Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids).

Objective Among rheumatoid arthritis (RA) patients, pain may exist out of proportion to peripheral inflammation. This observation suggests that central nervous system pain amplification mechanisms, such as diminished conditioned pain modulation (CPM), may play a role in enhancing pain perception among some RA patients. We examined CPM, pressure pain threshold and pressure pain tolerance among RA patients compared to controls. Methods Fifty-eight female RA patients and 54 age-matched controls without chronic pain underwent quantitative sensory testing (QST) to assess CPM, pressure pain threshold and pressure pain tolerance. CPM was induced using a cold water bath, and pain threshold (when patients first felt pain) and tolerance (when pain was too much to bear) were assessed with an algometer. Associations between RA and QST measures were analyzed using linear regression. Sleep problems, mental health and inflammation were assessed as mediators of the relationship between RA and QST measures. Results Median CPM levels were 0.5 kg/cm2 (interquartile range (IQR) −0.1, 1.6) among RA patients compared to 1.5 kg/cm2 (IQR −0.1, 2.5) among controls (P = 0.04). Relative to controls, RA patients had lower pain threshold and tolerance at the wrists (P ≤ 0.05). Compared to controls, RA patients had greater problems with sleep, catastrophizing, depression and anxiety (P < 0.0001). Mediation analyses suggested that low CPM levels may be partially attributable to sleep disturbance (P = 0.04). Conclusion RA patients have impaired CPM relative to pain-free controls. Sleep problems may mediate the association between RA and attenuated CPM.

Background Exposure to heat, air pollution, and pollen are associated with health outcomes, including cardiovascular and respiratory disease. Studies assessing the health impacts of climate change have considered increased exposure to these risk factors separately, though they may be increasing simultaneously for some populations and may act synergistically on health. Our objective is to systematically review epidemiological evidence for interactive effects of multiple exposures to heat, air pollution, and pollen on human health. Methods We systematically searched electronic literature databases (last search, April 29, 2019) for studies reporting quantitative measurements of associations between at least two of the exposures and mortality from any cause and cardiovascular and respiratory morbidity and mortality specifically. Following the Navigation Guide systematic review methodology, we evaluated the risk of bias of individual studies and the overall quality and strength of evidence. Results We found 56 studies that met the inclusion criteria. Of these, six measured air pollution, heat, and pollen; 39 measured air pollution and heat; 10 measured air pollution and pollen; and one measured heat and pollen. Nearly all studies were at risk of bias from exposure assessment error. However, consistent exposure-response across studies led us to conclude that there is overall moderate quality and sufficient evidence for synergistic effects of heat and air pollution. We concluded that there is overall low quality and limited evidence for synergistic effects from simultaneous exposure to (1) air pollution, pollen, and heat; and (2) air pollution and pollen. With only one study, we were unable to assess the evidence for synergistic effects of heat and pollen. Conclusions If synergistic effects between heat and air pollution are confirmed with additional research, the health impacts from climate change-driven increases in air pollution and heat exposure may be larger than previously estimated in studies that consider these risk factors individually.

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