Sex Flashcards
intro
Pain is modified by biological and psychosocial factors, therefore sex/gender differences should also play a role pain perception.
Sex differences in experimental pain
Pain thresholds smaller, pain endurance shorter and subjective pain stronger in females than males.
Riley et al. (1998)
meta-analysis of 21 studies in experimental pain threshold and pain tolerance.
The largest differences were for electrical and pressure stimulation: males showed higher thresholds than females. The mean effect size over different types of stimuli was 0.55 and 0.57 for pain threshold and pain tolerance, respectively.
Fillingim et al. (2009) analysed studies published after 1998, and confirmed the picture of greater pain sensitivity in females than males:
o pressure pain – 8 out 9 studies
o cold pain – greatest effect in pain tolerance
heat pain - >80% of studies confirming
Racine et al’ s review 1998-2008
Analysed 172 papers on sex differences in experimental pain after 1998.
No consistent differences in pain intensity or pain thresholds.
Pain tolerance was greater in males than females for cold (in 81% of studies), heat (80%), and pressure pain (86%)
Experimental allodynia, induced with capsaicin - Some evidence of a more widespread cutaneous region giving allodynia in females than males (large variability in methods, small number of studies)
Diffuse noxious inhibitory control (DNIC) refers to suppression of pain by other painful event occurring in a remote part of the body – involves brain-stem control centres and a final inhibitory synapse on WDR neurons in the spinal cord
Popescu et al. (2010)
reviewed 17 studies comparing effects of DNIC in males and females
o males showed stronger DNIC in pain intensity in most studies
o less clear differences in pain threshold and spinal reflexes
Racine et al. (2012) concluded similarly
Mogli (2012)
It is possible that women simply seek out health care services at higher rates than do men and/or
are more willing to report pain on surveys
Second, it is possible that women have higher susceptibilities to common chronic pain syndromes than men and thus will be more likely to develop conditions that feature pain as a symptom.
Last, it is possible that women have a greater sensitivity to and/or a lower tolerance of pain than men, leading to higher percentages of women crossing the threshold at which experienced pain rises to the level of a diagnosed
‘pain syndrome’
Mogli (2012)
Sex differences seem to be easier to be seen in certain pain modalities than in others (such as in heat or pressure-induced pain), using certain dependent measures (such as tolerance) and at certain time points (such as early rather than late after noxious stimulus), and exhibit small-to-moderate effect sizes
Racine suggests that the informal consensus that women are more sensitive to pain is due to a bias related to participant selection criteria and pain measures that show sex differences rather than ones that do not
This critique is too conservative in its definition of what constitutes a sex difference; the evidence is actually overwhelmingly in support of the contention that women are more sensitive to pain, although the size and importance of this sex difference could be debated. The number of studies showing increased pain threshold and
pain tolerance in males compared to females is
much larger than for a reverse direction.
Gonadal hormones
Surge of estrogen in females is associated with increased pain threshold
No convincing data on differences in pain sensitivity in females taking or not taking oral contraceptive
(Racine et al., 2012/2; Greenspan and Taub, 2013)
Hormonal replacement therapy in post-menopausal period: smaller experimental pain in females receiving gonadal hormones than those not receiving hormonal substitutes (Racine et al., 2012)
Meta-analysis of 19 pain studies (Riley et al.,1999):
A meta-analysis of experimental studies revealed that women have a higher pain threshold and tolerance during the follicular phase (with small-to-moderate effect
sizes) in every stimulus modality except electrical pain, in which the highest pain thresholds were associated with the luteal phase
Markl et al (2013)
A more recent narrative review that used a different definition of menstrual phases compared with that used in the meta-analysis concluded that increased reactivity to pain occurs peri-menstrually and mid-cycle
Generally, if effects are seen, gonadectomy increases pain sensitivity, especially for acute pain (Kuba, 2005)
By contrast, oestradiol and progesterone given to ovariectomized animals generally cause hypoalgesia (Craft, 2007).
Human studies of clinical pain are even more complex, with a multitude of findings in both directions as well as null results.
MC effects on conditioned pain modulation (Rezaii et al., J. Pain, 2012) suggest greater pain inhibition during ovulation period - No effects of MC on cold
pressor test
Brain activation changes in males and females
Derbyshire 2002
Applied painful laser stimuli to the dorsum of the hand in males and females. Females had greater activation in the peri-genual cingulate cortex, whereas males showed more distributed activations.
Naliboff, 2003
Analysed brain responses to mild rectal distension in
female and male patients with IBS.
Females had greater activations in the cingulate cortex and amygdala – regions associated with affect.
Males had greater activations than females in insula and brain stem, and prefrontal cortex (attentional and sensory
aspects of stimulation).
Thus, different brain patterns associate with visceral pain in males and females.
Greenspan&Taub (2013)
Summarised results of 11 brain imaging studies in experimental pain
Variable patterns of activations across studies, with perphaps only insula consistently yielding greater activation during painful stimulation in males than females
A methodological problem: stimulus intensity was matched to be subjectively identical in males and females only in part of studies
Gupta et al. (2017) confirmed with large number of studies the greater activation of insula in males and in the anterior cingulate cortex in females in chronic pain syndromes
Chronic pain:
Prevalence
Highly prevalent chronic pain syndromes that are found in both sexes occur overwhelmingly more often (in more than 80% of cases in which treatment is sought) in women.
Chronic pain syndromes with the highest prevalence overall — headache, migraine, low back pain, neck pain and knee pain (mostly osteoarthritis) — all have marked female predominance (LeResche, 2000; Mogil 2012)
Tighe et al. (2014)
Analysed sex differences in post-operative by collecting numerical rating scales (0-10) in 330,000 patients in over one year.
Serious surgeries: amputations, cardio-thoracic, orthopedic
In all pain measures, females had larger scores than males e.g., occurrence of severe pain events in day 1: 25.1% (F) vs. 22.5% (M)
Miaskowski and Levine (1999) : Review of 18 studies were summarised, and the conclusion was that especially the kappa-receptor opioids show greater response in females than in males
Campesi et al. (2012): Females require less opioids than males to reach comparable level of analgesia
Niesters et al. 2010: Meta-analysis of opioid analgesia in males and females in experimental pain, Morphine induces greater analgesia in females than males
in experimental pain
Patient-controlled analgesia shows stronger effects in females than males (less morphine consumption); the longer the analgesic intervention, the larger the differences between males and females.
Few studies exist on effects of non-opioid analgesics in men and women.
Walker and Carmody (1998)
Tested the analgesic effect of Ibuprofen (non-opioid anti-inflammatory drug) in healthy females and males.
Pain threshold and pain tolerance was tested using electrical stimulation of the earlobe. Only males showed analgesia related to ibuprofen. Plasma levels of ibuprofen were identical in both groups. The study indicates greater sensitivity of males to non-steroid analgesic drugs
Older studies on effects of non-opioid analgesics have not been consistently replicated (Mogil, 2012; Melchior et al., 2016).
Gender role and pain
Fillinghim et al. (2009),
Current human findings regarding sex differences in experimental pain indicate greater pain sensitivity among females compared with males for most pain modalities, including more recently implemented clinically relevant pain models such as temporal summation of pain and intramuscular injection of algesic substances
Wise et al. (2002),
Analysed pain thresholds and pain tolerance thresholds in males and females. They applied Gender Role Expectations of Pain questionnaire (GREP) to measure gender-specific expectations about pain (willingness to endure and communicate pain).
GREP was a significant, although not exclusive, predictor of pain tolerance and pain threshold in cold pressor test.
Thus, sex differences in pain perception also encompass psychosocial factor that add to the biological factors.
Pool et al. (2007)
Administered questionnaires to measure how males
and females identified themselves with “ideal men” or “ideal women”.
First study, participants indicated their gender identification and expected tolerance of a hypothetical painful stimulus. As anticipated, high-identifying men reported significantly greater pain tolerance than high-identifying women - High-identifying men tolerated more painful stimulation than high-identifying women.
High-identifying men tolerated more pain than low-identifying men. These results highlight the influence of social norms on behavior and suggest the need to further explore the role of norms in pain reporting behaviors.
Robinson et al. (2003)
Showing gender-related expectation modulation of pain thresholds
The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women
Women had briefer tolerance times and higher post–cold pressor ratings than men. When given gender-specific tolerance expectations, men and women did not differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain
Sex differences in cognitive modulation of pain
Subject and the experimenter’s genders
Levine and DeSimone, 1991
Analysed pain ratings related to cold pressor pain in males and females. Males reported greater pain if the experimenter was of the same sex than of opposite sex. This effect was not significant in females.
However, the interaction has not been confirmed in many subsequent studies (Racine et al., 2012)
Kallai (2004)
Investigated the effects of gender and professional status on the report and tolerance of pain
Subjects tolerated pain longer when they were tested by a professional experimenter. Subjects also tolerated pain longer when they were tested by an experimenter of the opposite sex. The observation that pain responsivity is influenced by the professional status of the experimenter might have implications for the study of pain
Attention
Keogh et al. 2000)
Females and males subjects, cold pressor test (CPT)
Compare the effects of two different attentional strategies (focused vs. avoidance)
Males were found to be more tolerant to cold pressor pain than females. Males reported less sensory pain when they attended toward the pain than when they avoided it. However, a similar effect was not found in women, suggesting that attentional focusing may only be a useful strategy for males.
Keogh et al 2002
Compared to females, males exhibited less negative pain responses when focusing on the sensory component of pain (i.e. increased threshold, tolerance and lower sensory pain). Emotional focusing was found to increase the affective pain experience of females. Together these results confirm that important differences exist between men and women in the effects pain coping instructions have on the experience of pain.
Evolutionary views on the origin
of sex differences in pain
Importance of sex differences:
ethics and pain therapy.
Two hypotheses have been put forward regarding the ultimate causes of sex differences in pain and analgesia. One suggests that male and female mammals are under divergent adaptive pressure with respect to the evolution of pain modulatory circuitry owing to the presumably more common exposure to traumatic pain in males and visceral pain in females. However, there seems to be no extant data directly supporting this possibility.
A second idea is based on the observation that the neural systems underlying reproductive behaviour and
analgesia in rats have extensive anatomical and neurochemical overlap. The theory postulates that
pain inhibitory circuitry may thus have ‘piggybacked’ on top of previously existing reproductive circuitry in the midbrain and brain stem (Bodnar, 2002). According to this view, the reason for sex differences in analgesia is simply that there are already sex differences in reproductive behaviour
