Postexertional neuroimmune exhaustion (PENE pen′-e)
‘Malaise’– a vague feeling of discomfort or fatigue [
41] – is an inaccurate and inadequate word for the pathological low-threshold fatigability and postexertional symptom flare. Pain and fatigue are crucial bioalarm signals that instruct patients to modify what they are doing in order to protect the body and prevent further damage. Postexertional neuroimmune exhaustion is part of the body’s global protection response and is associated with dysfunction in the regulatory balance within and between the nervous, immune and endocrine systems, and cellular metabolism and ion transport [
42–46]. The normal activity/rest cycle, which involves performing an activity, becoming fatigued and taking a rest whereby energy is restored, becomes dysfunctional.
Numerous papers document abnormal biological responses to exertion, such as loss of the invigorating effects of exercise [
20], decreased pain threshold [
47–49], decreased cerebral oxygen and blood volume/flow [
50–53], decreased maximum heart rate [
54], impaired oxygen delivery to muscles [
55], elevated levels of nitric oxide metabolites [
56] and worsening of other symptoms [
57]. Patients reach the anaerobic threshold and maximal exercise at a much lower oxygen consumption level [
58]. Reported prolonged effects of exertion include elevated sensory signalling to the brain [
59] that is interpreted as pain and fatigue [
29], elevated cytokine activity [
60], delay in symptom activation [
61] and a recovery period of at least 48 h [
57]. When an exercise test was given on two consecutive days, some patients experienced up to a 50% drop in their ability to produce energy on the second evaluation [
62]. Both submaximal and self-paced physiologically limited exercise resulted in postexertional malaise [
48].
