Kimberly T. Sibille

Age and race effects on pain sensitivity and modulation among middle-aged and older adults.

UNLABELLED This study tested the effects of aging and race on responses to noxious stimuli using a wide range of stimulus modalities. The participants were 53 non-Hispanic blacks and 138 non-Hispanic white adults, ages 45 to 76 years. The participants completed a single 3-hour sensory testing session where responses to thermal, mechanical, and cold stimuli were assessed. The results suggest that there are selected age differences, with the older group less sensitive to warm and painful heat stimuli than middle-aged participants, particularly at the knee. This site effect supports the hypothesis that the greatest decrement in pain sensitivity associated with aging occurs in the lower extremities. In addition, there were several instances where age and race effects were compounded, resulting in greater race differences in pain sensitivity among the older participants. Overall, the data suggest that previously reported race differences in pain sensitivity emerged in our older samples, and this study contributes new findings in that these differences may increase with age in non-Hispanic blacks for temporal summation and both heat and cold immersion tolerance. We have added to the aging and pain literature by reporting several small to moderate differences in responses to heat stimuli between middle- and older-age adults. PERSPECTIVE This study found that the greatest decline in pain sensitivity with aging occurs in the lower extremities. In addition, race differences in pain sensitivity observed in younger adults were also found in our older sample.

Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis

OBJECTIVE Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. DESIGN In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. RESULTS Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. CONCLUSIONS These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.

Psychological Profiles and Pain Characteristics of Older Adults With Knee Osteoarthritis

To identify psychological profiles in persons with knee osteoarthritis (OA) and to determine the relationship between these profiles and specific pain and sensory characteristics, including temporal summation and conditioned pain modulation.

Racial and ethnic differences in older adults with knee osteoarthritis.

Knee osteoarthritis (OA) contributes significantly to disability in older individuals, and racial/ethnic minorities are disproportionately affected. The present study aimed to characterize differences in clinical and experimental pain, including pain inhibition, among older African American (AA) and non‐Hispanic white (NHW) subjects with knee OA.

The Association of Greater Dispositional Optimism With Less Endogenous Pain Facilitation Is Indirectly Transmitted Through Lower Levels of Pain Catastrophizing

UNLABELLED Dispositional optimism has been shown to beneficially influence various experimental and clinical pain experiences. One possibility that may account for decreased pain sensitivity among individuals who report greater dispositional optimism is less use of maladaptive coping strategies such as pain catastrophizing, a negative cognitive/affective response to pain. An association between dispositional optimism and conditioned pain modulation, a measure of endogenous pain inhibition, has previously been reported. However, it remains to be determined whether dispositional optimism is also associated with temporal summation (TS), a measure of endogenous pain facilitation. The current study examined whether pain catastrophizing mediated the association between dispositional optimism and TS among 140 older, community-dwelling adults with symptomatic knee osteoarthritis. Individuals completed measures of dispositional optimism and pain catastrophizing. TS was then assessed using a tailored heat pain stimulus on the forearm. Greater dispositional optimism was significantly related to lower levels of pain catastrophizing and TS. Bootstrapped confidence intervals revealed that less pain catastrophizing was a significant mediator of the relation between greater dispositional optimism and diminished TS. These findings support the primary role of personality characteristics such as dispositional optimism in the modulation of pain outcomes by abatement of endogenous pain facilitation and less use of catastrophizing. PERSPECTIVE Results from this study further support the body of evidence that attests to the beneficial effects of positive personality traits on pain sensitivity and pain processing. Further, this study identified diminished pain catastrophizing as an important mechanism explaining the inverse relation between dispositional optimism and endogenous pain facilitation.

Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis

OBJECTIVE Low circulating serum levels of 25-hydroxyvitamin D (referred to hereafter as vitamin D) have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels <20 ng/ml as deficient and levels of 21-29 ng/ml as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variations in vitamin D levels contribute to race differences in knee osteoarthritis pain. METHODS The sample consisted of 94 participants (74% women), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Their average age was 55.8 years (range 45-71 years). Participants completed a questionnaire on knee osteoarthritis symptoms and underwent quantitative sensory testing, including measures of sensitivity to heat-induced and mechanically induced pain. RESULTS Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to heat-induced and mechanically induced pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical pain. Group differences in vitamin D levels significantly predicted group differences in heat pain and pressure pain thresholds at the index knee and ipsilateral forearm. CONCLUSION These data demonstrate that race differences in experimental pain are mediated by differences in the vitamin D level. Vitamin D deficiency may be a risk factor for increased knee osteoarthritis pain in black Americans.

Enhanced Pain Sensitivity Among Individuals With Symptomatic Knee Osteoarthritis: Potential Sex Differences in Central Sensitization

Symptomatic knee osteoarthritis (OA) is a condition commonly associated with increased pain, disability, and functional limitations. Given the poor correspondence between radiographic evidence and clinical pain, central sensitization has been implicated as a potential mechanism underlying pain facilitation in knee OA. Sex may be a moderator of centrally mediated changes in knee OA pain; however, few studies have systematically assessed this. Therefore, the aim of this study was to examine differences in peripheral and central sensitization in men and women with symptomatic knee OA, as well as to determine whether these differences vary across age (middle age versus older age).

Chronic pain, perceived stress, and cellular aging: an exploratory study

BackgroundChronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL), a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of TL as a biological marker reflecting the burden of chronic pain and psychosocial stress has not yet been explored.FindingsThe relationship between chronic pain, stress, and TL was analyzed in 36 ethnically diverse, older adults, half of whom reported no chronic pain and the other half had chronic knee osteoarthritis (OA) pain. Subjects completed a physical exam, radiographs, health history, and psychosocial questionnaires. Blood samples were collected and TL was measured by quantitative polymerase chain reaction (qPCR). Four groups were identified characterized by pain status and the Perceived Stress Scale scores: 1) no pain/low stress, 2) no pain/high stress, chronic pain/low stress, and 4) chronic pain/high stress. TL differed between the pain/stress groups (p = 0.01), controlling for relevant covariates. Specifically, the chronic pain/high stress group had significantly shorter TL compared to the no pain/low stress group. Age was negatively correlated with TL, particularly in the chronic pain/high stress group (p = 0.03).ConclusionsAlthough preliminary in nature and based on a modest sample size, these findings indicate that cellular aging may be more pronounced in older adults experiencing high levels of perceived stress and chronic pain.

Testing the relation between dispositional optimism and conditioned pain modulation: Does ethnicity matter?

Greater dispositional optimism has been related to less severe pain; however, whether optimism is associated with endogenous pain modulation has not yet been examined. The beneficial effects of dispositional optimism often vary according to cultural dynamics. Thus, assessing optimism–pain relationships across different ethnic groups is warranted. This study sought to examine the association between optimism and conditioned pain modulation (CPM), and test whether this association differs according to ethnicity. Optimism and CPM were assessed in a sample of healthy, ethnically diverse young adults. CPM was determined by comparing pressure pain thresholds obtained before and during exposure to a cold pressor task. All participants completed a validated measure of dispositional optimism. Greater reported optimism was significantly associated with enhanced CPM, and the strength of this association did not vary according to individuals’ ethnic background. These findings suggest that an optimistic disposition may potentiate endogenous pain inhibition.

Telomeres and epigenetics: Potential relevance to chronic pain

Reciprocal interactions between stress and pain are well documented. Physical and psychosocial stressors, including childhood adversity, predict onset and exacerbation of clinical pain [17]. Conversely, chronic pain is a persistent endogenous stressor that can contribute to a cascade of psychosocial stressors including decreased activity level, reduced social support, and unemployment [5]. Despite growing appreciation for the importance of interactions between stress and pain, the mechanisms whereby the environment influences pain-related biological processes remain unclear. Further, the biological consequences of exposure to pain as a chronic stressor have received limited empirical attention. Converging work in telomere and epigenetics research indicates that adverse environmental experiences have a biological interface. The long-term effect of chronic stress appears to accelerate telomere shortening [13]. Epigenetic responses to the environment bridge stressful experiences with biological outcomes emphasizing the potential for epigenetic processes to influence individual pain experiences. Epigenome changes, occurring separate from and yet orchestrating the expression of the genome across the lifespan, may shape vulnerability and resilience factors implicated in chronic pain conditions [21]. Fig. 1 provides a heuristic model that conceptualizes the interactions between environmental influences and genome functioning. The model illustrates how stress and pain might influence molecular processes central to genome function. Specifically, events arising from both external and internal environments can (1) contribute to accelerated cellular aging, resulting in alterations in telomere length and/or (2) propel epigenetic modifications that ultimately modulate genomic regulation of peripheral and central pain processes. Advances in telomere and epigenetic research hold substantial promise for revealing how adverse environmental experiences are transduced to the genome to influence pain processing. In an effort to highlight the potential application of the molecular consequences of environmental stress to pain research, we discuss below evidence supporting the relevance of telomeres and epigenetic processes to chronic pain. Fig. 1 A heuristic model for conceptualizing the interactions between environmental influences and genome functioning. External factors are “outside” the individual, exogenous in nature, and represented by the outer light gray circle. Internal ... 2. Telomeres Pain elicits a stress response activating the autonomic, immune, and neuroendocrine systems [5]. While prior research has primarily addressed the biological profile of the acute stress response associated with clinical and experimental pain, the molecular consequences of chronic pain are not well understood. Identifying biological markers predicting the onset of chronic pain and reflecting the long-term impact of persistent pain would offer significant research and clinical utility. One such potential measure, leukocyte telomere length (TL), a marker of cellular aging, may benefit pain research given its association with the intensity and persistence of stress [10,38]. Telomeres are complexes comprising DNA and protein that cap and protect the ends of eukaryotic chromosomes, providing stability for replication and preventing fusions [4]. Telomeres are characterized by repetitive, single-strand DNA sequences that decrease in length with each cell division. As telomeres shorten to a critical length, cells typically become senescent; however, during this period, the risk of maladaptive cellular changes also increases [4,13]. Importantly, some cells are buffered by telomerase, a complex enzyme comprised of telomerase RNA, a reverse transcriptase, and accessory proteins. Telomerase adds telomeric DNA sequence repeats to the ends of chromosomes, providing protection, repair, and even potential lengthening of telomeres [4]. Although TL can be measured in various cells, a significant proportion of research has focused on peripheral blood mononuclear cells, leukocyte TL. Factors influencing mitosis in this cell population include oxidative stress, stress hormones, and inflammation [11–13,38]. In general, leukocyte TL shortens with chronological age, but the correlations are modest (r = −0.23 to −0.40) [10,28]. Some limitations identified in telomere research include differing measurement techniques, poor standardization across measures, and variability in TL across cell types within an individual [2]. Although conflicting findings exist, shorter leukocyte TL has been associated with age-related diseases, chronic mental and physical health conditions, and mortality [3,13,38], whereas longer TL has been associated with years of healthy life [27]. Growing evidence also indicates that TL is negatively associated with persistent psychosocial stress [13]; examples include caregiving stress [7,10] and a history of childhood adversity [18]. Importantly, in a group of adults providing extended care (average of 5 years) for a family member with Alzheimers disease, TL was not only shorter compared to control subjects, impaired immune functioning was also demonstrated [7]. The effects of stress on TL may be modulated by external and internal factors (Fig. 1). For example, evidence demonstrates that shorter TL is related to high levels of trait pessimism in women [29], while moderate exercise is associated with longer TL [20]. Telomerase, which can buffer leukocyte telomere shortening, is theorized to be a dynamic measure with demonstrated responsiveness to acute stressors [11], and has been indicated as an outcome measure in short-term clinical interventions [39]. Consistent with the concept of allostatic overload, chronic pain may be the result of, or contribute to, dysregulated stress response systems [23]. Inversely correlated with the duration of stress [10,38], TL appears to function as a barometer of the organisms cumulative response to long-term endogenous and exogenous stressors. As such, TL may serve as a measure of system burden, the consequence of chronic pain and associated stressors on an individual system. Recent findings indicate that older adults reporting chronic pain and high stress had significantly shorter leukocyte TL than individuals reporting no chronic pain and low stress [33]. Further research is needed to determine if telomere measures are markers of pain-related system burden, sensitive to individual variability in the onset and persistence of pain-related conditions.