Both sympathetic and parasympathetic nervous systems are involved in regulating pain states. The activity of these systems seems to become disturbed in states of chronic pain. This disruption in autonomic balance can be measured through the assessment of heart rate variability (HRV), that is, the variability of the interval between consecutive heart beats. However, there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions. Moreover, modern meta-analytical techniques have never been used to validate and consolidate the extent to which HRV may be decreased in chronic pain. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines, this study systematically evaluated and critically appraised the literature concerning HRV in people living with chronic pain. After screening 17,350 sources, 51 studies evaluating HRV in a chronic pain group met the inclusion criteria. Twenty-six moderate-high quality studies were included in quantitative meta-analyses. On average, the quality of studies was moderate. There were 6 frequency-domain and time-domain measures of HRV across a broad range of chronic pain conditions. High heterogeneity aside, pooled results from the meta-analyses reflected a consistent, moderate-to-large effect of decreased high-frequency HRV in chronic pain, implicating a decrease in parasympathetic activation. These effects were heavily influenced by fibromyalgia studies. Future research would benefit from wider use of standardised definitions of measurement, and also investigating the synergistic changes in pain state and HRV throughout the development and implementation of mechanism-based treatments for chronic pain.

BackgroundChronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.MethodsTherefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.ResultsSelf-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.ConclusionsOur results support the role of cytokines in the pathophysiology of CFS.

Recent studies have shown that perceiving the pain of others activates brain regions in the observer associated with both somatosensory and affective-motivational aspects of pain, principally involving regions of the anterior cingulate and anterior insula cortex. The degree of these empathic neural responses is modulated by racial bias, such that stronger neural activation is elicited by observing pain in people of the same racial group compared with people of another racial group. The aim of the present study was to examine whether a more general social group category, other than race, could similarly modulate neural empathic responses and perhaps account for the apparent racial bias reported in previous studies. Using a minimal group paradigm, we assigned participants to one of two mixed-race teams. We use the term race to refer to the Chinese or Caucasian appearance of faces and whether the ethnic group represented was the same or different from the appearance of the participant' own face. Using fMRI, we measured neural empathic responses as participants observed members of their own group or other group, and members of their own race or other race, receiving either painful or non-painful touch. Participants showed clear group biases, with no significant effect of race, on behavioral measures of implicit (affective priming) and explicit group identification. Neural responses to observed pain in the anterior cingulate cortex, insula cortex, and somatosensory areas showed significantly greater activation when observing pain in own-race compared with other-race individuals, with no significant effect of minimal groups. These results suggest that racial bias in neural empathic responses is not influenced by minimal forms of group categorization, despite the clear association participants showed with in-group more than out-group members. We suggest that race may be an automatic and unconscious mechanism that drives the initial neural responses to observed pain in others.