which had not been previously observed.3 (1. Petersen, NeuroReport, 1999; 2. Dirks, J Pain, 2003 ; 3. Dirks, Anesthesiology, 2002; 4. Yucel, Somatosensory & Motor Research, 2001.)
E13 Human Pain Models - Other
E14 Inflammation
(297) Sleep duration mediates the relationship between ethnic differences and experimental pain perception
(299) Daily cytokine fluctuations distinguish high pain from low pain days in women with fibromyalgia
L McCauley, K Bond, S Bounds, M Tripp, L Buenaver, D Tompkins, M Smith, J Haythornthwaite, and C Campbell; Johns Hopkins University, Baltimore, MD
E Stringer, K Baker, I Carroll, and J Younger; Stanford University, Palo Alto, CA
Ethnic differences in pain perception have been widely documented in both clinical and healthy populations. Sleep quality and duration also vary between clinical and healthy populations. However, the effect of sleep on the relationship between ethnic differences and pain has not been previously examined. In this study, healthy subjects (N=39, mean age=25.53, 48.72% female) participated in psychophysical pain testing involving pain induction by applying topical (10%, .35g) capsaicin cream evenly to a temperature controlled area on the back of the hand. Pain ratings were obtained every minute for 90 minutes using the 0-100 scale. Participants were also asked to wear an Actigraphâ (a watch-like device worn on the non-dominant wrist) to record their daily wake and sleep patterns for one week. From this data a variety of sleep variables were calculated including sleep duration. Non-Hispanic African American (N=20) and Caucasian healthy controls (N=19) completed these procedures. African American participants reported significantly greater pain (p=.036; mean=54.55, SD=28.03) compared to Caucasian participants (mean=36.99, SD=23.54). African Americans also obtained less total hours of sleep (p=.007; mean= 6.6, SD=0.96) compared to Caucasians (mean=7.5, SD=0.91). To examine the role of sleep duration in mediating the relationship between ethnicity and pain, a statistical bootstrapping technique recommended for tests of indirect effects was used. When sleep duration was included in the ethnicity/capsaicin pain model, the effect of race on pain rating was no longer significant (t=-1.344 p=.189). These results suggest that the greater capsaicin-related pain observed in African Americans may be explained, at least partially, by a significantly shorter sleep duration (t=-2.367 p=.016). These results also indicate that decreased sleep duration in African Americans may strongly affect pain perception; consequently, assessment of sleep in this population may be an important clinical factor to consider and address in chronic pain treatment.
Fibromyalgia (FM) is a devastating chronic pain condition, affecting approximately 5 million Americans. The condition is diagnosed primarily in women and is characterized by widespread musculoskeletal pain, heightened pressure pain sensitivity, decreased mobility, profound fatigue, poor sleep quality, and impaired cognitive ability. The underlying cause of FM is currently unknown leading to a controversy around the legitimacy of the diagnosis, with no objective diagnostic tests, and no effective treatments specifically targeting the underlying pathology. Many studies using a single time-point approach have demonstrated a role of inflammation in FM, but with contradictory results. These approaches overlook important features of FM, such as daily fluctuations in pain severity. Here, we implemented a novel, high-frequency, longitudinal study design to investigate the role of cytokines in FM pathophysiology. Eight women meeting the American College of Rheumatology’s diagnostic criteria for FM underwent 25 consecutive days of blood draws and self-reporting of FM symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 200 serum samples collected. Our goal was to determine if a machine learning algorithm, using all 51 cytokines, could distinguish high from low pain days. Machine learning algorithms use multivariate approaches to achieve greater sensitivity than massive univariate tests for identifying complex predictor-outcome relationships. The dataset included the nine most severe pain days and nine least severe pain days for each of the eight participants, for a total of 144 cases. We used Weka’s LibLINEAR support vector machine algorithm with a cost function C = 1 and a 10-fold independent cross-validation. The LibLINEAR algorithm distinguished high pain from low pain days with 79.9% accuracy. High pain days were classified with 80.6% sensitivity and 79.2% specificity. Our results suggest that daily fluctuations in circulating cytokines may drive FM symptom severity.