Spousal responses are differentially associated with clinical variables in women and men with chronic pain

OBJECTIVES: Spousal responses have been related to clinical variables in patients with chronic pain. For example, solicitous responses from spouses have been associated with greater levels of pain and disability among patients with chronic pain. However, few investigators have determined whether spousal solicitousness produces different effects in women versus men with chronic pain. The present study examined pain reports, medication use, psychosocial factors, functional measures, and pain tolerance in patients with chronic pain. METHODS: Subjects included 114 female and 213 male chronic pain patients, who described their spouses as either high or low in solicitousness on the Multidimensional Pain Inventory. Measures of pain severity, affective distress, physical function, medication use, and pain tolerance were examined in women and men with high versus low scores on spousal solicitousness. RESULTS: Among males only, high spousal solicitousness was associated with greater numerical ratings of pain and greater self-reported disability compared with patients with low solicitous spouses. Among females only, the high spousal solicitousness patients showed lower pain tolerance, greater pain-related interference, poorer performance on functional tasks (eg, timed walking, lifting, and carrying tasks), and greater use of opioid medications. In both women and men, spousal solicitousness was associated with higher scores on the MPI pain severity scale. DISCUSSION: These results extend previous findings demonstrating a relationship between spousal responses and patients' adjustment to pain; however, the pattern of these effects appears to be moderated by the sex of the patient. Implications for assessment and treatment of chronic pain are discussed.     

Pain tolerance as a predictor of outcome following multidisciplinary treatment for chronic pain: differential effects as a function of sex

Sex-related differences in the experience of clinical and experimental pain have been widely reported. Females are at elevated risk for developing several chronic pain conditions and women demonstrate greater sensitivity to noxious stimulation in the laboratory. However, relationships between responses to experimental noxious stimuli and the experience of clinical pain have not been well characterized. One previous study of healthy adults indicated that pain threshold and tolerance were associated with clinical pain among women but not men (i.e. females with lower pain threshold and tolerance reported more clinical pain). In the present investigation, relationships between pain tolerance and outcomes of treatment for chronic pain were evaluated in a sex-dependent manner. Ischemic pain tolerance was assessed prior to treatment in 171 chronic pain patients completing a pain management program. Outcomes were measured as changes in pain severity, affect, and pain-related disability. Over the course of treatment, women demonstrated greater improvement in pain-related disability while men showed more reduction in pain. Ischemic pain tolerance was related to outcome in a sex-specific fashion. Women with higher pain tolerances showed greater improvement in pain, more reduction in pain-related interference, and more increases in activity level than women with lower pain tolerances. In contrast, pain tolerance was not associated with positive treatment outcomes among men. These results indicate that experimental pain responses may be most clinically relevant for women, and that sex differences may exist in the determinants of pain-treatment outcomes.     

Sex Differences in Negative Emotional Responses to Chronic Pain

We proposed a sequential model of pain processing with pain intensity as stage 1, pain unpleasantness as stage 2, pain-related emotions (depression, anxiety, frustration, anger, fear) as stage 3, and overt behavioral expression of pain as stage 4. We tested hypotheses about relationships between sex and the first 3 stages of pain processing by conducting simultaneous regression analysis using LISREL-8 with data collected from 967 women and 680 men with chronic pain. We found the following results: (1) women reported higher pain-related frustration and fear; (2) frustration related most highly to pain intensity among women, as compared with anxiety and depression among men; (3) depression and frustration related most highly to usual and highest pain unpleasantness among women, as compared with frustration among men; and (4) contrary to expectations, pain-related emotions were more strongly related to pain for men. Consistent with the sequential model of pain processing, emotional response to pain was more closely related to pain unpleasantness than to pain intensity across sex. Anxiety and frustration were the emotions most highly related to pain. The current results highlight sex differences in the experience of chronic pain and the importance of assessing a range of emotions in patients with pain.     

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.     

Pain-related anxiety influences pain perception differently in men and women: A quantitative sensory test across thermal pain modalities

The sexes differ with respect to perception of experimental pain. Anxiety influences pain perception more in men than in women; however, there lacks research exploring which anxiety constructs influence pain perception differentially between men and women. Furthermore, research examining whether depression is associated with pain perception differently between the sexes remains scant. The present investigation was designed to examine how trait anxiety, pain-related anxiety constructs (ie, fear of pain, pain-related anxiety, anxiety sensitivity), and depression are associated with pain perception between the sexes. A total of 95 nonclinical participants (55% women) completed measures assessing the constructs of interest and participated in quantitative sensory testing using heat and cold stimuli administered by a Medoc Pathway Pain and Sensory Evaluation System. The findings suggest that pain-related anxiety constructs, but not trait anxiety, are associated with pain perception. Furthermore, these constructs are associated with pain intensity ratings in men and pain tolerance levels in women. This contrasts with previous research suggesting that anxiety influences pain perception mostly or uniquely in men. Depression was not systematically associated with pain perception in either sex. Systematic relationships were not identified that allow conclusions regarding how fear of pain, pain-related anxiety, and anxiety sensitivity may contribute to pain perception differentially in men and women; however, anxiety sensitivity was associated with increased pain tolerance, a novel finding needing further examination. The results provide directions for future research and clinical endeavors and support that fear and anxiety are important features associated with hyperalgesia in both men and women.     

Psychological factors in pelvic/urogenital pain: the influence of site of pain versus sex

Chronic pelvic pain (CPP), a fairly common gynecological complaint in women, has been associated with multiple psychological sequelae, including depression and somatization. Previous work has compared these patients to gynecological controls and women with headache, but has failed to include male comparison groups with a comparable site of chronic pain. In order to test possible sex and pain site differences, the present study compared 22 women with CPP, 22 men with either penile or testicular pain, 22 women with low back pain and 28 men with low back pain referred for a psychological evaluation as part of multidisciplinary pain treatment. Depression, coping, pain intensity and interference were assessed. Two-way analyses of variance (sex by pain site) were conducted to determine if there were group differences on demographic variables and medical history. Pain duration, age, and pain severity differed among the groups and were entered as covariates in hierarchical regression analyses designed to identify predictors of adjustment and pain coping. Sex and pain site did not contribute independently to the prediction of depressive symptoms. Pain site predicted physical functioning with low back pain patients reporting greater pain-related interference. Similar findings were demonstrated for coping. A variety of pain-coping strategies, including catastrophizing, were more frequently utilized by low back pain patients, regardless of sex. In the present study, pain severity and pain site explained more variance in depressive symptoms, physical functioning, and pain-coping than sex.     

Differential relationships between anxiety and treatment-associated pain reduction among male and female chronic pain patients

OBJECTIVES: Clinical, epidemiological, and laboratory-based studies have all suggested that female sex and elevated anxiety are associated with greater experience of pain. However, several recent reports have also indicated that sex may moderate the relationship between anxiety and responses to noxious stimuli, with anxiety more strongly related to pain among males. The present study examined whether anxiety differentially impacts outcomes for pain treatment among males and females. METHODS: Seventy-four chronic pain patients (34 males, 40 females) completed the Pain Anxiety Symptoms Scale and several other psychologic measures before undergoing a variety of treatment procedures including epidural steroids, trigger point injections, and participation in brief, cognitive-behaviorally oriented psychoeducational groups. Patients provided pre- and post-treatment ratings of pain for all interventions. RESULTS: Consistent with findings from previous investigations, the present study noted stronger relationships between baseline anxiety and pre-treatment pain severity among males relative to females. In addition, while lower levels of baseline anxiety were related to greater treatment-associated pain reduction among females, the reverse pattern emerged for males. These relationships persisted even after controlling for other psychologic factors such as depression, coping style, and hypervigilance. DISCUSSION: These findings suggest differential relationships between anxiety and pain relief as a function of sex. While we are unable to identify a mechanism for this effect, higher anxiety may have predicted more pain relief among males and less pain relief among females due to sex differences in coping strategies or placebo effects.     

Sex differences in the associations among psychological factors and pain report: a novel psychophysical study of patients with chronic low back pain.

Previous studies have consistently suggested that there are sex differences in pain report, but there is no consensus regarding sex differences in the associations among psychological factors and pain report. This cross-sectional study used a novel, clinically relevant, psychophysical pain-induction technique to examine sex differences between sensory and affective pain report and sex differences in the association of depression, pain related anxiety, and catastrophizing with pain report. Patients with chronic low back pain (N = 53) were recruited from an outpatient spine clinic, and those consenting completed self-report measures of pain-related anxiety, depression, pain catastrophizing, and pain. A measure of induced low back pain was obtained by having study participants perform a protocol on the MedXtrade mark Low-Back Exercise Apparatus. Our results indicated that no sex differences were detected in psychological factors and self-reported or induced low back pain. However, the relationships between pain related anxiety and self-report of low back pain (z = 2.51, P < .05) and between pain-related anxiety and induced low back pain (z = 3.00, P < .05) were significantly stronger in men than women. These findings suggest that anxiety was linked to self-reported and induced low back pain for men, but not for women. PERSPECTIVE: Results of this study suggest that pain-related anxiety has a stronger association with psychophysical and clinical reports of low back pain for men.     

Somatic focus/awareness: Relationship to negative affect and pain in chronic pain patients

Somatic focus refers to the tendency to notice and report physical symptoms, and has been investigated in relation to chronically painful conditions. This study investigated the relationship between somatic focus, as measured by the Pennebaker Inventory of Limbic Languidness (PILL), negative affect and pain. A secondary purpose of the present study was to examine sex differences in these relationships. Participants included 280 chronic pain patients (69.6% females, 88.9% Caucasian), who completed a battery of self‐report measures on somatic focus, pain, negative affect, coping, and dysfunction. Results for the overall sample revealed that the PILL shares considerable variance with measures of negative affect, particularly with the physiological components of anxiety and depression. When the results were analyzed separately for male and female patients, it was found that several components of negative affect and cognitive factors play a stronger role in predicting somatic focus among men compared to women. Additional analyses then examined whether somatic focus was predictive of male and female patients’ pain reports. Results indicated that somatic focus explained a small, but unique amount of variance in female patients’ pain reports, which differed from the relationship observed among male patients.     

Sex differences in perceived pain are affected by an anxious brain

Decades of research confirm that women have greater pain sensitivity than men. Women also show greater overall anxiety sensitivity than men. Given these differences, we hypothesized that sex differences in anxiety would explain sex differences in experienced pain and physiological responses to pain (at both spinal and cortical levels). By measuring subjective pain, state/trait anxiety, nociceptive flexion reflexes, and somatosensory evoked potentials (SEPs), it was possible to test the effects of anxiety on the processing of painful drives at different levels of the neuraxis while also documenting the role played by anxiety on sex differences in experienced pain. Results confirm that women are indeed more sensitive to pain than men. Importantly, this difference was accompanied by a significant sex difference in cortical activity (SEP amplitude) but not spinal nociceptive activity, suggesting that much of the sex difference in experienced pain is attributable to variations in thalamocortical processing and to ensuing changes in the appraisal of and/or emotional response to noxious insult. In support of this claim, we found that sex differences in cortical activity and subjective pain disappeared when trait anxiety was controlled for. This means that stable predispositions to respond with heightened apprehension contribute to baseline pain sensitivity differences between the sexes. These results indicate that the modulatory effect of affect on pain-related brain processes may explain why men and women experience painful shocks so differently. In our study, the mediating role of anxiety on sex differences in pain was tested and confirmed using path analysis.     

The immigrant patient having widespread pain. Clinical findings by physicians in Swedish primary care

AIM. Do the clinical findings explain the complaints of longstanding demonstrated widespread pain (DWP) in a group of immigrant patients, or not? SUBJECTS. Consecutive immigrant patients, on long-term sick leave, aged 18 - 45, at a primary healthcare centre in Stockholm, Sweden. METHODS. Interpreters were available. Two primary care physicians jointly, made a somatic status and diagnosed tender-structure locations (> or =3 tender-structure locations or less) and depression (yes or no), and assessed psychosocial stressors (little or much) and pain-related anxiety (yes or no). The patients pointed at their pain parts. This was transferred by one of the doctors to a pain drawing with 18 fields. Five or more fields were defined as DWP. Non-parametric tests were used to detect significant differences between the DWP and non-DWP groups. Cumulative frequencies of the following four categories of explanatory variables of DWP were counted: > or =3 tender-structure locations (could also include the other variables), much psychosocial stress (could include depression and pain-related anxiety), depression (could include pain-related anxiety), or pain-related anxiety alone. RESULTS. Many of the 49 men and 100 women, on average 38 years, spoke little or no Swedish. A fifth of the men (n = 10) and half (n = 56) of the women had DWP. These men often had much stress (p < 0.01) while the women had > or =3 tender-structure locations (p < 0.001). DWP among men was explained to 100% by: > or =3 tender-structure locations (30%), much psychosocial stress (60%), or depression alone (10%). DWP among the women was explained to 96 cum. % by: > or =3 tender-structure locations (59%), much psychosocial stress (25%), or pain-related anxiety alone (13%). CONCLUSION. Demonstrated widespread pain was nearly always explained by clinical findings, and especially by numerous tender-structure locations in women. There is a need for more studies among men.     

Behavioral dimensions of adjustment in persons with chronic pain: pain-related anxiety and acceptance

Through empirical methods we now characterize patients with chronic pain as either dysfunctional, interpersonally distressed, or adaptive copers. Studying factors that differentiate these groups may reveal the behavioral processes that determine adjustment to pain. Subjects for this study were 190 patients referred for treatment of chronic pain. They were classified as dysfunctional (n = 41), interpersonally distressed (n = 28) or adaptive copers (n = 59) based on the Multidimensional Pain Inventory (Kerns, R.D., Turk, D.C. and Rudy, T.E., The West Haven-Yale Multidimensional Pain Inventory (WHYMPI), Pain, 23 (1985) 345-356) and compared on measures of pain-related anxiety and pain acceptance. Our analyses showed that the dysfunctional group reported greater pain-related anxiety and less acceptance of pain than the other groups. Additional analyses, statistically controlling for pain severity and depression, showed that the patient subtypes continued to differ on pain-related anxiety and acceptance. Discriminant function analyses including pain-related anxiety and acceptance correctly classified 72.5% of dysfunctional and 90.9% of adaptive copers. Again, anxiety and acceptance contributed uniquely to classification independent of depression and pain intensity. Pain-related anxiety and acceptance of pain appear to be unique behavioral dimensions of adjustment to chronic pain. Decreasing anxiety and increasing acceptance may 'move' patients with chronic pain from the dysfunctional to the adaptive coper category.     

Cardiorespiratory fitness, physical activity level, and chronic pain: are men more affected than women?

OBJECTIVE: To evaluate the cardiorespiratory endurance (CRE) and physical activity level of patients with chronic pain compared with healthy subjects. DESIGN AND SUBJECTS: Cross-sectional study, with a consecutive sample of 55 patients with chronic pain (20 men, 35 women). Comparison of CRE and physical activity indices obtained in patients with data available in the literature for age-matched healthy subjects. SETTING: A multidisciplinary pain center in a city of more than 1,000,000 inhabitants. OUTCOME MEASURES: A physical working capacity index (PWC65%/kg) and physical activity level scores and subscores obtained with two questionnaires (the Baecke and the Five-City Project questionnaires). RESULTS: The physiological gender difference in CRE indices that characterizes healthy subjects was not observed in patients with chronic pain. When compared with values previously obtained in controls, male patients presented with a very significant 34% reduction in PWC65%/kg. The 17% reduction found in women hardly reached significance level. The Baecke total physical activity score was significantly higher in female than in male patients, a finding not observed in healthy controls. There was no significant difference between male and female patients in the Five-City Project total physical activity score expressed in kilocalories per day per kilogram (i.e., normalized for body weight), although data from the literature show that healthy men present with a significantly higher level of physical activity compared with healthy women. CONCLUSIONS: Data on CRE and the physical activity level of patients with chronic pain obtained in this study show that chronic pain may have a greater impact on male than female patients. Sociocultural factors are probably at the origin of this phenomenon.     

Coping or acceptance: what to do about chronic pain?

Research and treatment of chronic pain over the past 20 or more years have tended to focus on patient coping as the primary behavioral contribution to adjustment. The purpose of the present study was to compare a coping approach to chronic pain with a different behavioral approach referred to as acceptance of chronic pain. These approaches were compared in terms of their ability to predict distress and disability in a sample of patients seeking treatment for chronic pain. Subjects were 230 adults assessed at a university pain management center. All patients completed the coping strategies questionnaire and the chronic pain acceptance questionnaire among other standard measures. Results showed that coping variables were relatively weakly related to acceptance of pain and relatively unreliably related to pain adjustment variables. On the other hand, acceptance of chronic pain was associated with less pain, disability, depression and pain-related anxiety, higher daily uptime, and better work status. Regression analyses examined the independent contributions of coping and acceptance to key adjustment indicators in relation to chronic pain. Results from these analyses demonstrated that acceptance of pain repeatedly accounted for more variance than coping variables.     

The association between anxiety and chronic pain after whiplash injury: gender-specific effects

OBJECTIVE: There is increasing evidence to suggest that anxiety is related more strongly to chronic pain experience in men relative to women. The aim of the present study was to examine for the first time gender-specific associations between anxiety and chronic pain experience in men and women exposed to whiplash trauma. METHOD: One thousand seven hundred and nine people with whiplash (1349 women, 360 men) belonging to the Danish Society for Polio, Traffic, and Accident Victims completed a battery of questionnaires measuring demographic, psychologic, and pain-related factors (including frequency of painful episodes, level of pain interference, number of anatomic regions in which pain was felt, and the level of general disability). RESULTS: Anxiety was found to be positively related to the level of general disability to a significantly stronger magnitude in men compared with women. A trend difference in correlation magnitude was also found between men and women when comparing anxiety with pain frequency, with the magnitude of correlation being higher in men. DISCUSSION: The stronger association between anxiety and symptoms of whiplash trauma in men compared with women may be due to gender differences in the attribution of anxiety-related autonomic arousal as symptoms of whiplash injury. Alternatively, anxiety may differentially affect the willingness of men and women to report pain and other health indices. Anxiety is an important factor in understanding gender differences in whiplash-related symptoms such as chronic pain and disability, and requires further investigation.     

Sex differences in the long-term stability of forehead cold pressor pain.

The purpose of this study was to examine sex differences in the stability of experimental pain responding across time. Stability was assessed by using 2 forehead cold pressor applications separated by 9 months. Twenty-eight men and 20 women completed both Session 1 and Session 2. Repeated measures analysis of variance showed a main effect for Session on maximum pain level. Women reported significantly more pain at Session 2, whereas men showed no difference between sessions. There were no differences on pain report between men and women at Session 1. A significant Session by Sex interaction was associated with perceived chronic stress and trait anxiety levels. At Session 2 but not Session 1, women endorsed a significantly greater expectation than men to experience unpleasant aftereffects from the cold pressor task. Additional analysis showed that chronic stress and trait anxiety were significantly associated with sex-specific pain responding. We propose that the influence of a prior painful incident on an identical repeated painful experience differs between men and women. We speculate that this influence is related to sex differences in psychological mechanisms used to interpret painful stimuli within the context of remembered experiences. To our knowledge, this is the first report of sex differences in the long-term stability of an experimental laboratory pain stimulus, controlling for follicular phase of the female menstrual cycle. PERSPECTIVE: This study examines sex differences in the stability of experimental pain responding across a 9-month period. We speculate that psychological mechanisms influence one's interpretation of a prior painful incident and that this interpretation facilitates increased pain reporting in response to an identical repeated exposure, as was observed for women.     

Dispositional anxiety and the experience of pain: gender-specific effects.

AIM OF INVESTIGATION: Increased anxiety is believed to correlate with increased pain sensitivity in men and women. However, one laboratory-based study and one clinical-based study have offered evidence to suggest that the effect of anxiety in modulating pain sensitivity is specific to men only. The aim of the present study was to examine further whether anxiety differentially effects men and women's report of experimentally induced pain. METHODS: One hundred forty-four healthy university students (75 women, 69 men) were exposed to a contact heat pain procedure (ascending method of limits procedure, baseline temperature 30 degrees C, +/- 0.2 degrees C, rate of change 2.0 degrees C/s, cut-off limit 52 degrees C) and a cold pressor pain procedure (constant temperature +1 degrees C; +/-1 degrees C, cut-off limit 240 s). RESULTS: The results agreed with the previous two studies indicating a sex-specific effect of anxiety on pain report. Male participants scoring above the median on the Trait Anxiety Inventory reported significantly greater pain intensity, unpleasantness and showed lower pain tolerance compared to males scoring below the median on the cold pressor pain procedure, while no such differences in cold pressor pain report were found between high and low anxious women. No effect of anxiety was found on measures taken from the contact heat pain procedure, indicating that the sex-specific effect of anxiety on laboratory induced pain is dependent upon the method of stimulation used. CONCLUSION: Anxiety is an important factor when considering gender differences in pain perception and warrants further investigation.     

Cognitive complaints are associated with depression, fatigue, female sex, and pain catastrophizing in patients with chronic pain

OBJECTIVE: To examine the relation between demographic, pain-related, psychosocial, affective, and treatment factors and complaints of cognitive dysfunction among patients with chronic pain. DESIGN: Cross-sectional survey. SETTING: A university hospital outpatient multidisciplinary chronic pain program. PARTICIPANTS: Chronic pain patients (N=222; 135 women, 87 men) completed a battery of psychometric questionnaires as part of an initial evaluation on referral to the program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Cognitive impairment was assessed with items from the Brief Symptom Inventory; measures of depressive symptoms, pain intensity, posttraumatic stress disorder (PTSD), and pain catastrophizing were obtained from the Beck Depression Inventory (negative affect, negative self, somatic/physical function), McGill Pain Questionnaire, Modified Posttraumatic Chronic Pain Test, and Coping Strategies Questionnaire, respectively; and measures of subjective sleep disturbance, fatigue, opiate use, compensation/litigation status, pain location, and relevant demographic data were obtained from an open-ended questionnaire. RESULTS: Correlational analysis indicated that female sex, pain intensity, PTSD symptoms, depressive symptoms, catastrophizing, pain location (neck), and fatigue were all positively related to cognitive complaints. Simultaneous regression analysis showed that all factors combined accounted for 52% of the variance in self-report of cognitive difficulties and that 6 variables had a significant unique contribution to the report of cognitive complaints in the following order of importance: depression-negative affect (beta=.28, P <.05), fatigue (beta=.17, P <.05), depression-somatic/physical function (beta=.16, P <.05), depression-negative self (beta=.14, P =.05), pain catastrophizing (beta=.12, P =.08), and female sex (beta=.12, P <.05). CONCLUSIONS: Complaints of cognitive impairment among chronic pain patients appear to be associated with multiple factors, with particular attention to depressive symptoms, fatigue, and catastrophizing. Our results also suggest that women with chronic pain are particularly vulnerable to cognitive dysfunction.     

Sex differences in cortisol response to noxious stress

OBJECTIVES: Evidence has accumulated that men and women show different responses to noxious stimuli, with women exhibiting greater sensitivity to pain than men. Data concerning sex differences in cortisol response patterns have revealed inconsistent results so far. The purpose of the present study was to examine sex differences in subjective pain and cortisol response to a noxious stressor. METHODS: Seventy-six subjects (39 male and 37 female) were investigated by a modification of the cold pressor test that consisted of intermittent immersion of the hand into ice water (plunge test, PT). The PT was conducted twice, in consecutive trials, to guarantee a sufficient exposure to the noxious stressor for eliciting cortisol responses. In each trial, tolerance time and pain ratings visual analog scale (VAS) were assessed. Seven saliva samples (c1-c7) were collected to determine cortisol levels at baseline (c1-c2), directly before (c3) and 20 minutes after noxious stress (c4), and during recovery period (c5-c7). RESULTS: We found no significant sex differences in tolerance time in trial 1, but highly significant differences in tolerance time in trial 2, with higher tolerance times in men. No significant sex differences were found for the VAS ratings of pain intensity and unpleasantness in the 2 trials. In contrast, a significantly larger cortisol increase in men was observed compared with women. Analysis of covariance revealed that this result could not be attributed to sex differences in cortisol level at baseline and in tolerance time. DISCUSSION: The present study demonstrates that men show a larger cortisol response to a noxious stressor than women that is not attributable to sex differences in subjective pain. The conclusion of a causal relation between larger cortisol responses and higher pain tolerance thresholds in men is tempting but yet speculative.     

Sex similarities and differences in pain-related periaqueductal gray connectivity

This study investigated sex similarities and differences in pain-related functional connectivity in 60 healthy subjects. We used functional magnetic resonance imaging and psychophysiological interaction analysis to investigate how exposure to low vs high experimental pain modulates the functional connectivity of the periaqueductal gray (PAG). We found no sex differences in pain thresholds, and in both men and women, the PAG was more functionally connected with the somatosensory cortex, the supplemental motor area, cerebellum, and thalamus during high pain, consistent with anatomic predictions. Twenty-six men displayed a pain-induced increase in PAG functional connectivity with the amygdala caudate and putamen that was not observed in women. In an extensive literature search, we found that female animals have been largely overlooked when the connections between the PAG and the amygdala have been described, and that women are systematically understudied with regard to endogenous pain inhibition. Our results emphasize the importance of including both male and female subjects when studying basic mechanisms of pain processing, and point toward a possible sex difference in endogenous pain inhibition.