Modulation of the Axon-Reflex Response to Local Heat by Reactive Oxygen Species (ROS) in subjects with Chronic Fatigue Syndrome

Marvin S. Medow, Arun Aggarwal, Ila Leigh Baugham, Zachary R. Messer, Julian M. Stewart


Local cutaneous heating causes vasodilation as an initial first peak, a nadir, and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau in healthy controls. The initial peak, due to C-fibre nociceptor-mediated axon reflexes, is blunted with local anesthetics, and may serve as a surrogate for the cutaneous response to peripheral heat. Chronic Fatigue Syndrome (CFS) subjects report increased perception of pain. To determine the role of ROS in this neurally-mediated response, we evaluated changes in cutaneous blood flow from local heat in 9 CFS subjects (16-22 years) compared to 8 healthy controls (18-26 years). We heated skin to 42°C and measured local blood flow as a percentage of maximum cutaneous vascular conductance (%CVCmax). While CFS subjects had significantly lower baseline flow (8.75±0.56 vs. 12.27±1.07 (%CVCmax , CFS vs. control)), there were no differences between groups to local heat. We then re-measured this with apocynin to inhibit NADPH oxidase, allopurinol to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce H2O2. Apocynin significantly increased baseline blood flow (before heat, 14.91±2.21 vs. 8.75±1.66) and the first heat peak (69.33±3.36 vs. 59.75±2.75). Allopurinol and ebselen only enhanced the first heat peaks (71.55±2.48 vs. 61.72±2.01 and 76.55±5.21 vs. 58.56±3.66, respectively). Tempol had no effect on local heating. None of these agents changed the response to local heat in control subjects. Thus the response to heat may be altered by local levels of ROS, particularly H2O2 in CFS subjects, and may be related to their hyperesthesia/ hyperalgesia.

  • Cutaneous Heat Response
  • Chronic Fatigue Syndrome
  • Reactive Oxygen SPecies
  • Microdialysis