Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. Although the specific aetiological basis underlying these sex differences is unknown, it seems inevitable that multiple biological and psychosocial processes are contributing factors. For instance, emerging evidence suggests that genotype and endogenous opioid functioning play a causal role in these disparities, and considerable literature implicates sex hormones as factors influencing pain sensitivity. However, the specific modulatory effect of sex hormones on pain among men and women requires further exploration. Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.

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. 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.

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.

Objective 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-Americans (AAs) and non-Hispanic whites (NHWs) with knee OA. Methods AAs and NHWs with knee OA (n=267) completed clinical and functional pain assessments including quantitative sensory testing (QST). We hypothesized that 1) AAs would display lower pain tolerance and higher heat, mechanical and cold pain ratings compared to NHWs; 2) AAs would display greater temporal summation compared to NHWs; 3) AAs would display reduced pain inhibition compared to NHWs; 4) AAs would demonstrate greater clinical pain and poorer function relative to NHWs; and 5) QST would significantly predict clinical pain within each race/ethnicity. Results AAs displayed increased pain sensitivity, temporal summation and reduced pain inhibition than NHWs. AAs reported greater clinical pain and poorer function than NHWs. Race/ethnic differences in clinical pain became non-significant when controlling for education and income, whereas differences in QST remained highly significant. Although pain inhibition predicted clinical pain in both groups, different QST measures were additionally predictive of clinical pain within groups. Conclusion Our study establishes race/ethnic differences in experimental and clinical pain and function in older individuals with knee OA. Our findings that different QST measures were associated with clinical pain within race/ethnic groups while reduced pain inhibition was important in all participants warrants further study evaluating common and group-specific pathophysiological mechanisms contributing to clinical pain in OA.

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes.

Objective 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 vs. older-age). Methods Participants (N=288) between the ages of 45 and 85 completed a battery of quantitative sensory pain procedures assessing sensitivity to contact heat, cold pressor, mechanical pressure, and punctate stimuli. Differences in temporal summation (TS) were examined, as well as measures of clinical pain and functional performance. Results When compared to men, women exhibited greater sensitivity to multiple pain modalities (i.e., lower heat, cold, pressure thresholds/tolerances, greater TS of pain); however, there were no sex differences in clinical pain with the exception of greater widespread pain observed in women. Although there were select age-related differences in pain sensitivity, sex differences in pain varied minimally across age cohort. Conclusion Overall, these findings provide evidence for greater overall sensitivity to experimental pain in women with symptomatic knee osteoarthritis (OA), compared to men, suggesting that enhanced central sensitivity may be an important contributor to pain in this group.

Study Objectives: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy (ERRT) and extended prior research by including broad measures of mental health diffi culties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. Methods: Forty-seven individuals were randomized to treatment or waitlist control. Results:The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, signifi cant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. Conclusions S C I E N T I F I C I N V E S T I G A T I O N SN ightmares following trauma exposure are consistently associated with sleep disturbance, 1 posttraumatic stress disorder (PTSD) severity, 2 physiological arousal with or without PTSD, 3 and functional impairment over and above PTSD. 4,5 Moreover, chronic nightmares (CN) may be a signifi cant maintaining factor of psychological distress, because successful treatment of CN with cognitive behavioral therapy results in the reduction of symptoms of PTSD, depression, and nightmare-related panic. 6-8 Therefore, CN may pose a pernicious health problem independent of other psychopathology. Preliminary evidence suggests that psychological treatments which broadly target PTSD may have limited impact on sleep disturbances, 9-13 and pharmacological treatments appear to have little effect 14 or only a palliative effect 15 for some individuals. Thus, cognitive behavioral approaches specifi cally addressing sleep disturbances are now being evaluated in trauma-exposed samples. The present study is a replication of a randomized controlled trial (RCT) that examined the effi cacy of exposure, relaxation, and rescripting therapy (ERRT) to treat CN in trauma-exposed persons 7 and expands previous work by assessing the infl uence of treatment on facets of health that were not included in the fi rst RCT and examining physiological predictors of treatment response.The fi rst RCT demonstrated that ERRT reduced nightmare frequency and severity, related psychopathology, and improved sleep in trauma-expo...

FM patients show significant intra- and interindividual variability in pain, mood, and fatigue. Subgroups in mood and pain-related variability emerged, with phenotypic clusters differing across levels of pain intensity and social functioning. Better understanding of the processes affecting pain variability may facilitate targeted treatments for the control of pain.