Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor–specific pain phenotype

Pain, vol. 165, pp. e1–e14

Abstract

ABSTRACT: Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor-sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex-mediated microcirculatory responses. Cold-pressor-sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor-mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber-mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water-exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Authors 8

1. R. Martel Aachen Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN) Medical Faculty Mannheim Germany. Martel is now with the Department of Pediatric Surgery Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel Germany. Weigand is now with the Department of Internal Medicine I Germany. Rolke is now with the Department of Palliative Care

   Heidelberg University · Vitos Orthopedic Clinic Kassel · University Medical Centre Mannheim · Medizinische Fakultät Mannheim · University of Regensburg · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. Martel is now with the Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel, Kassel, Germany. Weigand is now with the Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Rolke is now with the Department of Palliative Care, RWTH Aachen, Aachen, Germany

2. Georgios Papafragou Aachen Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN) Medical Faculty Mannheim Germany. Martel is now with the Department of Pediatric Surgery Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel Germany. Weigand is now with the Department of Internal Medicine I Germany. Rolke is now with the Department of Palliative Care

   Heidelberg University · Vitos Orthopedic Clinic Kassel · University Medical Centre Mannheim · Medizinische Fakultät Mannheim · University of Regensburg · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. Martel is now with the Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel, Kassel, Germany. Weigand is now with the Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Rolke is now with the Department of Palliative Care, RWTH Aachen, Aachen, Germany

3. Sylvia Weigand Aachen Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN) Medical Faculty Mannheim Germany. Martel is now with the Department of Pediatric Surgery Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel Germany. Weigand is now with the Department of Internal Medicine I Germany. Rolke is now with the Department of Palliative Care

   Heidelberg University · Vitos Orthopedic Clinic Kassel · University Medical Centre Mannheim · Medizinische Fakultät Mannheim · University of Regensburg · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. Martel is now with the Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel, Kassel, Germany. Weigand is now with the Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Rolke is now with the Department of Palliative Care, RWTH Aachen, Aachen, Germany

4. Roman Rolke
   Affiliation as printed

   Neurology and

5. Dirk Prawitt

   Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Pediatric Medicine, Medical Center, Johannes Gutenberg University, Mainz, Germany

6. Frank Birklein
   Affiliation as printed

   Neurology and

7. Rolf‐Detlef Treede Aachen Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN) Medical Faculty Mannheim Germany. Martel is now with the Department of Pediatric Surgery Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel Germany. Weigand is now with the Department of Internal Medicine I Germany. Rolke is now with the Department of Palliative Care

   Heidelberg University · Vitos Orthopedic Clinic Kassel · University Medical Centre Mannheim · Medizinische Fakultät Mannheim · University of Regensburg · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. Martel is now with the Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel, Kassel, Germany. Weigand is now with the Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Rolke is now with the Department of Palliative Care, RWTH Aachen, Aachen, Germany

8. Walter Magerl corresponding Aachen Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN) Medical Faculty Mannheim Germany. Martel is now with the Department of Pediatric Surgery Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel Germany. Weigand is now with the Department of Internal Medicine I Germany. Rolke is now with the Department of Palliative Care

   Heidelberg University · Vitos Orthopedic Clinic Kassel · University Medical Centre Mannheim · Medizinische Fakultät Mannheim · University of Regensburg · RWTH Aachen University

   Affiliation as printed

   Department of Neurophysiology, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. Martel is now with the Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. Papafragou is now with the Vitos Orthopädische Klinik Kassel, Kassel, Germany. Weigand is now with the Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Rolke is now with the Department of Palliative Care, RWTH Aachen, Aachen, Germany