Introduction
Apart from the characteristic fatigue, patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience chronic widespread and persistent pain(1-3). A population-based study revealed that 94% of the persons diagnosed with ME/CFS report muscle pain, and 84% report joint pain(4). In fact, there is a great overlap between ME/CFS and fibromyalgia (FM), a disease particularly characterized by musculoskeletal pain(1).
As has been demonstrated in those with FM(2, 3), previous studies define central sensitization as the underlying mechanism maintaining chronic pain in ME/CFS patients(5-7). Central sensitization comprises hyper-excitement of the central neurons, altered sensory processing in the brain and malfunctioning descending pain inhibitory mechanisms(8). Furthermore, exercise-induced pain inhibition is not activated in patients with ME/CFS, resulting in lower pain thresholds and pain exacerbation after exercise(9-11).
There are several methods for estimating the intensity of a stimulus required to evoke a painful sensation in the skin: mechanical, chemical, electrical, and thermal(12). Algometry is a widely used technique for determining the effect of mechanical stimulation. It generates data on pressure pain thresholds (PPT)(13), or the degree of pressure required before the individual experiences pain. Lower thresholds indicate that pain is experienced with less pressure. Algometry is valid and reproducible, with high levels of interrater reliability(14-17). PPT is one of the most frequently methods used in FM to objectively assess severity(18-23).
In ME/CFS patients studies have shown that pain is increased following exercise stress testing(24, 25). Furthermore, studies have shown that submaximal physical stress reduced pain thresholds both in FM and non-FM ME/CFS patients, whereas in healthy controls pain thresholds increased(11, 26, 27).
Another aspect of pain perception that can be studied using algometry is temporal summation (windup), which refers to an increased pain perception in response to repetitive painful stimuli. A meta-analysis in FM patients showed a significant increase in windup compared to HC(28).
In a previous study in ME/CFS patients, we demonstrated that orthostatic stress results in a cerebral blood flow reduction, and that the blood flow reduction is associated with onset or worsening of pain(CNP2019). In the current study, we hypothesized that PPT would be reduced and windup would increase after orthostatic stress testing in ME/CFS patients. For this purpose PPT and windup were measured before and after a head-up tilt test (HUT) in ME/CFS patients and in healthy controls (HC). We also hypothesized that among ME/CFS participants, the presence of co-morbid FM would lead to lower PPT and increased windup compared to those without FM.