Sex differences in functional brain activation during noxious visceral stimulation in rats

Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [¹⁴C]-iodoantipyrine was injected intravenously in awake, non-restrained female rats during 60- or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of three-dimensionally reconstructed brains. Sex differences were addressed by comparing the current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional–arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans.     

Sex differences in adolescent chronic pain and pain-related coping

Sex differences exist in pain and the strategies used to cope with pain. Although it is has been proposed that such differences become apparent around puberty, somewhat surprisingly very little research has specifically investigated sex as a moderator of pain within adolescents. The primary aim of the current study was to investigate sex differences in pain and coping within a group of 46 male and 115 female adolescent chronic pain sufferers. All were aged between 11 and 19 years and had been referred to the Pain Management Unit at the Royal National Hospital for Rheumatic Diseases, United Kingdom. Patients completed a battery of measures including pain experiences and a pain coping questionnaire. No sex differences were found in pain chronicity, although males and females did differ in self-reported pain experiences (females reported higher pain). Sex differences were also found in coping behaviours. Females used more social support, positive statements and internalizing/catastrophizing, whereas males reported engaging in more behavioural distraction. Of these strategies internalizing/catastrophizing was found to mediate the relationship between sex and pain. This suggests that not only do sex differences exist in the pain experiences and pain-coping strategies of adolescents with chronic pain, but that internalizing/catastrophizing may be an important mechanism in understanding such differences. More research examining potential sex differences in children and adolescents is recommended.     

Depression in chronic pain patients: relation to pain, activity, and sex differences

Depression is commonly reported among chronic pain patients and receiving increased attention from clinicians and researchers. There is, however, little empirical evidence concerning variables that differentiate depressed from non-depressed chronic pain patients, and whether depression is related to factors such as gender, pain report, and activity. As part of a study to address these questions, 63 chronic pain patients completed daily diaries of activity, pain levels, and medication intake, and completed questionnaires and interviews assessing depression, medical history, and demographic variables. Male and female depressed and non-depressed chronic pain patients did not differ on demographic and medical history data, but sex differences were found in patterns of the relationships of depression, activity, and pain. For women, depression was closely related to pain report, whereas for men depression was more strongly related to impairment of activity. Pain report was related only minimally to activity for male and female patients. Implications of the results of behavioral research on depression in chronic pain patients are discussed. Researchers are urged to carefully consider sex differences in future research with chronic pain patients.     

Widespread brain activity during an abdominal task markedly reduced after pain physiology education: fMRI evaluation of a single patient with chronic low back pain

The way people with chronic low back pain think about pain can affect the way they move. This case report concerns a patient with chronic disabling low back pain who underwent functional magnetic resonance imaging scans during performance of a voluntary trunk muscle task under three conditions: directly after training in the task and, after one week of practice, before and after a 2.5 hour pain physiology education session. Before education there was widespread brain activity during performance of the task, including activity in cortical regions known to be involved in pain, although the task was not painful. After education widespread activity was absent so that there was no brain activation outside of the primary somatosensory cortex. The results suggest that pain physiology education markedly altered brain activity during performance of the task. The data offer a possible mechanism for difficulty in acquisition of trunk muscle training in people with pain and suggest that the change in activity associated with education may reflect reduced threat value of the task.     

Sex and age differences in coping styles among children with chronic pain

The purpose of this study was to examine sex and age differences in coping strategies among pediatric patients with chronic pain. Sex differences are reported in the adult pain and coping literatures, but little attention has been given to possible distinctions in coping styles in the pediatric chronic pain population. Investigating pain coping skills at an early age may provide clinicians with a better understanding of the evolution of characteristic coping styles and identify areas for intervention. Pain intensity (Visual Analog Scale), pain coping strategies (Pain Coping Questionnaire), and coping efficacy were assessed in children (ages 8-12 years) and adolescents (ages 13-18 years), presenting to a pediatric chronic pain clinic (n=272). Significant sex differences in coping strategies were found. After controlling for pain intensity, girls used social support seeking more than boys, while boys used more behavioral distraction techniques. Adolescents engaged in more positive self-statements (a cognitive strategy) than children. Both boys and girls showed a trend toward pain coping efficacy being negatively correlated with average pain intensity. For girls, pain coping efficacy was also significantly negatively correlated with internalizing/catastrophizing. However, no sex or age differences in coping efficacy were found. This study demonstrates the early emergence of sex- and aged-based preferences in coping strategies among children and adolescents with chronic pain. The findings establish a basis for further research on early social influences in the development of pain coping styles in males and females. Implications for further clinical research in this area are discussed.     

Sex differences in experimental and clinical pain sensitivity for patients with shoulder pain

Previous research demonstrates that men and women differ in the way that they perceive and process pain. Much of this work has been done in healthy adults with a lack of consensus in clinical pain populations. The purpose of this study was to investigate how men and women with shoulder pain differ in their experience of experimental and clinical pain and whether psychological processes differentially affect these responses. Fifty‐nine consecutive subjects (24 women, 35 men) seeking operative treatment for shoulder pain were enrolled in this study. Subjects completed self report questionnaires to assess clinical pain, catastrophizing, anxiety and depression and underwent a series of experimental pain tests consisting of pressure pain, thermal pain (threshold and tolerance), and thermal temporal summation. Results indicated that women experienced greater clinical pain and enhanced sensitivity to pressure pain. Age did not affect the observed sex differences. There were no sex differences in psychological association with experimental and clinical pain in this cohort. The relationship between clinical and experimental pressure pain was stronger in women as compared to men. These findings offer insight into the interactions between biological and psychosocial influences of pain and how these interactions vary by sex.     

Characteristics of atherosclerotic lesion of the abdominal aorta and its unpaired visceral branches in patients with chronic abdominal ischemia

AIM: To study characteristics of echocardiographically detectable structural changes of the abdominal major arteries due to atherosclerosis with consideration of clinical symptoms. MATERIAL AND METHODS: 174 participants of the study had chronic abdominal ischemia (CAI). 20 healthy individuals served as control. The analysis was made of the data obtained at clinical laboratory tests, endoscopic and x-ray examinations, ultrasound investigation (USI) of the abdominal organs, USI of abdominal arteries in B-mode, transabdominal USI of the vertebral column. RESULTS: Echographically detectable signs of atherosclerotic affection of abdominal arteries in CAI patients are the following: increased lumen of the abdominal aorta (AA), unpaired visceral arteries in proximal and/or distal parts, relative narrowing of unpaired visceral arteries at the site of their origin from the aorta, lengthening of the abdominal aorta, S-shape configuration of the aorta on the longitudinal sections, thick aortal wall, unpaired visceral arteries, uneven thickness of the wall, plane foci of high echogenicity on the internal surface of the vascular wall, single or multiple hyperechogenic foci responsible for partial obstruction in the vessels. CONCLUSION: Degenerative changes of the intervertebral disks and corresponding atherosclerotic changes of the abdominal aorta, atherosclerotic affection of the unpaired visceral arteries may cause abdominal pain syndrome in CAI patients.     

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.     

Anatomical connections between brain areas activated during rectal distension in healthy volunteers: A visceral pain network

Diffusion Tensor Imaging (DTI) is a promising new imaging method allowing in vivo mapping of anatomical connections in the living human brain. We combined DTI with functional magnetic resonance imaging (fMRI) to investigate the anatomical relationships between areas involved in visceral sensations in humans. Non‐painful and moderately painful rectal distensions were performed in 11 healthy women (38.4 ± 3.1 years). fMRI was used to analyse the changes in brain activity during both types of distension. Then, DTI was applied for tracking fibers between the main activated regions. Non‐painful distension bilaterally activated the PreFrontal Cortex (PFC), the Anterior Cingulate Cortex (ACC) and the right insula. Painful distension bilaterally activated the primary (S1) and secondary (S2) somatosensory cortices, the motor cortex, the frontal inferior gyrus, the thalamus, the insula, the striatum and the cerebellum. DTI revealed direct connections between insula, and the four areas more frequently activated in this study, i.e. ACC, thalamus, S1, S2 and PFC. The combined use of fMRI and DTI in healthy subjects during rectal distension revealed a neural network of visceral sensory perception involving the insula, thalamus, somatosensory cortices, ACC and PFC.     

Sex differences in lumbopelvic movement patterns during hip medial rotation in people with chronic low back pain

Hoffman SL, Johnson MB, Zou D, Van Dillen LR. Sex differences in lumbopelvic movement patterns during hip medial rotation in people with chronic low back pain.

Objective

To examine sex differences in lumbopelvic motion and symptom behavior during hip medial rotation in people with low back pain (LBP). We hypothesized that men would demonstrate greater and earlier lumbopelvic motion and would be more likely to report increased symptoms compared with women.

Design

Cross-sectional observational study.

Setting

University musculoskeletal analysis laboratory.

Participants

Persons with chronic LBP (N=59; 30 men, 29 women) were recruited from the community and a university-based physical therapy clinic.

Interventions

Not applicable.

Main Outcome Measures

Lumbopelvic rotation range of motion, amount of hip rotation completed before the start of lumbopelvic motion, and provocation of LBP symptoms during the test of prone hip medial rotation were measured.

Results

Men demonstrated significantly more lumbopelvic rotation (men, 10.0°±5.1°; women, 4.5°±3.9°; P<.001) and completed less hip rotation before the start of lumbopelvic motion (men, 5.4°±3.8°; women, 16.0°±13.2°; P<.001) compared with women. Additionally, a significantly greater percentage of men (60.0%) than women (34.5%; P=.050) reported increased symptoms with hip medial rotation.

Conclusions

Men could be at greater risk than women for experiencing LBP symptoms related to hip medial rotation as a result of greater and earlier lumbopelvic motion.     

Physical and emotional functioning of adult patients with chronic abdominal pain: comparison with patients with chronic back pain.

Adults with chronic abdominal pain remain a poorly defined population, despite the debilitation and depression associated with this therapeutically challenging condition. This study compared patients with chronic abdominal pain with an empirically well-known group of patients with chronic pain (back pain) to investigate similarities and differences in their physical and mental functioning. This retrospective, cross-sectional study included 136 patients with abdominal pain and 364 patients with back pain seen in a comprehensive pain rehabilitation center. Patients' functioning was assessed with the Short Form-36 Health Survey, Multidimensional Pain Inventory, Center for Epidemiological Studies-Depression scale, and Coping Strategies Questionnaire-Catastrophizing subscale. Both the abdominal and back pain patients reported long-standing and severe pain, numerous surgery procedures, poor functioning, and high prevalence of depression. When age, education, and marital status were controlled for, analyses showed that although patients with abdominal pain reported significantly better physical functioning than patients with back pain (P < .001), their overall health perception was significantly poorer (P < .001). Although less prevalent, it is clear that patients with chronic abdominal pain exhibit poor functioning and prevalence of depression that are comparable to patients with chronic back pain. This study also suggests distinct characteristics that are vital to consider for effective treatment of this chronic pain population. PERSPECTIVE: As a result of being an overlooked and poorly defined population, adults with chronic abdominal pain might not receive adequate pain management treatment. Learning more about the physical and emotional functioning of patients with long-standing abdominal pain can increase recognition of the needs of and improve treatment for this population.     

Sex differences in endogenous pain modulation by distracting and painful conditioning stimulation

Sex differences in endogenous pain modulation were tested in healthy volunteers (32 men, 30 women). Painful contact heat stimuli were delivered to the right leg alone, and then in combination with various electrical conditioning stimuli delivered to the left forearm. Four conditioning protocols were applied to each subject in separate sessions: mild, non-painful (control); distracting; stressful-yet-non-painful; strongly painful. Thermal stimuli were rated on visual analog scales for pain intensity (INT) and unpleasantness (UNP). Distracting and painful conditioning stimuli significantly reduced heat pain INT and UNP ratings for both sexes, with significantly larger distraction effects on INT ratings for men than women (p=0.004). No sex differences in pain-evoked hypoalgesia were detected (p>0.05). The stress protocol did not consistently reduce heat pain ratings, possibly because the protocol was not sufficiently stressful to activate endogenous modulatory systems. Regression analysis revealed that the magnitude of pain-evoked hypoalgesia was predicted by the perceived distraction (p=0.003) and stress (p=0.04) produced by the painful conditioning stimulation, providing evidence that distraction and stress contribute to pain-evoked hypoalgesia. However, the contribution of stress to pain-evoked hypoalgesia differed by sex (p=0.02), with greater perceived stress associated with greater hypoalgesia in men and the opposite trend in women, suggesting sex differences in the mechanisms underlying pain-evoked hypoalgesia. This study provides indirect evidence that multiple neural mechanisms are involved in endogenous pain modulation and suggests that sex-specific aspects of these systems may contribute to greater pain sensitivity and higher prevalence of many chronic pain conditions among women.     

Thalamic field potentials during deep brain stimulation of periventricular gray in chronic pain

Stimulation of the central gray matter areas has been used for the treatment of chronic pain for decades. To better understand the mechanism of action of such treatment we studied the effects of stimulation of the periventricular gray (PVG) on the sensory thalamus in two patients with chronic central pain. In each case, two electrodes were implanted in the PVG (Medtronic 3389) and the ventroposterolateral thalamic nucleus (Medtronic 3387), respectively, under guidance of CT/MRI image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-25 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency FPs at 0.2-0.4 Hz closely associated with the pain. During 5-25 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz) however, there was no reduction in the FPs and no pain suppression. We have found an interesting correlation between thalamic activity and chronic pain. This curious low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation.     

Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation

The SF-36 is a well-validated health status instrument measuring eight different health concepts. One aim of this study was to compare health status as measured by SF-36 in subjects from the general population with no chronic pain (NCP), chronic regional pain (CRP), and chronic widespread pain (CWP). A second aim was to assess if SF-36 could reflect changes in pain status over time. A third aim was to study if health status at baseline, measured by SF-36, could predict pain status 3 years later. The study was designed as a 3-year follow up with a postal questionnaire, including the SF-36 health survey, to 2357 subjects from the general population aged 20-74 years. The results were controlled for age, sex, co-morbidity, and socio-economic status. At baseline, all eight health concepts of SF-36 discriminated between subgroups with NCP, CRP and CWP. Changes in SF-36 over the 3-year follow up time coincided with improvement or deterioration of pain status. Baseline SF-36 scores predicted pain outcome 3 years later. These results support that both physical and mental aspects of health status as measured by SF-36 are affected by the burden of musculoskeletal pain, are sensitive to changes in pain status, and also predict the further development of pain.     

A typology of pain coping strategies in pediatric patients with chronic abdominal pain

This study aimed to identify clinically meaningful profiles of pain coping strategies used by youth with chronic abdominal pain (CAP). Participants (n=699) were pediatric patients (ages 8-18 years) and their parents. Patients completed the Pain Response Inventory (PRI) and measures of somatic and depressive symptoms, disability, pain severity and pain efficacy, and perceived competence. Parents rated their children's pain severity and coping efficacy. Hierarchical cluster analysis based on the 13 PRI subscales identified pain coping profiles in Sample 1 (n=311) that replicated in Sample 2 (n=388). Evidence was found of external validity and distinctiveness of the profiles. The findings support a typology of pain coping that reflects the quality of patients' pain mastery efforts and interpersonal relationships associated with pain coping. Results are discussed in relation to developmental processes, attachment styles, and treatment implications.     

Distraction from chronic pain during a pain-inducing activity is associated with greater post-activity pain

The aim of this study was to investigate the effects of distraction from pain during and after a pain-inducing lifting task in a sample of chronic low back pain (CLBP) patients. Fifty-two CLBP patients (25 males, 27 females; mean age=46.30 years) performed a pain-inducing lifting task twice, once alone and once with a simultaneous cognitive distraction task. The results revealed that (1) distraction had no effect upon self-reported pain during the lifting task, (2) distraction had a paradoxical effect of more pain immediately after the lifting task, (3) both pain-related fear and pain catastrophizing did not moderate the effects of distraction on pain, but (4) catastrophic thinking about pain during the lifting task was related to more vigilance to pain and less engagement in the distracting task. Further investigation of the catastrophizing data showed that the effect of catastrophizing about pain during the lifting task on the cognitive distraction task was mediated by the amount of attention paid to pain. Clinical implications of these findings are discussed.     

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.     

Structural brain network characteristics in patients with episodic and chronic migraine

BackgroundMigraine is a primary headache disorder that can be classified into an episodic (EM) and a chronic form (CM). Network analysis within the graph-theoretical framework based on connectivity patterns provides an approach to observe large-scale structural integrity. We test the hypothesis that migraineurs are characterized by a segregated network.Methods19 healthy controls (HC), 17 EM patients and 12 CM patients were included. Cortical thickness and subcortical volumes were computed, and topology was analyzed using a graph theory analytical framework and network-based statistics. We further used support vector machines regression (SVR) to identify whether these network measures were able to predict clinical parameters.ResultsNetwork based statistics revealed significantly lower interregional connectivity strength between anatomical compartments including the fronto-temporal, parietal and visual areas in EM and CM when compared to HC. Higher assortativity was seen in both patients’ group, with higher modularity for CM and higher transitivity for EM compared to HC. For subcortical networks, higher assortativity and transitivity were observed for both patients’ group with higher modularity for CM. SVR revealed that network measures could robustly predict clinical parameters for migraineurs.ConclusionWe found global network disruption for EM and CM indicated by highly segregated network in migraine patients compared to HC. Higher modularity but lower clustering coefficient in CM is suggestive of more segregation in this group compared to EM. The presence of a segregated network could be a sign of maladaptive reorganization of headache related brain circuits, leading to migraine attacks or secondary alterations to pain.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01216-8.