انتشار کنترل بازدارنده دردناک در سندرم خستگی مزمن با تاخیر همراه است: مطالعه تجربی

Deficient endogenous pain inhibition, e.g. Diffuse noxious inhibitory controls (DNIC), or hormonal abnormalities like hypocortisolism, could be responsible for chronic widespread pain in Chronic Fatigue Syndrome (CFS). Thirty-one CFS-patients with chronic pain and 31 healthy controls were subjected to spatial summation of thermal noxious stimuli by gradual immersion (ascending or descending) of the arm in warm water (46 °C). They rated pain intensity every 15 s. Every immersion took 2 min, alternated with 5 min rest. Before and after immersion, salivary cortisol was assessed. Overall pain ratings were higher in CFS-patients, but the evolution was not different between patients and controls, during both ascending and descending immersion. Pain intensity and immersed surface were only correlated during the descending session in both patients (r = .334) and controls (r = .346). When comparing the first and the last 15 s of every emersion, it was found that pain inhibition starts slower for CFS-patients in comparison to healthy subjects. Both pre- or post-values and cortisol response did not differ between controls and patients. The drop in cortisol was significantly correlated to pain intensity in CFS (r between .357 and .402). In addition to the hyperalgesia in CFS, DNIC react slower to spatial summation of thermal noxious stimuli. We found no evidence for hypocortisolism in CFS, and the cortisol response to nociception was not different in CFS compared to healthy subjects. In conclusion, delayed pain inhibition may play a role in chronic widespread pain in CFS but further research is required.

In Chronic fatigue syndrome (CFS) major concerns seem fatigue and increased fatigability. Research regarding chronic pain in CFS is lacking, although the majority of CFS-patients also suffers chronic widespread pain [20]. Considering the widespread localization of the pain and the absence of tissue damage, it has been suggested that central neural mechanisms may be responsible [19]. Central sensitization may be elicited by wind-up of N-methyl-d-aspartate receptors after prolonged firing of C-fiber nociceptors [3]. Besides, disruption of elements of descending pain inhibitory pathways can result in the equivalent of central sensitization [37]. To our knowledge, only the lack of analgesia following exercise is reported to document deregulated anti-nociceptive mechanisms in CFS [33]. In Fibromyalgia (FM), investigations concerning pain processing are abundant. Deregulation of endogenous pain inhibition has been documented by the default of analgesic effects due to exercise [13], [26] and [30] and in studies evaluating the efficacy of “Diffuse noxious inhibitory controls” (DNIC). DNIC rely on painful conditioning stimulation of one part of the body to inhibit pain in another part [4], to remove the “noise” and to focus on relevant stimuli. In contrast to healthy controls, applying conditioning noxious stimuli on one body part does not result in increased pain thresholds elsewhere in FM-patients [14] and [15]. DNIC also interfere with spatial summation of pain (SSP) [18]. SSP depends on the number of central neurons recruited [24] and thus the stimulated area. As the stimulated area increases, inhibitory interactions may take place between nociceptive afferent inputs within this area. For example, progressive immersion of the hand and arm in hot water might cause nociceptive input from the hand (=conditioning stimulus) to inhibit nociceptive input from the arm, as suggested by Marchand and Arsenault [18]. Deregulated DNIC could be documented in FM-patients by evaluating the SSP [11]. Besides neural mechanisms, hormonal abnormalities could cause altered pain processing. Cortisol is released in answer to pain and has the capacity to suppress pain [21]. Given the evidence for hypofunction of the hypothalamic-pituitary-adrenal axis in a proportion of CFS-patients [5] and [29], the relation between pain and cortisol in CFS-patients may be an interesting topic to consider. This study aimed at evaluating endogenous pain inhibition, more specific DNIC and the cortisol response, by spatially summating thermal nociceptive stimuli in CFS-patients with chronic widespread pain. We anticipated a lack of inhibitory efferent recruitment to counter nociceptive input in CFS-patients, leading to spatial summation and equal pain sensation during both increasing and decreasing immersion of the arm in hot water. In healthy controls, appropriate pain inhibition would compensate the increasing nociceptive input during increasing immersion of the arm. Complete recruitment of inhibitory efferents at the beginning of the descending immersion would lead to overcompensation of inhibition as the immersed surfaces decrease, resulting in lower pain intensities compared to the ascending immersion. In CFS-patients, this overcompensation would not occur due to the lack of complete inhibition recruitment, resulting in equal pain sensations. Furthermore, we assumed lower baseline cortisol levels and a blunted response to nociceptive stimuli in CFS-patients.