Sex Differences In Pain Perception Research Articles

Sex differences in delayed onset muscle soreness induced by fatigue and measured by different methods

BACKGROUND: Controversial outcomes from different methods for assessment of delayed onset muscle soreness (DOMS) in male and female may influence clinical decisions. AIM: In this study, we determine sex differences in pain perception and pain thresholds in a DOMS condition resultant of a fatigue protocol. METHOD: 11 male and 15 female healthy adults were submitted to an exercise fatigue protocol to induce DOMS in the quadriceps muscles. Pain perception was determined using a numeric pain rate scale (NRS) and pressure pain thresholds (PPT) were determined by mechanical pressure in the vastus lateralis (VL) and rectus femoris (RF) regions. Data were compared between methods and sexes at baseline, immediately after (0h), and 48 h after DOMS induction. RESULTS: Results showed normalized lower PPT and higher NRS outcomes after fatigue, without sex differences. Absolute values of PPT showed lower values in females comparing both time and sex (VL and RF, baseline p =0.002 and p =0.009; 0h p= 0.002 and p = 0.001; 48h p<0.001 and p<0.001) with a mean difference for females and males on 0h and 48h of from baseline VL 16,52% and 19.7%; -15.64% and -10.89%; RF 12.18% and 20.7%; -9.18% and -1.97%. No correlations were found between the number of repetitions of exercise nor the rate of perceived effort and DOMS outcomes. CONCLUSION: Men and women show similar DOMS when NRS and normalized PPT outcomes are considered. Absolute PPT values may lead to a confusing analysis of fatigue exercise-induced DOMS if merging both sexes in the sample.

Machine learning analysis predicts a person’s sex based on mechanical but not thermal pain thresholds

Sex differences in pain perception have been extensively studied, but precision medicine applications such as sex-specific pain pharmacology have barely progressed beyond proof-of-concept. A data set of pain thresholds to mechanical (blunt and punctate pressure) and thermal (heat and cold) stimuli applied to non-sensitized and sensitized (capsaicin, menthol) forearm skin of 69 male and 56 female healthy volunteers was analyzed for data structures contingent with the prior sex structure using unsupervised and supervised approaches. A working hypothesis that the relevance of sex differences could be approached via reversibility of the association, i.e., sex should be identifiable from pain thresholds, was verified with trained machine learning algorithms that could infer a person's sex in a 20% validation sample not seen to the algorithms during training, with balanced accuracy of up to 79%. This was only possible with thresholds for mechanical stimuli, but not for thermal stimuli or sensitization responses, which were not sufficient to train an algorithm that could assign sex better than by guessing or when trained with nonsense (permuted) information. This enabled the translation to the molecular level of nociceptive targets that convert mechanical but not thermal information into signals interpreted as pain, which could eventually be used for pharmacological precision medicine approaches to pain. By exploiting a key feature of machine learning, which allows for the recognition of data structures and the reduction of information to the minimum relevant, experimental human pain data could be characterized in a way that incorporates "non" logic that could be translated directly to the molecular pharmacological level, pointing toward sex-specific precision medicine for pain.

R2. Diverse Perceptions of Experimental Thermal Pain: Race-Related Differences between and within Sex

Sex-differences in pain assessment and treatment for Blacks and Whites is a public health concern. Black and White females typically report greater sensitivity to pain than men of either race. This pilot study investigated sex-differences in pain perception, in addition to determining if Black adults are more sensitive to experimental thermal pain and if greater unpleasantness is experienced at similar pain thresholds than White adults.

Sex differences in perceptual responses to experimental pain before and after an experimental fatiguing arm task

BackgroundThe incidence and prevalence of musculoskeletal disorders (MSDs) is about twice as high in women compared to men, and those of the neck/shoulder region are particularly high among women. Fatigue and responses towards pain are known risk factor for MSDs. However, women have been shown to be less fatigable than men, but more sensitive to experimental pain. From a general standpoint, sex differences in the relationships between the fatigue and pain pathways are poorly understood. This may be due to differences in how men and women conceptually define the sensations of fatigue and pain. The objective of this study was to compare physical and verbal descriptors of fatigue and pain between men and women undergoing an experimental protocol where fatigue and pain were manipulated.MethodsHealthy adult volunteers (14 men and 14 women) underwent experimental pain tests to identify pressure pain threshold (PPT) at biceps brachii (BIC), anterior deltoid (AD), and upper trapezius (UT) followed by the Short-form McGill Pain Questionnaire (SF-MPQ) and Pain Catastrophizing Scale (PCS) before and after a repetitive arm task performed at shoulder height until reaching a rating of neck/shoulder perceived exertion, using the Borg Category Ratio 10 (CR10), greater than 8/10. PPT and MPQ data were analyzed using repeated measures analyses of variance (ANOVA) (time × sex). Correlational analyses were used to investigate relationships between pain measures with time and fatigue.ResultsUT PPT was reduced following the fatiguing task (p ≤ 0.01). Men overall reported higher AD PPT levels compared to women (p ≤ 0.05). MPQ and PCS magnification scores were significantly higher after the fatiguing task (p ≤ 0.05), with no sex differences. Time to fatigue correlated with changes in AD PPT in men and with PCS scores in women.ConclusionsFindings suggest that mechanisms underlying the sensation of acute pain following a repetitive shoulder height task are closely linked with PPT changes in shoulder stabilizers (UT) irrespective of sex, and more so with physical pain responses in men and in attitudes towards pain in women. Sex differences in pain perception may contribute to a better understanding of sex-specific mechanisms underlying neck/shoulder MSDs.

Gender aspects of the pain syndrome

In recent years, the subject of sex differences in the pain experience attracts a growing interest. The epidemiological and clinical data indicate that women have increased risk of chronic pain, and according to some sources, even experience more intense pain. The hypothetical biological mechanisms underlying sex differences in pain perception consist in the modulating effects produced by sex hormones in relation to the neural substrate. This is confirmed by data on the distribution of gonadal hormones and their receptors in the areas of the peripheral and central nervous system that provide nociceptive transmission. The complexity of the estradiol and progesterone effects on pain sensitivity lies in the fact that, according to various data, both have pre-nociceptive and antinociceptive effects, and testosterone appears to be more characterized by antinociceptive properties. The lion’s share of researches demonstrates the effect of a clinical pain exacerbation during the menstrual cycle. There is irrefutable information about gender differences in responses to drug and non-drug pain treatment, although the results vary depending on a specific therapy and may depend on pain characteristics. Since the recommended dosage of a medication is often based on an “average” male weigh 70 kg, female patients may be facing the risk of increased therapeutic or adverse effects of a drug. The cause is in a higher average percentage of body fat, a lower mean body weight, which contributes to higher median drug concentrations compared with male patients. At present, the available evidence does not allow adapting the methods of pain syndrome treatment to a gender. However, such innovations are quite possible and desirable in the foreseeable future. Additional studies will be required to clarify the mechanisms that determine sex differences in pain responses in order to provide adequate pain relief, according to the patient’s needs.

Sleeping through anything: The effects of unpredictable disruptions on mouse sleep, healing, and affect.

Many aspects of the laboratory environment are not tailored to the needs of rodents, which may cause stress. Unpredictable stressors can cause ulcers, prolonged pituitary-adrenal activation, and anhedonia. Similarly, pain has been demonstrated to slow wound healing, and mice experiencing pain exhibit altered behavior. However it is unknown how husbandry, which occurs when the mice are inactive, and lack of analgesia, specifically in a punch biopsy procedure, effects animal physiology, behavior, and welfare, particularly as it relates to sleep fragmentation. We hypothesized that sleep fragmentation, induced by unpredictable husbandry and lack of pain management will slow wound healing. Two main treatments were tested in a factorial design in C57BL/6 mice of both sexes (64 mice total); 1) analgesia (carprofen and saline) and 2) sleep disruptions (random and predictable). Mice were singly housed in a non-invasive sleep monitoring apparatus on arrival (Day -4). Disruption treatments were applied from Day -3 to 2. All mice received a punch biopsy surgery (Day 0) with topical lidocaine gel and their analgesic treatment prior to recovery, and on Days 1 and 2. Nesting behavior was assessed daily and a sugar cereal consumption test, as a measure of anhedonia, was conducted on Days -1 to 2. On Day 3, mice were euthanized and wound tissue and adrenal glands were collected. We found that the disruption predictability had no effect on mouse sleep, wound healing, or adrenal cortex:medulla ratio. It’s possible that the disruption period was not long enough to induce chronic stress. However, male mice who received analgesia slept more than their female counterparts; this may be related to sex differences in pain perception. Overall, it does not appear that the predictability of disturbance effects sleep fragmentation or stress responses, indicating that husbandry activities do not need to occur at set predictable times to improve welfare.

Digit ratio (2D:4D) and postoperative pain perception

BackgroundsIt has not been established whether sex differences in pain perception are influenced by prenatal sex hormones. Digit ratio as an indicator of prenatal hormone exposure can be used as a simple measure of the influence of prenatal hormones on pain sensitivity or perception in adulthood. ObjectiveThe aim of this study was to determine a correlation between the 2D:4D ratio and pain perception in the postoperative period after rhinoplasty. MethodA prospective cohort study of 100 patients (50 women of the mean age of 30.74±8.09years and 50 men of the mean age of 30.98±10.86years) who underwent posttraumatic rhinoplasty due to the nose trauma in Plastic, Reconstructive and Aesthetic Surgery Clinic. The following measurements were taken the day before a surgery: body height, waist and hip circumference, II and IV digits' lengths and body weight. All subjects filled in a questionnaire including 0–10-point VAS scales to assess postoperative pain 1h after an operation (AO), 6h AO, 12h AO, 24h AO and 48h AO. ResultsWomen with low 2D:4D reported significantly more pain 1h after an operation than women with high 2D:4D. Similar correlation was observed for low 2D:4D in women 48h AO. In men, low 2D:4D was associated with lower postoperative pain 12h AO (p=0.029). ConclusionIn conclusion, we showed that low 2D:4D in women was associated with high postoperative pain, and low right 2D:4D in men was associated with low postoperative pain. This may suggest that intrauterine estrogen exposure makes women more resistant to pain.

Non-invasive anaesthetic methods for dermatological laser procedures: a systematic review.

Pain is a common side-effect of dermatological laser procedures. Non-invasive anaesthetic drugs and anaesthetic procedures can be used to provide pain relief and increase patient satisfaction and treatment efficacy. However, it remains unclear which method provides the best pain relief. The objective of this systematic review was therefore to assess the efficacy and safety of non-invasive anaesthetic methods during dermatological laser procedures. A systematic literature search was conducted. Randomized and non-randomized controlled clinical trials (RCTs and CCTs) were included. Two authors independently assessed study eligibility, extracted data and assessed the risk of bias. The quality of evidence was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Twenty RCTs and 12 CCTs were included, involving nine different laser indications: hair removal (n = 9), resurfacing/rejuvenation (n = 5), port wine stains (n = 8), leg telangiectasia (n = 3), facial telangiectasia (n = 2), tattoo removal (n = 2), naevus of Ota (n = 1), solar lentigines (n = 1) and HPV lesions (n = 1). The non-invasive anaesthetic methods (i.e. topical anaesthetic drugs, skin cooling, and pneumatic skin flattening [PSF]), types of lasers, laser settings, application time, and types of pain scales varied widely among the included studies. All of the studies had an unclear or high risk of bias, and the overall quality of evidence was rated as low. In general, active non-invasive anaesthetic methods seemed to provide favourable results compared to placebo or no anaesthesia, and topical anaesthetic drugs and PSF seemed to result in a better pain reduction than skin cooling. However, the current evidence is insufficient to provide recommendations for daily clinical practice. There is a need for more high-quality (head-to-head) RCTs. Future studies should also evaluate sex differences in pain perception, have uniformity with regard to validated pain measurement scales and address clinically significant differences in pain reduction besides statistically significant differences.

Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc.

Sex Differences in Elderly Patients Using Patient Controlled Analgesia in the Postoperative Period: A Retrospective Database Analysis

Summary Background Sex differences in pain perception exist in humans. This study aimed to search whether sex differences also existed in patient controlled analgesia (PCA) among elderly populations. Methods Patients’ information was retrieved from a quality-insurance database from a period of 2 years. Demographic characters, types of PCA mode, consumptions of PCA drugs on postoperative Day 1, all PCA-related complications, visual analogue scale in bed rest, daily activities, and coughing, surgical sites, American Society of Anesthesiologists physical status, and satisfaction to PCA were all analyzed. Results A total of 1441 women (71.6 ± 8.4 years) and 730 men (70.9 ± 7.7 years) were analyzed. Elderly women had higher incidences of nausea, vomiting, vertigo, inappropriate sensory and motor blockages, as well experiencing more pain in bed rest and daily activities. Elderly men had more pain experience while coughing but had higher satisfactions to PCA. Conclusion Several important sex differences existed in the elderly patients when utilizing PCA as pain management. More concern should be drawn to these differences to minimize PCA-related complications and to avoid the potential hazard of PCA in vulnerable elderly patients. Generalization of this application in other constitutions requires further studies.

Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease.

Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland-Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease.

Gender Differences Among Military Combatants: Does Social Support, Ostracism, and Pain Perception Influence Psychological Health?

The literature on gender differences related to psychological health among in-theater service members who are deployed in a combatant role is limited. Much focuses on retrospective reports of service members who have returned from deployment. Potential key factors that contribute to gender differences in psychological health among combatants are found in literature across several topic areas, but integration of findings across disciplines is lacking. A growing body of literature on gender differences related to psychological health of postdeployment military populations suggests males and females respond differently to perceived levels of social support pre-and postdeployment. One study on service members who were deployed suggested no significant gender differences related to reported psychological health symptoms, but did appear to find significant gender differences related to reported perception of unit morale. In another related area, research explores how ostracism impacts physical and psychological health of individuals and organizations, and can result in perceptions of physical pain, although research on gender differences related to the impact of ostracism is scarce. Research has also begun to focus on sex differences in pain responses, and has identified multiple biopsychosocial, genetic, and hormonal factors that may contribute as potential underlying mechanisms. In this brief review, we focus on and begin to integrate relevant findings related to the psychological health of females in combat roles, gender differences in the impact of perception of social support on psychological health, the psychological and physical impact of ostracism on individuals and organizations, and the current literature on sex differences in pain perception. We conclude with a synthesis and discussion of research gaps identified through this review, implications for clinical practice, and potential future research directions. In conclusion, there appear to be gender differences related to the presence or absence of social support, the impact of ostracism, and the perception of pain. These differences may play a critical role in the psychological health of female combatants. More research on this topic is needed.

17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception

Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

Modulation of imidazoline I2 binding sites by CR4056 relieves postoperative hyperalgesia in male and female rats.

BACKGROUND AND PURPOSECR4056 is a novel imidazoline-2 (I2) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.EXPERIMENTAL APPROACHBy measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.KEY RESULTSOral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2/α2-adrenoceptor antagonist idazoxan, were partially reduced (∼30%; P < 0.05) by the selective α2-adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1/α2-adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine.CONCLUSIONS AND IMPLICATIONSCR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. CR4056 has successfully completed Phase I studies for tolerability and pharmacokinetics in healthy volunteers, and is currently entering the first proof-of-concept study in patients.

Sex Differences in the Neural Representation of Pain Unpleasantness

Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. PerspectiveThis article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain.

Intramuscular injections in newborns: analgesic treatment and sex-linked response

Aim: To compare the analgesic effect of three treatments to relieve the pain produced by intramuscular injections (IMI) in term newborns, and to assess sex-linked differences in their response to pain. Material and methods: We studied 62 babies. Each baby received antibiotic IMIs for clinical aims. During each IMI, one of the following analgesic treatments was utilized: oral 33% glucose (OG), sensorial saturation (SS), or topic anesthetic cream (TAC). SS is a validated analgesic method, based on the combination of three stimulations (tactile, acoustic and gustative). During the IMI, pain level was assessed with the use of the DAN scale, a validated neonatal pain scale. All babies who received three distinct analgesic procedures for three distinct IMIs were enrolled. Mean pain scores of the three analgesic treatment groups were compared. We then compared mean pain scores of females vs males in the whole cohort and within each treatment group. Results: The 95% Confidence Intervals of pain scores were 5.6–6.5 for TAC, 1.4–2.3 for OG and 0.6–1.2 for SS: when treated with TAC, babies’ pain scores were significantly higher than with OG or SS (p <0.0001); when treated with OG, babies’ pain scores were higher than SS (p = 0.002). Females’ mean pain score was significantly higher than males’ mean pain score: (95% CI: 2.9–4.1 vs 2.0–3.1; p = 0.01). OG and SS produced significantly higher mean DAN scores in females than in males. Also in the TAC group females’ mean DAN scores were higher than males, though this last difference was not statistically significant. Conclusion: This is the first study to show the effectiveness of nonpharmacologic analgesia in relieving IMI pain. It is also the first study to clearly show that the sex differences in pain perception are present since birth.

A systematic literature review of 10 years of research on sex/gender and pain perception – Part 2: Do biopsychosocial factors alter pain sensitivity differently in women and men?

This systematic review summarizes the results of 10years of laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian to access multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The second set of results presented in this review (129 articles) examined various biopsychosocial factors that may contribute to differences in pain sensitivity between healthy women and men. The results revealed that the involvement of hormonal and physiological factors is either inconsistent or absent. Some studies suggest that temporal summation, allodynia, and secondary hyperalgesia may be more pronounced in women than in men. The evidence to support less efficient endogenous pain inhibitory systems in women is mixed and does not necessarily apply to all pain modalities. With regard to psychological factors, depression may not mediate sex differences in pain perception, while the role of anxiety is ambiguous. Cognitive and social factors appear to partly explain some sex-related differences. Finally, past individual history may be influential in female pain responses. However, these conclusions must be treated with much circumspection for various methodological reasons. Furthermore, some factors/mechanisms remain understudied in the field. There is also a need to assess and improve the ecological validity of findings from laboratory studies on healthy subjects, and perhaps a change of paradigm needs to be considered at this point in time to better understand the factors that influence the experience of women and men who suffer from acute or chronic pain.

A systematic literature review of 10 years of research on sex/gender and experimental pain perception – Part 1: Are there really differences between women and men?

The purpose of this systematic review was to summarize and critically appraise the results of 10years of human laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian and conducted in multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The first set of results (122 articles), which is presented in this paper, examined sex difference in the perception of laboratory-induced thermal, pressure, ischemic, muscle, electrical, chemical, and visceral pain in healthy subjects. This review suggests that females (F) and males (M) have comparable thresholds for cold and ischemic pain, while pressure pain thresholds are lower in F than M. There is strong evidence that F tolerate less thermal (heat, cold) and pressure pain than M but it is not the case for tolerance to ischemic pain, which is comparable in both sexes. The majority of the studies that measured pain intensity and unpleasantness showed no sex difference in many pain modalities. In summary, 10years of laboratory research have not been successful in producing a clear and consistent pattern of sex differences in human pain sensitivity, even with the use of deep, tonic, long-lasting stimuli, which are known to better mimic clinical pain. Whether laboratory studies in healthy subjects are the best paradigm to investigate sex differences in pain perception is open to question and should be discussed with a view to enhancing the clinical relevance of these experiments and developing new research avenues.

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.

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. The initial search identified 718 titles and abstracts. Seventeen studies were included in the final stage and data regarding age and gender of participants, methodology and outcome measurements were extracted and analyzed. The majority of studies using pain report as the outcome found significantly more efficient DNIC in males than females (mean female/male ratio = 0.54). Studies evaluating pain thresholds and nociceptive flexion reflex indicated the opposite when simply averaged across studies; however, weighted analyses of threshold found more efficient DNIC in males. Gender differences in DNIC effect depend on both the experimental methodology and the modes of measurement of the effect.