Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

Abstract

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions.

Keywords: anterior cingulate cortex; central fatigue; immune system; inflammation; insula; motivation; multidimensional assessments; ventral striatum.

Figure 1

Features of central fatigue. Central fatigue is a complex symptom including several dimensions and concepts. It can be divided into physiological fatigue, a signal to rest and encourage energy preservation to prevent injuries, and pathological fatigue, when the adaptive function has been lost. Central fatigue is also comprised of several dimensions, namely physical fatigue, mental fatigue, and lack of motivation. These dimensions can be assessed in subjective or objective ways. Finally, the study of fatigue is further complicated by the difficulty in separating fatigue from close but distinct concepts, such as sleepiness and boredom.

Figure 2

Suggested mechanisms of inflammation-induced central fatigue. Inflammation is known to modulate several neuronal processes, including dorsal anterior cingulate cortex function, the mesolimbic pathway, and insula reactivity. During a physical or mental task, the inflammation-induced altered activation of these neuronal processes may contribute to the feeling of fatigue.