Pain in patients with chronic fatigue syndrome: Does nitric oxide trigger central sensitisation?
Nijs J, Van de Velde B, De Meirleir K.
Department of Human Physiology, Faculty of Physical Education and Physical
Therapy, Vrije Universiteit Brussel (VUB), Belgium; Division of Musculoskeletal
Physical Therapy, Department of Health Sciences, Hogeschool Antwerpen (HA),
Belgium.
Previous studies have provided evidence supportive of the clinical importance
of widespread pain in patients with chronic fatigue syndrome (CFS): pain
severity may account for 26-34% of the variability in the CFS patient's
activity limitations and participation restrictions. The etiology of widespread
pain in CFS remains to be elucidated, but sensitisation of the central nervous
system has been suggested to take part of CFS pathophysiology. It is
hypothesised that a nitric oxide (NO) - dependent reduction in inhibitory
activity of the central nervous system and consequent central sensitisation
accounts for chronic widespread pain in CFS patients. In CFS patients,
deregulation of the 2',5'-oligoadenylate synthetase/RNase L pathway is
accompanied by activation of the protein kinase R enzyme. Activation of the
protein kinase R and subsequent nuclear factor-kappaB activation might account
for the increased production of NO, while infectious agents frequently
associated with CFS (Coxsackie B virus, Epstein-Barr Virus, Mycoplasma) might
initiate or accelerate this process. In addition, the evidence addressing
behavioural changes in CFS patients fits the central sensitisation-hypothesis:
catastrophizing, avoidance behaviour, and somatization may result in, or are
initiated by sensitisation of the central nervous system.