- Email: [email protected]
Effect of cocoa on endorphin levels and craniofacial muscle sensitivity in healthy individuals
Scientific presentations at the 2017 Annual Meeting / Scandinavian Journal of Pain 16 (2017) 165–188
(p < 0.01). Increasing systolic blood pressure in the control group. Diastolic blood pressure decrease in tramadol and placebo groups. In the tramadol group, we saw more frequently mild side effects. Conclusions: Tramadol gave no reduction in postoperative pain but an increased frequency of desaturation and side effects. Other drugs or other doses ought to be tried for this kind of postoperative pain management. http://dx.doi.org/10.1016/j.sjpain.2017.04.020 Tempo-spatial discrimination to non-noxious stimuli is better than for noxious stimuli Ken Steffen Frahm ∗ , Carsten Dahl Mørch, Ole Kæseler Andersen Integrative Neuroscience Group, Center for ® Neuroplasticity and Pain (CNAP), SMI , Department of Health Science & Technology, Aalborg University, 9220 Aalborg, Denmark E-mail address: [email protected] (K.S. Frahm). Aims: The exteroceptive sensory system is responsible for sensing external stimuli in relation to time and space. The aim of the study was to investigate the tempo-spatial properties of the exteroceptive system using laser heat and mechanical touch stimulation. Methods: 13 healthy subjects were stimulated in the volar forearm. Each subject was stimulated using two paradigms, a continuous stimulation along a continuous line on the skin, and a simultaneous 2-point stimulation. The line stimulations were delivered in both a distal and proximal direction with lengths of 25, 50, 75, and 100 mm. The 2-point stimulations were delivered with a point-to-point distance ranging from 10 to 100 mm, in steps of 10 mm. Both paradigms were delivered using painful heat (laser) stimulation and mechanical (touch) stimulation. Following each stimulation, subjects had to report the intensity (0–10 NRS, 3 being pain threshold) and either direction (line stimuli) or number of perceived points (2-point stimuli). Results: All four line lengths and both directions were reported correctly for all mechanical line stimulation (an accuracy of 100%). For laser line stimulation the directional discrimination threshold was 68.5 mm and 70.2 mm for distal and proximal directed stimuli, respectively. The 2-point discrimination threshold for heat stimulation (67.9 mm) was higher than for the mechanical stimulation (34.5 mm). NRS was significant higher for laser stimulations than for the mechanical stimulation for both line and 2-point stimulations. NRS increased both with line length and distance between the two points (ANOVA, p < 0.001). The average NRS was 3.15 and 0.91 for laser line and mechanical line stimulations, respectively. For 2point stimulation the average NRS was 3.72 and 1.06 for laser and mechanical stimulations, respectively. Conclusions: The findings indicate that the tempo-spatial acuity of the exteroceptive system is lower for noxious stimuli than for innoxious stimuli. This is possible due to the larger receptive fields of nociceptive neurons and/or less lateral inhibition. http://dx.doi.org/10.1016/j.sjpain.2017.04.021
171
The encoding of the thermal grill illusion in the human spinal cord F. Fardo a,b,∗ , N. Finnerup a , P. Haggard b a
Danish Pain Research Center, Aarhus University, Aarhus, Denmark b Institute of Cognitive Neuroscience, University College London, London, UK E-mail address: [email protected] (F. Fardo). Aims: The spatial alternation of innocuous cold and warm stimuli on the skin can paradoxically provoke a hot, burning sensation, known as the thermal-grill illusion (TGI). Whether the TGI depends on spinal or supraspinal integration mechanisms is still debated. To assess whether the TGI can be accounted by integration of cold and warm afferent signals in the spinal cord, we leveraged anatomical knowledge on the spatial arrangement of dermatomes and spinal segmental projections. Methods: We stimulated a series of skin locations on the right arm using one cold (∼20 ◦ C) and one warm thermode (∼40 ◦ C). The two stimulus locations had identical physical distance on the skin. However, the distance between the cold and heat projection signals in the spinal cord varied across three conditions. Cold and warm inputs were delivered (1) within the same dermatome (e.g., C5–C5); (2) across the dermatome boundary of two adjacent spinal segments (e.g., C5–C6); (3) across the dermatome boundary of two non-adjacent spinal segments (e.g., C5–T1). In two experiments, we obtained an estimate of the strength of the TGI by asking 32 healthy participants to complete a temperature matching task. Results: Participants overestimated the actual average temperature of the two thermodes (Exp. 1) and the cold temperature of one of the two thermodes (Exp. 2). However, this effect was significantly larger when cold and heat stimuli were delivered within the same dermatome (+6.57 ± 3.99 ◦ C and +9.88 ± 5.60 ◦ C) or between dermatomes projecting to adjacent spinal segments (+6.26 ± 4.44 ◦ C and +9.48 ± 5.83 ◦ C), compared to when cold and heat stimuli projected to non-adjacent spinal segments (+3.46 ± 4.46 ◦ C and +4.80 ± 3.21 ◦ C). Conclusions: These results demonstrate that the strength of the illusion is modulated by the segmental distance between cold and heat spinal signals, and show that the perceived quality and intensity of thermal stimuli depends upon low-level spatial summation mechanisms in the spinal cord. http://dx.doi.org/10.1016/j.sjpain.2017.04.022 Effect of cocoa on endorphin levels and craniofacial muscle sensitivity in healthy individuals A.H. Simoni, A. Randers, K. Jønsson, S. Arpe, J.N. Poulsen, P. Gazerani ∗ Department of Health Science and Technology, Aalborg University, Aalborg, Denmark E-mail address: [email protected] (P. Gazerani). Aims: Migraine headache is a recurrent incapacitating neurovascular disorder. A combination of events occurring within the trigeminovascular system has been suggested to underlie migraine pathogenesis, including release of inflammatory neuropeptides with subsequent effects on meningeal vessels and sensory transmission. Increased craniofacial muscle tenderness is also present in patients with migraine and a lower -endorphin concentration has been observed in these patients. Several external factors have been identified, which can modulate migraine. One such factor is cocoa, though controversies still exist whether this substance exerts pro-algesic or analgesic effects. The present study evaluated
172
Scientific presentations at the 2017 Annual Meeting / Scandinavian Journal of Pain 16 (2017) 165–188
effects of pure cocoa on a mechanically-induced headache model in healthy individuals. Serum -endorphin concentrations were also measured to identify if any changes occurred in response to cocoa consumption. Methods: Healthy volunteers (8 men and 7 women, average age: 22 ± 1.8 years) participated in a crossover study (approval number: N-20160015) consisting of two sessions with consumption of water or cocoa. A mechanical headband (custom-made, Aalborg University) was utilized to induce a moderate headache with pain rated as 4 on a Visual Analogue Scale (VAS0–10 ). In each session Pressure Pain Threshold (PPT) was measured by a hand held algometer at temporalis muscles and blood samples were collected to assess -endorphin levels by ELISA. ANOVA analysis and independent two-sample t-tests were performed for comparisons. P < 0.05 was considered as significant. Results: Consumption of cocoa compared to water did not change the pressure sensitivity in the craniofacial region without mechanical headband. No changes occurred in PPT with the mechanical headband either. Regardless of substance consumption (water/cocoa), endorphin levels remained unchanged. Conclusions: Findings demonstrated that pure cocoa in the applied concentration and within the timeline of this study did not seem to exert any analgesic or pro-algesic effect on the mechanical sensitivity of craniofacial muscles or -endorphin levels. http://dx.doi.org/10.1016/j.sjpain.2017.04.023 The impact of naloxegol treatment on gastrointestinal transit and colonic volume D. Grønlund a,b,∗ , A.E. Olesen a,b,c , J.L. Poulsen a,b , C. Brock a,b,c , A.M. Drewes a,b a
Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark b Department of Clinical Medicine, Aalborg University, Aalborg, Denmark c Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark E-mail address: [email protected] (D. Grønlund). Aims: Opioid treatment is associated with gastrointestinal (GI) side effects, known as opioid-induced bowel dysfunction (OIBD). Symptoms of OIBD are caused by opioid receptor activation in the enteric nervous system, which results in increased GI transit time and increased faecal volume in the colon. OIBD can be experimentally induced in healthy participants through oral oxycodone treatment. The aim of this study was to investigate whether administration of naloxegol, a peripherally restricted opioid antagonist, could reduce GI symptoms, GI transit time, and colorectal volume, using an experimental model of OIBD. Methods: In a double blind crossover trial, twenty-five healthy males were randomly assigned to a six day treatment of oral oxycodone in combination with either oral naloxegol or placebo. At baseline and at day six, participants filled in the Patient Assessment of Constipation Symptom questionnaire, and colorectal volume was quantified with a magnetic resonance imaging method. Participants swallowed a small electromagnetic capsule, which allowed determination of total and segmental GI transit times, using the 3D-Transit system. Results: In the established model of oxycodone induced OIBD, fewer GI symptoms were observed during naloxegol treatment, compared to placebo (P < 0.01). Naloxegol decreased median total transit time by 27% (56 vs 71 h, P < 0.05) and decreased colorectal transit time by 33% (45 vs 59 h, P < 0.01), compared to placebo.
No difference in colorectal volume was found between the two treatments. Conclusions: In an experimental model of OIBD, GI symptoms and GI transit time were reduced during treatment with naloxegol, compared to placebo. However, naloxegol treatment did not reduce colorectal volume. These findings add information on the potential of naloxegol to be used in prevention and treatment of OIBD. http://dx.doi.org/10.1016/j.sjpain.2017.04.024 Preoperative downregulation of long-noncoding RNA Meg3 in serum of patients with chronic postoperative pain after total knee replacement R. Giordano a,b,∗ , K.K. Petersen b , M. Santoro c , C. Pazzaglia c , M. Valeriani d , L. Arendt-Nielsen b a
Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark b Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark c Fondazione Don Gnocchi, Milan, Italy d Neurology Unit, Ospedale Bambino Gesù, Rome, Italy E-mail address: [email protected] (R. Giordano). Aims: The incidence of chronic pain after total knee replacement (TKR) is approx. 20%, why preoperative risk factors for the development of chronic postoperative pain are highly warranted. Studies have indicated that preoperative inflammatory markers hold prognostic information for the development of chronic postoperative pain. Long-non-coding-RNA (lncRNA) regulates the expression of genes related with e.g. inflammation. The current study aimed to investigate the preoperative influence of lncRNA on the development of chronic postoperative pain following TKR. Methods: 24 patients, who developed chronic postoperative pain and 12 patients with painfree recovery, were sampled from a larger clinical study. Preoperative serum samples were obtained from all patients and analyzed for potential lncRNA candidates. Briefly, total RNA was extracted from serum using miRNeasy Mini kit. cDNA samples were pre-amplified with RT2lncRNAPreAMP Primer Mix that contained specific set of primers to target genes of Human RT2lncRNA Inflammatory Response & Autoimmunity PCR Array. Further, the reaction (25 l) will be aliquoted into the wells of RT2lncRNA PCR Array Human Inflammatory Response & Autoimmunity. LncRNA-expressions were compared between the two groups using student’s t-test. Results: 19 patients were excluded due to the “cut-off” of the statistical analysis’s software that not included the samples because of genomic contamination, retro transcription and amplification’s low efficiency. A total of 13 patients were included (7 with pain, 6 without pain). The preliminary analysis found that the MEG3lncRNA (implicated in tumor vascularization suppressing) were downregulated in patients who developed chronic postoperative pain compared to patients with a normal recovery (fold change: −9.56, P < 0.05). Conclusions: Preoperative MEG-3 is downregulated in patients in risk of developing chronic postoperative pain following TKR. Future research, in larger cohorts should further investigate the role of MEG3 and hence the improvement of the cartilage
(p < 0.01). Increasing systolic blood pressure in the control group. Diastolic blood pressure decrease in tramadol and placebo groups. In the tramadol group, we saw more frequently mild side effects. Conclusions: Tramadol gave no reduction in postoperative pain but an increased frequency of desaturation and side effects. Other drugs or other doses ought to be tried for this kind of postoperative pain management. http://dx.doi.org/10.1016/j.sjpain.2017.04.020 Tempo-spatial discrimination to non-noxious stimuli is better than for noxious stimuli Ken Steffen Frahm ∗ , Carsten Dahl Mørch, Ole Kæseler Andersen Integrative Neuroscience Group, Center for ® Neuroplasticity and Pain (CNAP), SMI , Department of Health Science & Technology, Aalborg University, 9220 Aalborg, Denmark E-mail address: [email protected] (K.S. Frahm). Aims: The exteroceptive sensory system is responsible for sensing external stimuli in relation to time and space. The aim of the study was to investigate the tempo-spatial properties of the exteroceptive system using laser heat and mechanical touch stimulation. Methods: 13 healthy subjects were stimulated in the volar forearm. Each subject was stimulated using two paradigms, a continuous stimulation along a continuous line on the skin, and a simultaneous 2-point stimulation. The line stimulations were delivered in both a distal and proximal direction with lengths of 25, 50, 75, and 100 mm. The 2-point stimulations were delivered with a point-to-point distance ranging from 10 to 100 mm, in steps of 10 mm. Both paradigms were delivered using painful heat (laser) stimulation and mechanical (touch) stimulation. Following each stimulation, subjects had to report the intensity (0–10 NRS, 3 being pain threshold) and either direction (line stimuli) or number of perceived points (2-point stimuli). Results: All four line lengths and both directions were reported correctly for all mechanical line stimulation (an accuracy of 100%). For laser line stimulation the directional discrimination threshold was 68.5 mm and 70.2 mm for distal and proximal directed stimuli, respectively. The 2-point discrimination threshold for heat stimulation (67.9 mm) was higher than for the mechanical stimulation (34.5 mm). NRS was significant higher for laser stimulations than for the mechanical stimulation for both line and 2-point stimulations. NRS increased both with line length and distance between the two points (ANOVA, p < 0.001). The average NRS was 3.15 and 0.91 for laser line and mechanical line stimulations, respectively. For 2point stimulation the average NRS was 3.72 and 1.06 for laser and mechanical stimulations, respectively. Conclusions: The findings indicate that the tempo-spatial acuity of the exteroceptive system is lower for noxious stimuli than for innoxious stimuli. This is possible due to the larger receptive fields of nociceptive neurons and/or less lateral inhibition. http://dx.doi.org/10.1016/j.sjpain.2017.04.021
171
The encoding of the thermal grill illusion in the human spinal cord F. Fardo a,b,∗ , N. Finnerup a , P. Haggard b a
Danish Pain Research Center, Aarhus University, Aarhus, Denmark b Institute of Cognitive Neuroscience, University College London, London, UK E-mail address: [email protected] (F. Fardo). Aims: The spatial alternation of innocuous cold and warm stimuli on the skin can paradoxically provoke a hot, burning sensation, known as the thermal-grill illusion (TGI). Whether the TGI depends on spinal or supraspinal integration mechanisms is still debated. To assess whether the TGI can be accounted by integration of cold and warm afferent signals in the spinal cord, we leveraged anatomical knowledge on the spatial arrangement of dermatomes and spinal segmental projections. Methods: We stimulated a series of skin locations on the right arm using one cold (∼20 ◦ C) and one warm thermode (∼40 ◦ C). The two stimulus locations had identical physical distance on the skin. However, the distance between the cold and heat projection signals in the spinal cord varied across three conditions. Cold and warm inputs were delivered (1) within the same dermatome (e.g., C5–C5); (2) across the dermatome boundary of two adjacent spinal segments (e.g., C5–C6); (3) across the dermatome boundary of two non-adjacent spinal segments (e.g., C5–T1). In two experiments, we obtained an estimate of the strength of the TGI by asking 32 healthy participants to complete a temperature matching task. Results: Participants overestimated the actual average temperature of the two thermodes (Exp. 1) and the cold temperature of one of the two thermodes (Exp. 2). However, this effect was significantly larger when cold and heat stimuli were delivered within the same dermatome (+6.57 ± 3.99 ◦ C and +9.88 ± 5.60 ◦ C) or between dermatomes projecting to adjacent spinal segments (+6.26 ± 4.44 ◦ C and +9.48 ± 5.83 ◦ C), compared to when cold and heat stimuli projected to non-adjacent spinal segments (+3.46 ± 4.46 ◦ C and +4.80 ± 3.21 ◦ C). Conclusions: These results demonstrate that the strength of the illusion is modulated by the segmental distance between cold and heat spinal signals, and show that the perceived quality and intensity of thermal stimuli depends upon low-level spatial summation mechanisms in the spinal cord. http://dx.doi.org/10.1016/j.sjpain.2017.04.022 Effect of cocoa on endorphin levels and craniofacial muscle sensitivity in healthy individuals A.H. Simoni, A. Randers, K. Jønsson, S. Arpe, J.N. Poulsen, P. Gazerani ∗ Department of Health Science and Technology, Aalborg University, Aalborg, Denmark E-mail address: [email protected] (P. Gazerani). Aims: Migraine headache is a recurrent incapacitating neurovascular disorder. A combination of events occurring within the trigeminovascular system has been suggested to underlie migraine pathogenesis, including release of inflammatory neuropeptides with subsequent effects on meningeal vessels and sensory transmission. Increased craniofacial muscle tenderness is also present in patients with migraine and a lower -endorphin concentration has been observed in these patients. Several external factors have been identified, which can modulate migraine. One such factor is cocoa, though controversies still exist whether this substance exerts pro-algesic or analgesic effects. The present study evaluated
172
Scientific presentations at the 2017 Annual Meeting / Scandinavian Journal of Pain 16 (2017) 165–188
effects of pure cocoa on a mechanically-induced headache model in healthy individuals. Serum -endorphin concentrations were also measured to identify if any changes occurred in response to cocoa consumption. Methods: Healthy volunteers (8 men and 7 women, average age: 22 ± 1.8 years) participated in a crossover study (approval number: N-20160015) consisting of two sessions with consumption of water or cocoa. A mechanical headband (custom-made, Aalborg University) was utilized to induce a moderate headache with pain rated as 4 on a Visual Analogue Scale (VAS0–10 ). In each session Pressure Pain Threshold (PPT) was measured by a hand held algometer at temporalis muscles and blood samples were collected to assess -endorphin levels by ELISA. ANOVA analysis and independent two-sample t-tests were performed for comparisons. P < 0.05 was considered as significant. Results: Consumption of cocoa compared to water did not change the pressure sensitivity in the craniofacial region without mechanical headband. No changes occurred in PPT with the mechanical headband either. Regardless of substance consumption (water/cocoa), endorphin levels remained unchanged. Conclusions: Findings demonstrated that pure cocoa in the applied concentration and within the timeline of this study did not seem to exert any analgesic or pro-algesic effect on the mechanical sensitivity of craniofacial muscles or -endorphin levels. http://dx.doi.org/10.1016/j.sjpain.2017.04.023 The impact of naloxegol treatment on gastrointestinal transit and colonic volume D. Grønlund a,b,∗ , A.E. Olesen a,b,c , J.L. Poulsen a,b , C. Brock a,b,c , A.M. Drewes a,b a
Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark b Department of Clinical Medicine, Aalborg University, Aalborg, Denmark c Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark E-mail address: [email protected] (D. Grønlund). Aims: Opioid treatment is associated with gastrointestinal (GI) side effects, known as opioid-induced bowel dysfunction (OIBD). Symptoms of OIBD are caused by opioid receptor activation in the enteric nervous system, which results in increased GI transit time and increased faecal volume in the colon. OIBD can be experimentally induced in healthy participants through oral oxycodone treatment. The aim of this study was to investigate whether administration of naloxegol, a peripherally restricted opioid antagonist, could reduce GI symptoms, GI transit time, and colorectal volume, using an experimental model of OIBD. Methods: In a double blind crossover trial, twenty-five healthy males were randomly assigned to a six day treatment of oral oxycodone in combination with either oral naloxegol or placebo. At baseline and at day six, participants filled in the Patient Assessment of Constipation Symptom questionnaire, and colorectal volume was quantified with a magnetic resonance imaging method. Participants swallowed a small electromagnetic capsule, which allowed determination of total and segmental GI transit times, using the 3D-Transit system. Results: In the established model of oxycodone induced OIBD, fewer GI symptoms were observed during naloxegol treatment, compared to placebo (P < 0.01). Naloxegol decreased median total transit time by 27% (56 vs 71 h, P < 0.05) and decreased colorectal transit time by 33% (45 vs 59 h, P < 0.01), compared to placebo.
No difference in colorectal volume was found between the two treatments. Conclusions: In an experimental model of OIBD, GI symptoms and GI transit time were reduced during treatment with naloxegol, compared to placebo. However, naloxegol treatment did not reduce colorectal volume. These findings add information on the potential of naloxegol to be used in prevention and treatment of OIBD. http://dx.doi.org/10.1016/j.sjpain.2017.04.024 Preoperative downregulation of long-noncoding RNA Meg3 in serum of patients with chronic postoperative pain after total knee replacement R. Giordano a,b,∗ , K.K. Petersen b , M. Santoro c , C. Pazzaglia c , M. Valeriani d , L. Arendt-Nielsen b a
Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark b Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark c Fondazione Don Gnocchi, Milan, Italy d Neurology Unit, Ospedale Bambino Gesù, Rome, Italy E-mail address: [email protected] (R. Giordano). Aims: The incidence of chronic pain after total knee replacement (TKR) is approx. 20%, why preoperative risk factors for the development of chronic postoperative pain are highly warranted. Studies have indicated that preoperative inflammatory markers hold prognostic information for the development of chronic postoperative pain. Long-non-coding-RNA (lncRNA) regulates the expression of genes related with e.g. inflammation. The current study aimed to investigate the preoperative influence of lncRNA on the development of chronic postoperative pain following TKR. Methods: 24 patients, who developed chronic postoperative pain and 12 patients with painfree recovery, were sampled from a larger clinical study. Preoperative serum samples were obtained from all patients and analyzed for potential lncRNA candidates. Briefly, total RNA was extracted from serum using miRNeasy Mini kit. cDNA samples were pre-amplified with RT2lncRNAPreAMP Primer Mix that contained specific set of primers to target genes of Human RT2lncRNA Inflammatory Response & Autoimmunity PCR Array. Further, the reaction (25 l) will be aliquoted into the wells of RT2lncRNA PCR Array Human Inflammatory Response & Autoimmunity. LncRNA-expressions were compared between the two groups using student’s t-test. Results: 19 patients were excluded due to the “cut-off” of the statistical analysis’s software that not included the samples because of genomic contamination, retro transcription and amplification’s low efficiency. A total of 13 patients were included (7 with pain, 6 without pain). The preliminary analysis found that the MEG3lncRNA (implicated in tumor vascularization suppressing) were downregulated in patients who developed chronic postoperative pain compared to patients with a normal recovery (fold change: −9.56, P < 0.05). Conclusions: Preoperative MEG-3 is downregulated in patients in risk of developing chronic postoperative pain following TKR. Future research, in larger cohorts should further investigate the role of MEG3 and hence the improvement of the cartilage