Link Between Disease Activity, Sleep, Psychiatric Distress and Pain in RA
Link Between Disease Activity, Sleep, Psychiatric Distress and Pain in RA
Introduction Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA.
Methods Fifty-nine female RA patients completed questionnaires and underwent pressure pain threshold testing to assess hyperalgesia/allodynia at joint and non-joint sites. Blood samples were taken to measure C-reactive protein (CRP). The association between disease activity, sleep problems, psychiatric distress and pain threshold was assessed using Pearson/Spearman correlations and multivariable linear regression. Disease activity levels, sleep problems and psychiatric distress were compared between RA patients with fibromyalgia and RA patients without fibromyalgia.
Results In unadjusted analyses, CRP was not correlated with pain threshold, but tender joint count was inversely correlated with pain threshold at all sites (P ≤ 0.004). Sleep problems were associated with low pain threshold at all sites (P ≤ 0.0008). Psychiatric distress was associated with low pain threshold at the wrist and thumbnail (P ≤ 0.006). In multivariable linear regression models, CRP was inversely associated with wrist pain threshold (P = 0.003). Sleep problems were inversely associated with pain threshold at all sites (P ≤ 0.01), but psychiatric distress was not. Despite differences in pain threshold, CRP levels and sleep problems between RA patients with fibromyalgia and those without fibromyalgia, associations between these variables did not change when patients with fibromyalgia were excluded.
Conclusions Multivariable models are essential in analyses of pain. Among RA patients, inflammation is associated with heightened pain sensitivity at joints. In contrast, poor sleep is associated with diffuse pain sensitivity, as noted in central pain conditions such as fibromyalgia. Future studies examining pain sensitivity at joint and non-joint sites may identify patients with different underlying pain mechanisms and suggest alternative approaches to treating RA pain.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes significant pain. Despite the development of effective medications to treat inflammation, pain remains a priority for RA patients. Many RA patients report pain at non-joint sites, suffering from ongoing pain even when inflammation appears to be well controlled.
To date, most studies of pain in RA have focused on clinical pain severity. Kojima and colleagues recently reported independent effects of depression severity and inflammation on perceived pain in RA patients, emphasizing the complex relation between pain, inflammation and psychiatric distress. An earlier, cross-sectional study showed strong associations between clinical pain severity, sleep disturbance and mood. Although these studies provided critical information regarding clinical factors associated with pain severity, they did not quantify the patients' underlying pain sensitivity or yield information about pain mechanisms.
Pain sensitivity is measured by responses to experimental stimuli such as pressure. High pain thresholds represent low pain sensitivity, whereas low pain thresholds represent high pain sensitivity. Increased pain in response to normally painful stimuli is termed hyperalgesia, whereas pain in response to normally non-painful stimuli is termed allodynia. Pain thresholds may be measured at different locations to yield a comprehensive assessment of pain sensitivity at joint and non-joint sites.
Although it is well-documented that RA patients have lower pain thresholds than healthy controls, little is known about the factors associated with low pain thresholds and whether these factors impact pain thresholds on a peripheral, local level (i.e. at the joints) or on a central, widespread level. No studies of RA patients have incorporated assessments of pain threshold with comprehensive assessments of sleep problems and psychiatric distress, although these factors are: associated with reported pain severity and low pain threshold among healthy individuals and individuals with non-inflammatory pain syndromes; prevalent among the RA population; and associated with reported pain severity among RA patients.
As differences in pain sensitivity may shape the course of pain complaints and influence treatment decisions, it is important to understand the factors associated with enhanced pain sensitivity. In this study, we examined the relation between disease activity, sleep, psychiatric distress and pain threshold in RA patients. We hypothesized that both inflammatory and non-inflammatory factors are important mediators of pain sensitivity. Specifically, we hypothesized that objective measures of disease activity, such as C-reactive protein (CRP), are associated with pain threshold at RA-affected joints but not at sites distant from joints. We hypothesized that sleep and psychiatric distress are associated with decreased pain threshold at all sites, as is seen in chronic, non-inflammatory pain conditions such as fibromyalgia.
Abstract and Introduction
Abstract
Introduction Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA.
Methods Fifty-nine female RA patients completed questionnaires and underwent pressure pain threshold testing to assess hyperalgesia/allodynia at joint and non-joint sites. Blood samples were taken to measure C-reactive protein (CRP). The association between disease activity, sleep problems, psychiatric distress and pain threshold was assessed using Pearson/Spearman correlations and multivariable linear regression. Disease activity levels, sleep problems and psychiatric distress were compared between RA patients with fibromyalgia and RA patients without fibromyalgia.
Results In unadjusted analyses, CRP was not correlated with pain threshold, but tender joint count was inversely correlated with pain threshold at all sites (P ≤ 0.004). Sleep problems were associated with low pain threshold at all sites (P ≤ 0.0008). Psychiatric distress was associated with low pain threshold at the wrist and thumbnail (P ≤ 0.006). In multivariable linear regression models, CRP was inversely associated with wrist pain threshold (P = 0.003). Sleep problems were inversely associated with pain threshold at all sites (P ≤ 0.01), but psychiatric distress was not. Despite differences in pain threshold, CRP levels and sleep problems between RA patients with fibromyalgia and those without fibromyalgia, associations between these variables did not change when patients with fibromyalgia were excluded.
Conclusions Multivariable models are essential in analyses of pain. Among RA patients, inflammation is associated with heightened pain sensitivity at joints. In contrast, poor sleep is associated with diffuse pain sensitivity, as noted in central pain conditions such as fibromyalgia. Future studies examining pain sensitivity at joint and non-joint sites may identify patients with different underlying pain mechanisms and suggest alternative approaches to treating RA pain.
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes significant pain. Despite the development of effective medications to treat inflammation, pain remains a priority for RA patients. Many RA patients report pain at non-joint sites, suffering from ongoing pain even when inflammation appears to be well controlled.
To date, most studies of pain in RA have focused on clinical pain severity. Kojima and colleagues recently reported independent effects of depression severity and inflammation on perceived pain in RA patients, emphasizing the complex relation between pain, inflammation and psychiatric distress. An earlier, cross-sectional study showed strong associations between clinical pain severity, sleep disturbance and mood. Although these studies provided critical information regarding clinical factors associated with pain severity, they did not quantify the patients' underlying pain sensitivity or yield information about pain mechanisms.
Pain sensitivity is measured by responses to experimental stimuli such as pressure. High pain thresholds represent low pain sensitivity, whereas low pain thresholds represent high pain sensitivity. Increased pain in response to normally painful stimuli is termed hyperalgesia, whereas pain in response to normally non-painful stimuli is termed allodynia. Pain thresholds may be measured at different locations to yield a comprehensive assessment of pain sensitivity at joint and non-joint sites.
Although it is well-documented that RA patients have lower pain thresholds than healthy controls, little is known about the factors associated with low pain thresholds and whether these factors impact pain thresholds on a peripheral, local level (i.e. at the joints) or on a central, widespread level. No studies of RA patients have incorporated assessments of pain threshold with comprehensive assessments of sleep problems and psychiatric distress, although these factors are: associated with reported pain severity and low pain threshold among healthy individuals and individuals with non-inflammatory pain syndromes; prevalent among the RA population; and associated with reported pain severity among RA patients.
As differences in pain sensitivity may shape the course of pain complaints and influence treatment decisions, it is important to understand the factors associated with enhanced pain sensitivity. In this study, we examined the relation between disease activity, sleep, psychiatric distress and pain threshold in RA patients. We hypothesized that both inflammatory and non-inflammatory factors are important mediators of pain sensitivity. Specifically, we hypothesized that objective measures of disease activity, such as C-reactive protein (CRP), are associated with pain threshold at RA-affected joints but not at sites distant from joints. We hypothesized that sleep and psychiatric distress are associated with decreased pain threshold at all sites, as is seen in chronic, non-inflammatory pain conditions such as fibromyalgia.
