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.