Added: Jermon Jess - Date: 10.12.2021 03:53 - Views: 13787 - Clicks: 5794
Try out PMC Labs and tell us what you think. Learn More. The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. The pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences.
Attention is now directed toward understanding 1 what conditions lead to the expression of sex and gender differences in pain experience and reactivity, 2 what mechanisms underlie these differences, and 3 how these differences can inform clinical management of pain. Given the substantially greater prevalence of many clinical pain conditions in women vs. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer — a woman — is a female animal.
If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people.
Two issues of terminology are important. Gender is often conceptualized as a dichotomous variable, yet individuals differ in the degree to which they conform to the norms for masculinity and femininity in their particular culture.
Thus, gender is most accurately regarded as a continuous variable ranging from exclusively feminine to exclusively masculinewith most individuals Ladies seeking sex Loop Loop Washington somewhere along the continuum of maleness to femaleness on a range of characteristics. Even within the same society, gender role expectations may differ for generations born at different times, and within an age-cohort, gender role expectations may change as a function of age. Finally, in any statistical analysis of human subjects, the dichotomous variable sex male vs.
That is, in human studies in which the dependent measure is pain report, group differences are likely to be attributable to both sex and gender. Therefore, both constructs should be examined when possible in order to understand their relative contribution to differences in pain between men and women.
In addition, methodological issues that are specific to pain research are discussed below. It is generally agreed that the first stage of any sex difference study should be a comparison of gonadally intact adult females and males. However, a failure to observe sex differences in pain can be interpreted in multiple ways: 1 no sex difference exists; 2 the observed sex difference occurs only when females are in a particular stage of the menstrual or estrous cycle e.
Thus, in the case of a negative finding when comparing gonadally intact females vs. For example, adult male rodents have greater percentage of body fat than females [ ], while the opposite is true for humans [ 78 ]. This sexual dimorphism can affect the distribution of highly lipophilic drugs, and therefore influence analgesic drug potency, efficacy, and duration of action.
Other aspects of pharmacokinetics, including liver metabolism and membrane transport, may differ between the sexes , possibly affecting analgesic potency, efficacy, and duration of action. Immune responses also differ between the sexes [ 21 ], which may contribute to sex differences in response to chronic inflammatory and neuropathic pain. The activity level of female rodents varies Ladies seeking sex Loop Loop Washington across the estrous cycle [ 2474 ], which may introduce a confound on pain tests that allow subjects to locomote freely, such as the hot-plate test.
Lastly, adverse effects of analgesics such as respiratory depression and nausea may occur differentially in females vs. As described by Becker et al. Organizational effects can only be practically examined in animal studies. Several recent reviews have described the multiple ways in which estrogens, progestins, and androgens may modulate nervous system function related to pain and analgesia [ 564143, ].
The value of testing female rodents at different stages of the estrous cycle is debatable. In rodents, an influence of estrous cycle stage is not necessarily indicated by larger observed variance [ ]; therefore, large samples are typically required to adequately power studies examining females in specific stages of the estrous cycle. One of the most reliable and simple ways to determine stage of the estrous cycle in rodents, sampling vaginal cytology, requires that females be handled and probed daily for at least two cycles approximately 8—10 days. Given that females and males often respond differently to acute stressors e.
Obtaining repeated vaginal samples in rodents also may affect sensitivity to drugs [ ]. An alternative to daily vaginal lavage is to measure motor activity in the home cagewhich peaks during proestrus [ 24 ].
Because rodent estrous cycles differ substantially from primate menstrual cycles Fig. If females in different stages of the estrous cycle are tested, it is imperative that the investigator explicitly state how the stages — particularly the stage of most dramatic hormone change, proestrus — are defined, as there is more than one way to deate stage of cycle. Patterns of estradiol, progesterone, and leuteinizing hormone LH in humans a and rats b during the reproductive cycle. Time unit of the x -axis in a is days; in bit is hours. After the LH surge, progesterone is elevated in both rats and women.
Reproduced from [ 17 ], with permission. In humans, while it may not always be important to test at different stages of the menstrual cycle, it is always important to consider whether such testing is appropriate. If menstrual cycle itself is not a factor to be evaluated, the investigator should plan to evaluate women in the same phase of their cycle.
There is no one ideal phase of the cycle to choose. Both absolute and relative hormonal levels could influence pain. Times of rapid change in hormone levels e. Start date of the last menstrual period can be reliably obtained from self-report, as can year and month of menarche [ 77 ]. A of methods, including analysis of daily vaginal secretions, basal body temperature, and ovulation kits can provide information on the occurrence and approximate timing of ovulation, although some methods are more reliable than others [ 17 ] p. Prediction of ovulation using urine-based home ovulation testing kits to assess leuteinizing hormone surge is a minimum standard in studies in which the menstrual cycle is of interest.
These kits are relatively inexpensive, are Ladies seeking sex Loop Loop Washington for subjects to use, and have high sensitivity and specificity for detecting ovulation [ ]. Additional measurement of blood or salivary levels of mid-luteal progesterone can confirm ovulation [ ]. Although serum-based measurements are still the most widely used and considered the gold-standard for clinical research, saliva-based methods can be an alternative.
Saliva-derived hormone measures reflect the fraction of the hormone that exerts biological effects [ ]. Furthermore, collection of saliva is non-invasive and pain-free; with appropriate instruction, the subject can collect saliva at home and store it in a home freezer without deterioration of the sample [ 66 ].
A serious drawback is that salivary hormone levels may be below detection levels. Additionally, standardization across laboratories can be a problem. It should be noted that both serum and salivary measures of estradiol and progesterone exhibit great between-subject variability within the range of normal.
However, because menstrual cycle length varies between and within women [ ], and hormone levels also vary from one day to the next in some phases of the cycle, if hormonal status is a critical variable in the research, it is best measured directly rather than inferred from self-report and ovulation measures of menstrual cycle phase.
The standard deations for stages of the menstrual cycle menstrual, follicular, ovulatory, and luteal are gynecological terms based on reproductive function. Thus, researchers must consider whether their interest is in reproductive function or in the relationship of hormone levels to pain. If the interest is in hormone levels, the gynecological nomenclature and the lack of standardization with which it is applied represents an obstacle to progress in the field . We propose that use of the terms menstrual, follicular, ovulatory, and luteal be discouraged in human clinical pain studies, unless coupled with report of the actual days of the menstrual cycle, standardized to a day cycle based on ovulation testing.
One statistical standardization method is described by LeResche et al. For these reasons, hormone levels should be reported when available. If the research question is specifically cycle -related, as opposed to hormone-related, subjects with irregular cycles should be excluded.
However, it is difficult to exclude irregularly cycling subjects based only on self-report; many subjects who describe their cycles as regular in fact have irregular cycles [ ]. Even monitoring cycles before study enrollment may not solve this problem because there are no agreed criteria for distinguishing between a regular and irregular cycle. If the research question concerns the relationship between pain and hormone levels or hormone variability and hormones are measured directly, including irregularly cycling subjects may not be a problem, provided sufficient hormonal variability occurs.
However, this approach assumes that the neurohormonal processes related to pain are comparable for women with regular and irregular cycles, which may not be the case. Finally, it is important to record dysmenorrheal status, as dysmenorrheic women may differ from those without dysmenorrhea in their responses to non-menstrual pain stimuli, especially during the perimenstrual period e.
Circadian rhythms have been documented for steroid hormone levels [ 26], autonomic nervous system activity [ 27 ], and drug absorption [ 36 ]. These rhythms may be altered by menstrual cycle rhythms in women. For example, at the time of ovulation, decreased absorption of drugs such as aspirin and alcohol occurs and intestinal transit times are longer in the late luteal phase, during pregnancy and with hormone supplementation; these effects can influence drug onset time.
With a few exceptions e. Inclusion of non-cycling subjects may be of interest at specific life stages pre-puberty, pregnancy, menopause. The conventional standard is to define puberty according to Tanner stages [ ], based on clinical examination of development of secondary sex characteristics.
Self-report measures with sufficient reliability and validity are available for use in studies where direct examination is not feasible [ 25 ]. Date of menopause is the date of the last menstrual period. Standardized criteria for stages of the menopausal transition are also available [ 83 ]. If pregnant women are studied, stage of pregnancy should be clearly noted, as pain responses are known to change dramatically over the course of pregnancy e.
Reproductive history also may be important to document. For example, pain during breastfeeding in the first week postpartum is directly predicted by parity, with women who have given birth to more children experiencing more pain [ 87 ]. Conversely, in the laboratory and not in close proximity to birthmultiparous women have higher pain thresholds than nulliparous women [ 82 ]. However, it is important to keep in mind that hormone depletion via gonadectomy alters the physiological status of the animal in two ificant ways.
First, surgery can affect pain thresholds [ 93] and sensitivity to analgesics.Ladies seeking sex Loop Loop Washington
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