Gender Differences In Pain Sensitivity Research Articles

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats.

Studies on differences in brain structure and function according to sex are reported to contribute to differences in behavior and cognition. However, few studies have investigated brain structures or used tractography to investigate gender differences in pain sensitivity. The identification of tracts involved in sex-based structural differences that show pain sensitivity has remained elusive to date. Here, we attempted to demonstrate the sex differences in pain sensitivity and to clarify its relationship with brain structural connectivity. In this study, pain behavior test and brain diffusion tensor imaging (DTI) were performed in male and female rats and tractography was performed on the whole brain using fiber tracking software. We selected eight brain regions related to pain and performed a tractography analysis of these regions. Fractional anisotropy (FA) measurements using automated tractography revealed sex differences in the anterior cingulate cortex (ACC)-, prefrontal cortex (PFC)-, and ventral posterior thalamus-related brain connections. In addition, the results of the correlation analysis of pain sensitivity and DTI tractography showed differences in mean, axial, and radial diffusivities, as well as FA. This study revealed the potential of DTI for exploring circuits involved in pain sensitivity. The behavioral and functional relevance's of measures derived from DTI tractography is demonstrated by their relationship with pain sensitivity.

Advanced Interventions for Common Pain Conditions in Women

Pain syndromes affecting women have a significant global impact. There is increasing evidence that chronic pain affects a higher proportion of women than men around the world; unfortunately, women are less likely to receive treatment. Moreover, women generally experience more recurrent pain, more severe pain and longer-lasting pain than men. Pain conditions are more prevalent in women such as fibromyalgia, chronic pelvic pain and lumbopelvic pain during pregnancy and postpartum. Gender differences in pain sensitivity, pharmacological therapy, and nonpharmacological pain interventions have also been reported. It is becoming evident that gender differences in pain and its relief arise from an interaction of genetic, anatomical, physiological, neuronal, hormonal, psychological and social factors that modulate pain differently.

The roles of gender and profession on gender role expectations of pain in health care professionals.

IntroductionGender-related stereotypes of pain may account for some assessment and treatment disparities among patients. Among health care providers, demographic factors including gender and profession may influence the use of gender cues in pain management decision-making. The Gender Role Expectations of Pain Questionnaire was developed to assess gender-related stereotypic attributions of pain regarding sensitivity, endurance, and willingness to report pain, and has not yet been used in a sample of health care providers. The purpose of this study was to examine the presence of gender role expectation of pain among health care providers. It was hypothesized that health care providers of both genders would endorse gender stereotypic views of pain and physicians would be more likely than dentists to endorse these views.MethodsOne-hundred and sixty-nine providers (89 dentists, 80 physicians; 40% women) were recruited as part of a larger study examining providers’ use of demographic cues in making pain management decisions. Participants completed the Gender Role Expectations of Pain Questionnaire to assess the participant’s views of gender differences in pain sensitivity, pain endurance, and willingness to report pain.ResultsResults of repeated measures analysis of variance revealed that health care providers of both genders endorsed stereotypic views of pain regarding willingness to report pain (F(1,165)=34.241, P<0.001; d=0.479). Furthermore, female dentists rated men as having less endurance than women (F(1,165)=4.654, P=0.032; d=0.333).ConclusionThese findings affirm the presence of some gender-related stereotypic views among health care providers and suggest the presence of a view among health care providers that men are underreporting their pain in comparison to women. Future work can refine the effects of social learning history and other psychosocial factors that contribute to gender and provider differences in pain management decisions.

Effect of Age, Sex and Gender on Pain Sensitivity: A Narrative Review

Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention.

Genetic variation in opioid receptor genes and sensitivity to experimental pain in male and female healthy volunteers

Abstract Background/aims Pain is a common problem which significantly impacts on quality of life. Clinical pain is complicated to study due to numerous confounding variables. Normal volunteer models use standardised painful stimuli with resulting reduced phenotype variability. Current studies suggest an association between genetic variability and pain sensitivity. Methods Data from 50 healthy volunteers in three studies of multi-modal, multi-tissue experimental pain stimulation were included. Skin heat, muscle cuff pressure and visceral pressure were analysed. Genetic variants in the genes coding for the mu, delta and kappa opioid receptors (OPRM, OPRD and OPRK) were studied using multivariate regression modelling to investigate association with pain sensitivity. Results Reproducibility of baseline data for skin heat, muscle cuff pressure and visceral pressure between studies was confirmed (Cronbach’s α &gt; 0.8). Gender differences in pain sensitivity were seen. Females were more sensitive to skin heat and muscle pressure (P =0.006 and 0.02 respectively). Genetic associations were also found. OPRK was associated with both skin heat pain (P =0.009) and muscle cuff pain (P =0.003). Visceral pressure pain was not associated with either gender or genotype. Conclusion Genetic variations in the kappa opioid receptor appear to mediate different pain modalities. Gender remains an independent predictor of pain sensitivity.

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.

Sex Differences in Thermal Pain Sensitivity and Sympathetic Reactivity for Two Strains of Rat

Human females are more sensitive than males to brief nociceptive stimuli such as heat and cold. However, a more pronounced peripheral vasoconstriction by females than by males during prolonged nociceptive stimulation predicts that females would be more sensitive to prolonged cold but not heat stimulation. We tested this possibility with reflex (lick/guard) and operant escape and preference tests of sensitivity to prolonged stimulation of Long-Evans and Sprague-Dawley rats. Escape responses to cold stimulation revealed a greater sensitivity of females. In contrast, males were more sensitive to nociceptive heat stimulation. An operant preference test of relative sensitivity to cold or heat stimulation confirmed these results. Cold was more aversive than heat for females, but heat was more aversive than cold for males. Recordings of skin temperature during nociceptive heat stimulation were consistent with the results of operant testing. A reduction in skin temperature (peripheral vasoconstriction) during nociceptive stimulation should increase cold sensitivity as observed for females relative to males. Lick/guard testing did not confirm the results of operant testing. Lick/guard (L/G) responding to nociceptive heat stimulation was greater for females than for males. Female escape responses to heat were more variable than males, but L/G responding of males to the same stimulus was more variable than for females. A variety of chronic pain conditions are more prevalent for females, and psychological stress (with attendant sympathetic activation) is implicated in development and maintenance of these conditions. Therefore, understanding relationships between gender differences in pain sensitivity and sympathetic activation could shed light on mechanisms for some varieties of chronic pain.

Gender differences in brain activity evoked by muscle and cutaneous pain: A retrospective study of single-trial fMRI data

Gender greatly influences pain processing. Not only do females display greater pain sensitivity, many chronic pain conditions affect females more than males. Although gender-based differences in pain sensitivity may be related to cultural and social factors, animal studies also reveal gender differences in pain sensitivity, suggesting that physiological factors may contribute to differences in the processing of pain in males and females. It has been recently reported that noxious cutaneous heat stimuli evoke gender-based differences in activity in some brain regions. Given that most chronic pain conditions, including those with gender bias are of “deep” origin (e.g. arising in muscle, joints or viscera), we investigated whether gender differences also exist in the central processing of muscle pain. In 24 healthy adults we used functional magnetic resonance imaging (fMRI) to measure signal intensity changes during muscle and cutaneous pain induced by intramuscular and subcutaneous injections of hypertonic saline, respectively. In addition to activating the “pain neuromatrix”, i.e. cingulate, insular, somatosensory and cerebellar cortices, both muscle pain and cutaneous pain evoked gender-based differences in the mid-cingulate cortex, dorsolateral prefrontal cortex, hippocampus and cerebellar cortex. These differences may reflect differences in emotional processing of noxious information in men and women and may underlie the gender bias that exists in many chronic pain conditions.

Influence of pain and gender on impact loading during walking: A randomised trial

Background Knee joint osteoarthritis is painful and with an overweight of female incidence. The cardinal symptom is pain, which causes compensatory gait changes, and gender differences in pain sensitivity exist. Impact loadings at heel strike during walking are suspected as a co-factor in development of knee osteoarthritis. Thus the purpose of this study was to investigate the influence of experimental muscle pain and gender on generation and attenuation of impact loading during walking. Methods Ten healthy males and 10 healthy females were recruited. Impact loadings during walking were measured using force platforms and accelerometers attached to the tibia and sacrum. Impact ground reaction force peaks and loading rates, and peak accelerations were used to quantify impact loadings. Attenuation was quantified by means of a transfer function between the tibial and sacral accelerometer signals, and the relative peak acceleration reduction. Knee joint kinematics were collected using a three-dimensional movement analysis system. The study was a cross-over study and data were collected before, during, and after experimental vastus medialis pain and a control situation. Findings Experimental muscle pain did not affect generation or attenuation of impact loading in either gender. While the impact loading magnitude was similar across genders, lower loading rates and more efficient attenuation were observed in females. Interpretation It is concluded that generation and attenuation of impact loadings during walking are independent of quadriceps pain in both genders. The present study does not provide any evidence of the tested variables to address the gender differences in loading rates and attenuation.

Your Questions Answered

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed in this issue include titration of opioids for chronic nonmalignant pain, opioid tolerance versus resistance, opioids in osteoarthritis, oxy-codone in visceral pain, and gender differences in pain sensitivity.

Your Questions Answered

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed in this issue include titration of opioids for chronic nonmalignant pain, opioid tolerance versus resistance, opioids in osteoarthritis, oxy-codone in visceral pain, and gender differences in pain sensitivity.

Gender‐related differences in visceral perception in health and irritable bowel syndrome

Irritable bowel syndrome (IBS) is more common in female subjects, and IBS patients generally exhibit reduced pain thresholds to rectal distension. The aim of the present paper was to determine gender-related differences in rectal perception in both healthy controls and IBS patients. Fifty-nine IBS patients (age 20-65 years; mean, 39.2 years; 31 women, 28 men) with symptoms that fulfilled Rome-II criteria and 21 healthy controls (age 25-58 years; mean, 37.8 years; 11 women, 10 men) were recruited. Participants completed a questionnaire regarding bowel symptoms and psychological distress, and maximal tolerable pressures were evaluated via barostat tests. Although healthy women appear to have lower perception thresholds than men, significant gender differences in pain sensitivity were not detected (P > 0.05). In addition, female patients with IBS also exhibited no enhanced colorectal perception, as compared with male IBS patients (P > 0.05). No gender differences in visceral perception were determined to exist between the healthy controls and the IBS patients. Therefore, the increased prevalence of IBS in women may be related to another set of pathophysiological factors, and not to gender-related differences in visceroperception.

Cigarette smoking, stress-induced analgesia and pain perception in men and women

This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers ( P<0.05) when pain testing followed rest. Male smokers had greater threshold and tolerance to cold pressor pain than male nonsmokers ( P<0.05) after both rest and stress. Only women showed evidence for SIA, since women nonsmokers demonstrated greater ischemic pain threshold and tolerance following mental stress versus rest ( P<0.05), and all women reported lower thermal heat pain unpleasantness after stress versus rest ( P=0.05). Only nonsmokers showed expected inverse relationships between sympathetic and hypothalamic–pituitary–adrenal (HPA) axis reactivity measures and sensitivity to pain. Smokers showed evidence for blunted HPA-axis function at rest and stress. These results indicate that analgesia related to both being a smoker and stress is influenced by gender and pain modality. The reduced pain perception in smokers and absence of relationships between endogenous pain regulatory mechanisms and pain sensitivity may reflect a maladaptive response to chronic smoking.

Adrenocortical and hemodynamic predictors of pain perception in men and women

Research has demonstrated that women report more pain than men, and clinical observations suggest that attenuated adrenocortical activity is associated with high pain sensitivity. The extent to which cortisol concentrations and hemodynamics contribute to gender differences in pain sensitivity has not been investigated. Thirty-four women and 31 men performed the hand cold pressor test (CPT). Participants rated their pain every 15 s during a 90-s CPT and a 90-s post-CPT recovery period and reported pain using the McGill Pain Questionnaire (MPQ). Salivary cortisol samples and cardiovascular measures were collected prior to, during, and after the CPT. Women reported greater pain than men during and after the CPT and on the MPQ ( Ps<0.01). CPT disrupted the expected diurnal decline in cortisol, as shown by a significant increase in cortisol concentration post-CPT ( P<0.01) in men and women. Regression analyses revealed that pre-CPT cortisol concentrations predicted lower pain reports during and after CPT in men only ( P<0.01). Systolic blood pressure (BP) and stroke volume correlated negatively with pain reports only in women ( Ps<0.05). Controlling for potential confounding variables did not alter these relationships. The negative association between pre-CPT cortisol and pain perception in men and the association between BP and pain in women demonstrate different physiological predictors of pain perception in men and women.

Current Pain Research

Summary Current research has demonstrated that individual variation in pain of neural origins can be explained, in part, by the heritability of pain sensitivity and response to analgesics. Recent studies also have demonstrated gender differences in pain sensitivity and response to analgesics, which may explain the incidence and intensity of TMD signs and symptoms in women compared to men. It appears that the genetics of pain and pain sensitivity are expressed, in part, by alterations in the endogenous opioid pain modulatory system. Future clinicians and researchers will likely be able to apply genetic investigations and gene therapies to prevent, diagnose, and treat patients with acute and chronic orofacial pain conditions. The beneficiary of such high technique methods will be the patients and their families because genotype analyses can be used to provide individualized health care rather than care through traditionally based patient population means.

The influence of resting blood pressure and gender on pain responses.

Recent research suggests that resting blood pressure is inversely related to pain sensitivity, even among normotensives; however, most of these studies have included only male participants. To determine whether this hypoalgesic effect of blood pressure was also present in females, we investigated thermal and ischemic pain responses in a group of age-matched, normotensive females and males as a function of resting blood pressure. Thermal pain threshold and tolerance were determined, and a cross-modality thermal magnitude matching procedure was conducted, after which ischemic pain threshold and tolerance were determined using the submaximal effort tourniquet procedure. Systolic pressure, diastolic pressure, and heart rate were obtained using an automated blood pressure monitor with a pneumatic cuff positioned around the left ankle. Females provided higher normalized thermal magnitude estimates and a shorter time to ischemic pain tolerance, but no gender differences emerged on other pain measures. Systolic, diastolic, and mean arterial pressures were significantly correlated with thermal and ischemic pain responses among males but not females, with higher blood pressure being associated with lower pain sensitivity. After adjusting for resting blood pressure, the gender difference in normalized magnitude estimates was only marginally significant, and the gender difference in ischemic pain tolerance became nonsignificant. These findings are consistent with previous research indicating an inverse relationship between blood pressure and pain sensitivity. Additionally, the findings also suggest that blood pressure may partially moderate gender differences in pain sensitivity. Potential mechanisms and clinical implications of the current findings are discussed.