Gender differences in pain modulation by diffuse noxious inhibitory controls: A systematic review

Over the last decade, extensive research has demonstrated sex differences in pain perception and modulation. Several factors have been proposed to account for the differences observed between men and women, including pain modulation through diffuse noxious inhibitory controls (DNIC). Studies investigating sex differences in DNIC have shown mixed results, with some reporting decreased DNIC effect in women compared with men, while others found no difference in DNIC between the sexes. Additional studies have investigated DNIC in both sexes without focusing on sex differences. This systematic review aimed to answer the following question: “In humans of reproductive age without chronic pain, are women more likely than men to have decreased Diffuse Noxious Inhibitory Controls?” Relevant studies were identified by computerized searches of Pubmed/Medline, Embase, Biosis, Web of Science, PsycInfo and Cochrane (from January 1980 through February 2009). The search was limited to human studies with no language restriction.     

Sex differences in perceptions of pain coping strategy usage

Sex differences are generally found in the perception and experience of pain, with women reporting more intense and frequent pain than men. One reason why such differences may occur has been linked to socially-acquired gender-role expectations associated with pain. Although there is evidence that men and women report using different pain coping strategies, we do not know the extent to which gender-specific expectations are associated with pain-related coping. The current study sought to examine this in more detail by administering a standard pain coping measures on three separate occasions, but with different instructions. Hundred and twenty two participants (57 male, 65 female) were asked to complete the coping measure as themselves, then again as they would expect the typical man and the typical woman to complete it. Results indicated that there were no significant differences between men and women in their own self-reported usage of pain coping strategies. However, there was general evidence to suggest that there are differences in stereotypical views of how men and women are thought to cope with pain. Furthermore, sex differences were also found in how participants viewed their own coping behaviours in comparison to that of the typical man and typical woman. These results confirm that alongside pain, men and women hold different gender-specific expectations with respect to certain pain coping strategies. Future research is required to examine whether these different coping expectations influence an individuals own choice of strategy, and whether this in turn affects actual pain experiences.     

Menstrual cycle phase does not influence gender differences in experimental pain sensitivity

Influence of menstrual cycle phase on experimental pain sensitivity in women and on gender differences in pain sensitivity was examined in 48 men and 49 women in response to cold pressor, heat, and ischemic pain. Each woman was tested at three points in their menstrual cycle in randomized order, the early follicular, late follicular, and luteal phases, while men were also tested three times, controlling for number of days between test sessions. Cycle phase was confirmed via serum hormone levels. As expected, women were significantly more sensitive to cold pain (p < .01), to heat pain (p < .0001), and to ischemic pain (p < .01) than men. However, pain perception during each task was not influenced by the menstrual cycle in women, nor did the menstrual cycle influence the magnitude of the gender differences in pain sensitivity. These results indicate that although women are more sensitive to a variety of noxious stimuli than men, menstrual cycle phase does not appear to moderate those differences in healthy men and women.     

Does past pain influence current pain: biological and psychosocial models of sex differences.

Previous studies have generally indicated sizeable sex differences for both laboratory pain reactivity and clinical pain reports. Numerous biological and psychosocial models have been invoked to account for these findings, but the laboratory and clinical findings have generally been examined in isolation. This paper reviews data which show a relationship between past clinical pain experiences and current responses to experimentally induced pain. Individuals with a greater pain history tend to show lower pain tolerance. Since women often have high pain experience levels and lower pain tolerance, one might ask whether the two factors are related. We review several models, based upon concepts of neonatal differences in pain reactivity, hypervigilance following early pain experiences, and concepts of peripheral and central sensitization or plasticity which might help to bridge the gap between clinical and experimental findings.     

Gender moderates the association between depression and disability in chronic pain patients.

Pain-related anxiety and depression are important correlates of disability amongst chronic pain patients. Furthermore, women may differ in their experience of pain, anxiety and depression when compared to men. The aim of the current study was to determine the relative contribution of anxiety and depression on disability in male and female chronic pain patients. The sample consisted of 260 patients (101 males, 159 females) referred to the Pain Management Unit at the Royal National Hospital for Rheumatic Diseases in Bath, UK. As part of an initial assessment, all patients completed measures of depression, pain-related anxiety and disability. As predicted, both anxiety and depression were found to be significant positive predictors of pain, number of medications used and disability. Although gender did not significantly predict disability, it did moderate the relationship between depression and disability, in that when depression was high, women report greater disability than men. Gender was also found to moderate the relationship between depression and number of medications used, in that a positive association was found for men, but not women. However, gender did not significantly moderate the relationship between anxiety and disability. Together these results not only suggest that gender is an important moderator of the relationship between emotional responses and disability, but that such associations may be related more to depression than anxiety.     

Sex differences in the adequacy of pain management among patients referred to a multidisciplinary cancer pain clinic

Few studies have evaluated sex differences in the adequacy of pain management in cancer. Existing studies have been marked by methodological limitations and results have been mixed. The present study sought to determine whether sex was associated with pain severity and pain management in cancer patients newly referred by their primary oncology team to a multidisciplinary cancer pain clinic. One hundred thirty-one cancer patients completed the Brief Pain Inventory-Short Form and medical chart review was conducted to obtain patients' clinical characteristics and pain treatment data. There were no differences between males and females in ratings of worst pain in the last week. Females were significantly less likely to have been prescribed high potency opioids by their primary oncology team and significantly more likely to report inadequate pain management as measured by Pain Management Index scores. These results suggest a sex bias in the treatment of cancer pain and support the routine examination of the effect of sex in cancer pain research.     

Gender effects in pain detection: Speed and accuracy in decoding female and male pain expressions

The ability to detect facial expressions of pain is crucial in eliciting prosocial behaviors towards the individual experiencing pain. Previous studies have shown that the sufferers' gender can affect the observers' explicit judgment of the pain face, thus suggesting its possible influence on pain decoding. The present study investigates whether the sufferer's gender affects the observer's reflexive or implicit detection of facial expression of pain. More specifically, we used implicit measures to test whether observers detect pained expression more quickly or accurately on male or female faces. In three experimental studies, we devised a set of stimuli using computer‐generated faces. In Experiment 1, prototypical female and male avatars with different facial expressions (pain, anger, disgust, and neutral) were displayed, while subjects' (N =34) accuracy and speed at identifying the expressions were recorded. In Experiment 2, participants (N =56) watched videos of the avatars displaying dynamic expressions and had to quickly and accurately identify each expression. In Experiment 3, participants (N =38) were shown an androgynous avatar face showing different expressions and were asked to identify the face as either female or male. Overall, we found that the target's gender affected the observer's reflexive decoding of the facial expression of pain. Specifically, the results showed that participants, regardless of their gender, were slower and less accurate in recognizing pain expressions (but not other expressions) on female faces. Furthermore, androgynous faces displaying pained expressions were more likely to be categorized as male than female. Several potential explanations are discussed.     

Gender and minority differences in the pain experience of people with spinal cord injury

OBJECTIVES: To examine gender and minority differences in the prevalence and severity of pain in people with traumatic-onset spinal cord injury (SCI) during follow-up, and to determine the relation of those differences to demographic characteristics, etiology of injury, and level and extent of the lesion. DESIGN: Survey and analysis of cross-sectional data using case-control methodology and multiple regression methods. SETTING: Model Spinal Cord Injury Systems (MSCIS). PARTICIPANTS: A total of 7379 individuals with traumatic-onset SCI from 16 MSCIS entered in the National Spinal Cord Injury Statistical Center database between 1998 and 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence and severity of pain as reported in follow-up surveys. RESULTS: Pain prevalence remained fairly stable over time, ranging from 81% at 1 year postinjury to 82.7% at 25 years. Pain was no more common in women than in men, nor did pain severity scores differ significantly. However, pain prevalence was significantly lower among nonwhites, although they tended to report a higher average pain severity score when pain was present. Also, people with SCI who were employed when injured, who had more than a high school education, and who were not tetraplegic reported a higher prevalence of pain. Pain interfered with work more often for women and nonwhites during some, but not all, follow-up years, and for those who were not employed at the time of interview, for those whose SCI was caused by violence, for those with paraplegia, and for those with incomplete SCI. CONCLUSIONS: Pain is a common and significant problem for the majority of people with SCI. It may interfere less frequently with work over time, which suggests that an adaptive process may be occurring. Gender differences in the pain experience did not emerge, but nonwhites tended to have a lower prevalence of pain. If pain was present, nonwhites tended to report more severe pain than did whites. Further research is needed to delineate the possible psychosocial and biomedical causes of these findings.     

多模式镇痛在髋关节置换术后疼痛患者中的应用

目的：探讨多模式镇痛在髋关节置换术后疼痛患者中的应用效果。方法选择全髋关节置换术患者108例,采用随机数字表法随机分为对照组和观察组各54例。对照组患者于术后48 h内给予镇痛泵（ PCA）镇痛,术后48 h停用PCA,改为口服塞来昔布,200 mg／次,bid,口服至术后第6天;观察组患者在给予PCA镇痛基础上,于术后第6小时开始口服塞来昔布,200 mg／次,bid,口服至术后第6天。记录两组患者手术日、术后第1,3,6天髋部切口疼痛,采用数字疼痛分级法（ NRS）评估,比较两组镇痛效果。结果观察组手术日、术后第1,3,6天NRS评分分别为（4．4±1．8）,（4．4±1．5）,（3．5±1．3）,（2．0±1．6）分,均低于对照组,两组比较差异有统计学意义（t值分别为74．131,106．335,223．316,217．195;P＜0．01）。结论采用PCA联合塞来昔布行多模式镇痛可提高髋关节置换术后患者的镇痛效果。     

Gender role expectations of pain is associated with pain tolerance limit but not with pain threshold

Gender role expectations of pain (GREP) was suggested to predict sex differences in pain perception. Our aim was to explore sex differences in GREP and investigate its relationship with heat-pain threshold (HPT) and heat-pain tolerance limit (HPTL). University students (115 males, 134 females) filled the GREP questionnaire. HPT and HPTL were measured in a sample of 72 students. Additionally, GREP values of the present sample were compared with those of the original, American sample to explore possible cultural effects.Both males and females perceive themselves (and their own sex in general) to be less sensitive to pain and less willing to report of pain than the opposite sex. Males perceived themselves and other men, to endure pain relatively similar to women whereas females perceived themselves and other women as less endurable to pain than men. HPT was similar for the two sexes but males had higher HPTL than females. Within each sex, HPTL correlated mainly with self’s perception of pain sensitivity. The American and Israeli samples differed in that Israeli males and females presented stronger stereotypical views towards same and opposite sexes.Both males and females held stereotypical “macho” attitude towards themselves with regard to pain sensitivity and willingness to report of pain however only females held stereotypical, “macho” attitude towards themselves with regard to pain endurance. The sex differences in GREP and in HPTL and the correlations between GREP items and experimental thresholds suggest that the relationship between GREP and experimental pain is complex and sex-specific. It also appears that GREP is affected by culture.     

Gender differences in amputation outcome

Purpose. To assess the influence of gender on the success of limb-fitting after amputation.

Methods. One-hundred and five successive in-patients admitted to an amputee rehabilitation ward were followed to assess the success of limb-fitting at discharge. The influence of demographic, clinical and social factors on the success of lower limb-fitting was assessed using linear regression analysis and group comparisons.

Results. There were 35 (33%) women in a cohort of 105 successive admissions. Men and women were comparable in terms of age, length of stay, medical comorbidity and level of amputation. Women were less likely to be successfully fitted with a prosthetic limb at discharge than men (42.9% vs 68.6%, p = 0.011), and more women lived alone (57.1% vs 38.6%, p = 0.021). Linear regression revealed that gender was an independent significant factor in the success of limb-fitting; age, level and cause of amputation, co-morbidity and length of stay were not significant factors.

Conclusions. Women were less likely to be successfully fitted with a lower limb prosthesis after amputation.     

Gender differences in amputation outcome

Purpose.?To assess the influence of gender on the success of limb-fitting after amputation.

Methods.?One-hundred and five successive in-patients admitted to an amputee rehabilitation ward were followed to assess the success of limb-fitting at discharge. The influence of demographic, clinical and social factors on the success of lower limb-fitting was assessed using linear regression analysis and group comparisons.

Results.?There were 35 (33%) women in a cohort of 105 successive admissions. Men and women were comparable in terms of age, length of stay, medical comorbidity and level of amputation. Women were less likely to be successfully fitted with a prosthetic limb at discharge than men (42.9% vs 68.6%, p = 0.011), and more women lived alone (57.1% vs 38.6%, p = 0.021). Linear regression revealed that gender was an independent significant factor in the success of limb-fitting; age, level and cause of amputation, co-morbidity and length of stay were not significant factors.

Conclusions.?Women were less likely to be successfully fitted with a lower limb prosthesis after amputation.     

Specialized multimodal outpatient treatment for children with chronic pain: Treatment pathways and long‐term outcome

Objective: Despite the increased recognition of paediatric chronic pain, centres for providing appropriate treatment are scarce, and much remains unknown about optimal treatment approaches. The purpose of this study was to investigate effectiveness of multimodal outpatient treatment (MOT) through the examination of treatment pathways and long‐term outcomes. Methods: Within an observational longitudinal study, 275 children (4–18 years) formed the study group and received MOT. Over a 12‐month period, we followed the progress of the study group to identify how many children completed treatment, how many continued treatment and how many were stepped‐up to more intensive treatment. To investigate significant and clinically relevant changes in primary and secondary outcomes the study group was assessed at three consecutive treatment sessions (initial session, 3‐, 6‐month visit) and 12 months following the initial session. Results: Analysis of treatment pathways showed that 1/3 of the children did not attend the prescribed second and third visit to the clinic. Cessation of treatment correlated with significant improvement. Only a small number of children were still in treatment at 12‐month follow‐up (12%) or needed more intensive treatment (11%). At 12‐month follow‐up, almost 70% of children in the study group were able to attend school regularly. Pain intensity, pain‐related disability and inappropriate coping strategies were significantly reduced at 3‐month visit and remained stable at the subsequent time points. Conclusions: MOT appears to be beneficial for children with chronic pain. A short intensive intervention (comprising of a total of 2.5‐h) can lead to substantial improvements even for severely affected children.     

Racial/ethnic differences in the experience of chronic pain

The purpose of this study was to examine racial/ethnic-related differences in a four-stage model of the processing of chronic pain. The subjects were 1557 chronic pain patients (White=1084, African American=473) evaluated at a pain management clinic at a large southeastern university medical center. Using an analysis of covariance controlling for pain duration and education, African American patients reported significantly higher levels of pain unpleasantness, emotional response to pain, and pain behavior, but not pain intensity than Whites. Differences were largest for the unpleasantness and emotion measures, particularly depression and fear. The groups differed by approximately 1.0 visual analogue scale unit, a magnitude that may be clinically significant. Racial/ethnic differences in the linear relationship between stages were also tested using structural equation modeling and LISREL-8. The results indicate differences in linear associations between pain measures with African Americans showing a stronger link between emotions and pain behavior than Whites.     

Visceral pain: gender differences in response to experimental and clinical pain.

Gender differences in response to visceral pain have important implications for experimental studies and when evaluating clinical pain. Few studies have in details explored specific gender differences in response to experimental stimulation of selected visceral organs or specific visceral diseases. Lower pain threshold to e.g. oesophageal distension has however been shown in females. The effect of female sex hormones on visceral function and pain is studied in greater details in both experimental and clinical studies. Pronounced differences in pain sensitivity are found across the menstrual phases. This may also interact with pharmacological interventions. For clinicians assessing the pain level of female patients in the reproductive age group should take into consideration the physiological and clinical effects of the menstrual cycle and the somatic segmental sites related to the uterus and cervix when clinically evaluating the pain and assessing for disease activity.     

Gender differences in funding among grant recipients in emergency medicine: A multicenter analysis

ObjectiveTo describe differences in funded grants between male and female faculty in two academic emergency departments.MethodsThis was a retrospective analysis of grant funding at two academic emergency departments from January 2012-September 2018. We queried the grants department databases at each institution and obtained records of all funded grants for emergency medicine (EM) faculty. We extracted the following information for each award: gender of the principal investigator (PI), PI academic rank, grant mechanism (government, institutional, industry, organizational), and percent effort. Differences by gender were compared using Chi-square or Fisher’s exact test and Wilcoxon-rank sum.ResultsOne-hundred and thirty grants were awarded to EM faculty at the two institutions during the study period. Of the funded grants, 35 (27%) of recipients were female. Among grant recipients, females held lower academic ranking than males (p-value < 0.001): Instructor (49% vs 51%), Assistant Professor (36% vs 64%), Associate Professor (9% vs 91%), and Professor (0% vs 100%), respectively. Organizational grants were dispersed equally between funded faculty, but females received a fewer government, industry, and institutional grants (p-value = 0.007). Female grant recipients were awarded a higher median percent of effort compared to males (14% [IQR: 3–51] vs 8% [IQR: 1–15], respectively, p-value = 0.023).ConclusionIn this multicenter analysis, gender discrepancies exist among funded grants of EM faculty. Male recipients had higher academic ranking than their female counterparts. Female recipients were less likely to have government, institutional, and industry grants but received a greater percent effort on funding that was awarded.     

Distinguishing patient satisfaction with treatment delivery from treatment effect: a preliminary investigation of patient satisfaction with symptoms after physical therapy treatment of low back pain

OBJECTIVE: To investigate the discrepancy between ratings of pain intensity and patient satisfaction by evaluating a questionnaire item that assesses patient satisfaction with treatment effect. DESIGN: Inception cohort. SETTING: Ambulatory care. PARTICIPANTS: Sixty-six consecutive patients referred to outpatient physical therapy (PT) with acute low back pain (LBP). INTERVENTION: PT using treatment-based classification guidelines. MAIN OUTCOME MEASURE: Patient satisfaction 6 months after receiving PT for LBP. RESULTS: Patient satisfaction with symptoms was considerably lower than the other patient satisfaction items. Patient satisfaction with symptoms was responsive to measures of treatment effect (Spearman rho range, .36-.44, P < .01) and with whether expectations were met (Spearman rho = .45, P < .01). Patients who were satisfied with symptoms reported higher physical function, lower pain intensity, and less symptom bothersomeness (P < .01) at 6 months. The 2 strongest absolute and unique predictors of patient satisfaction with symptoms at 6 months were whether treatment expectations were met and change in symptom bothersomeness. CONCLUSIONS: This study suggested that a questionnaire item assessing patient satisfaction with symptoms allows patients to distinguish between satisfaction with treatment effect and treatment delivery.     

A randomized controlled evaluation of an online chronic pain self management program

Internet-based educational and therapeutic programs (e-health applications) are becoming increasingly popular for a variety of psychological and physical disorders. We tested the efficacy of an online Chronic Pain Management Program, a comprehensive, fully self-directed and self-paced system that integrates social networking features and self-management tools into an interactive learning environment. Of 305 adult participants (196 women, 109 men), a total of 162 individuals with chronic pain were randomly assigned unsupervised access to the program for approximately 6 weeks; 143 were assigned to the wait-listed control group with treatment as usual. A comprehensive assessment was administered before the study and approximately 7 and 14 weeks thereafter. All recruitment, data collection, and participant involvement took place online. Participation was fully self-paced, permitting the evaluation of program effectiveness under real-world conditions. Intent-to-treat analysis that used linear growth models was used as the primary analytic tool. Results indicated that program utilization was associated with significant decreases in pain severity, pain-related interference and emotional burden, perceived disability, catastrophizing, and pain-induced fear. Further, program use led to significant declines in depression, anxiety, and stress. Finally, as compared to the wait-listed control group, the experimental group displayed a significant increase in knowledge about the principles of chronic pain and its management. Study limitations are considered, including the recognition that not all persons with chronic pain are necessarily good candidates for self-initiated, self-paced, interactive learning.     

Sex,gender, coping,and self‐efficacy: Mediation of sex differences in pain perception in children and adolescents

Sex differences in pain perception have been reported in an expanding literature based on adult samples in epidemiological as well as laboratory studies. Especially with respect to the latter, studies with children and adolescents do not consistently show that females report higher pain ratings and display lower pain tolerance than males. The first aim of the presented studies is to comparably examine sex differences in children and adolescents based on experimental and questionnaire approach indices of pain perception. The second aim is to examine the contribution of three prominent psychosocial factors (gender‐role expectations, coping with pain, and pain self‐efficacy) to these sex differences. In Study 1, a total of 118 children and adolescents from grades 5 to 9 were tested with the Cold Pressor Task (CPT) and a Pain Perception Questionnaire. In Study 2, 148 participants additionally reported on their gender‐role expectations, coping with pain, and pain self‐efficacy. Although the results reveal only medium‐sized correlations between the CPT and the questionnaire measures, both measures indicate substantial sex differences in pain perception in both studies. In Study 2, sex differences are also present for masculinity, femininity, catastrophizing as well as pain self‐efficacy. However, while the relation between sex and the CPT rating is partially mediated by pain self‐efficacy, catastrophizing partially mediates the relation between sex and the questionnaire based pain ratings. The results of both studies are discussed with respect to the difference between experimental assessments of pain perception and assessments by questionnaire in children and adolescents.