The Lord planned to save us from this assigned task by saying, “… Behold, the people is one, and they have all one language; … and now nothing will be restrained from them …,” later in response to perceived arrogance, He said, “… let us go down, and there confound their language, that they may not understand one another’s speech. So the Lord scattered them abroad from thence upon the face of all the earth” [Genesis 11:6-8¹], which is why it is necessary to write this chapter on ethnocultural and gender differences in the pain experience. Since the destruction of the Tower of Babel, clinicians have come to accept that there is a tremendous range of ethnocultural differences in sensitivities expressed in spoken language and behaviors. Also, as will be discussed, there are differences between the genders, with women continuing to struggle for parity with men while appropriately expecting recognition of their differences from men in cognition, affect, and behavior. We hope that the new knowledge and insight provided by this chapter will enable us to advance beyond stereotypes to an increased probability of being able to provide a more accurate diagnosis and prognosis for a given patient. The objective of practitioners of pain medicine is to reduce pain and restore pleasure, consistent with the views of many philosophies, including hedonism and utilitarianism. As noted recently by Greenblatt, “The highest goal of human life is the achievement of pleasure and the reduction of pain.”² Although pain is thought by many to be on a continuum with pleasure, some continue the ancient tradition of rejoicing in the pain of others, with vestiges still vicariously available in modern pornography.

Pain, particularly chronic pain (which persists for more than 6 months or beyond the expected time for recovery from trauma or surgery), is associated with a decline in quality of life and increases the likelihood of physical or mental disability and excessive health care utilization.³ A broad array of factors, from genotype to sociocultural forces, contributes to individual pain response.⁴ Although the primary objective of this chapter is to describe the role of ethnicity and gender in the pain experience of patients, the reciprocal influence of health care providers’ ethnocultural backgrounds and genders on their perception of their patients’ pain plus the related attitudes, beliefs, and behaviors that they bring to treating their patients should not be overlooked.^5,6 Such differences can have a significant impact on the quality and appropriateness of pain relief strategies and ethno-specific stereotypical clinical judgments, resulting in overmedication of more emotionally expressive patients or undermedication of less expressive or stoic patients.

A related issue is the large differences among ethnocultural groups in access to care, one example of which was shown by a first-year medical resident who presented the case of a 55-year-old black woman with diabetes. However, on reviewing the patient’s chart, it was noted that the resident had written that the patient was a 55-year-old white female patient. When the resident was asked if he needed to see an ophthalmologist, he responded that from concern for his patient that she was not likely to receive the highest level of care as a black woman, he noted that she was white.

With the increasing multicultural pool of both patients and providers, the need for providers to be culturally competent and to have an appreciation of health literacy becomes critical for successful pain management. The diversity in languages and comprehension now requires that clinicians ensure that they understand the depth and breadth of their patients’ chief complaints and conversely that the patients comprehend clinicians’ instructions and whether patients have sufficient self-efficacy to carry out their instructions. This chapter, therefore, primarily focuses on the ethnocultural and gender differences in clinically observed pain along with the results of studies of experimentally induced pain on self-reported thresholds of awareness and tolerance while noting the behaviors associated with the various quantitative parameters of intensity, duration, and so on.

SEX AND GENDER DIFFERENCES

A growing body of research on sex differences demonstrates that men and women perceive and cope with pain differently, including responses to specific classes of analgesic and other psychoactive medications. Although often used interchangeably, sex and gender are separate constructs. This distinction is consistent with the Institute of Medicine’s definition of sex as “the classification of living things as male or female according to their reproductive organs” and chromosomes, with gender consisting of a person’s masculine or feminine self-representations and role behaviors.⁷ Therefore, in further discussion, the term “gender” will be considered as a cultural variable as distinct from the biologically based classification as male or female sex.

Epidemiologically, women are more likely than men to report acute and chronic pain,^8,9 and they use pain-relieving medications significantly more often than men.^10,11 These findings are highly consistent across time and place, with women reporting more frequent, severe, and disabling pain involving multiple body sites than men. As noted in a recent review, the female-to-male ratio for many types of headache and orofacial pain is approximately two to one, with women also having more widespread musculoskeletal pain.¹² Moreover, the greater analgesic use by women is not simply a function of their greater willingness to report actual increased frequency and severity of pain because when pain frequency and severity are controlled, women are still 40% to 50% more likely than men to report using analgesics.¹³ Women are also more likely than men to use a variety of nonpharmacologic treatments for orofacial pain, low back pain, and other painful conditions.¹²

Obviously, biological, cultural, psychological, and social factors all contribute in various ways to ethnocultural differences in willingness to report and exhibit pain behavior. Experimental studies help to elucidate the mechanisms accounting for these gender and other cultural differences, for example, that women are more sensitive than men, as measured by subjective thresholds of pain awareness and subsequent tolerance of standardized noxious stimuli.^9,14 There are also more objective indices, such as electromyographically measured thresholds for muscle reflexes and pupillary dilation or galvanic skin response as manifestations of associated autonomic nervous system activity.¹⁵ Although experimental pain studies provide different information from clinical or epidemiologic reports, these quantitative measures, singly or in combination, do account for the significant amount of the variability observed in clinical pain.^16–18

Social Factors

Pain tolerance has been shown to be significantly greater in both genders when the experimenters are female rather than male.¹⁹ Gender as a cultural variable includes attitudes, beliefs, and behavioral role expectations for a given ethnocultural group. Differentiation by gender begins in early childhood, with boys and girls receiving different cues to interpret and express themselves in response to environmental adversities such as pain. Sanford and colleagues reported that the higher the femininity score, the lower the pain tolerance.²⁰ Robinson and colleagues found that both men and women consider females more sensitive and less tolerant of pain and more willing to report pain than males.²¹ Moreover, when controlling for willingness to report pain, females were still significantly less tolerant of experimental pain than males. In a recent meta-analysis, moderate to highly significant relationships were found between pain-specific gender roles (measured using the Gender Role Expectations of Pain Questionnaire,²¹ which asks respondents to indicate, for example, how sensitive to pain “the typical woman” is relative to “the typical man”) while obtaining laboratory indices of pain tolerance thresholds.²²

In fact, fear of pain predicted a lower tolerance for experimental heat and cold pain in men than women.²³ In clinical studies, symptoms may vary as a function of the age, gender, and ethnocultural background of the health care provider, highlighting the importance of the interpersonal context of verbal reports of pain.²⁴ In addition to classifying actual or potential patients as being worried and sick, worried but well, not worried but sick, and not worried and not sick, Barsky and colleagues^24,25 have subclassified anxious medical patients (who often have pain complaints) into hypochondriacs, who are more unconsciously motivated by preoccupations with illness, and malingerers, who deliberately feign illness, perhaps consciously seeking secondary gain. Although more women than men engage in these behaviors, both of these groups of patients overuse the health care system, regardless of gender. In European studies, both male and female physicians tended to prescribe more drugs for female than male patients with neck pain and ordered additional diagnostic work for the female patients.²⁶ The same group also reported that female physicians rated written reports by women as more “accurate, trustworthy, relevant and interesting” than those of male patients.²⁷ As described elsewhere, catastrophizing and anxiety related to fear of pain are greater in females.²⁸

Psychological Factors

Gender differences in relation to pain prevention and tolerance have been found in psychopathology, including personality disorders, anxiety, depression, catastrophizing, attentional processes, and maladaptive pain-coping strategies. Catastrophizing is associated with negative cognitive and affective and related psychopathological responses to pain, which include feelings of helplessness, pessimism, magnification, and rumination.²⁹ Anxiety and depression (as well as other negative emotional states) often accompany pain as the chief complaint and potentially confound evaluation and treatment because they are associated with increased pain severity, particularly among women;³⁰ “anxiety influences pain perception more in men than women … findings suggest that pain-related anxiety constructs [including state anxiety], but not trait anxiety, are associated with pain perception … these constructs are associated with pain intensity ratings in men and pain tolerance levels in women.”³¹

Conversely, positive emotions have also been shown to reduce pain perception in the laboratory.³⁰ Clinical pain, however, is often reported to be more intense or prolonged in depressed patients when focusing ordinarily on nonthreatening internal stimuli; that is, ordinary sensory input such as that associated with normal bodily function would not reach the threshold of awareness in nondepressed individuals but will reach the level of awareness in depressed patients.

Experimental Pain

Models of noxious stimulation used to evoke pain include pressure, thermal, mechanical, electrical, and cold pressor stimulation. The magnitude of the sex or gender differences may be a function of the method for inducing pain, including the type of the stimulus, anatomic location and duration of the stimulation, size of the area stimulated, number of stimulus repetitions, and so on.^9,32 Observed differences may also be related to how the pain-rating scales are anchored³³ and whether they are based on rating, ranking, or ratio, raising questions about the reliability and validity of subjective responses of men and women to noxious stimuli. Moreover, there may be gender differences in what is considered the endpoints of a painrating scale such as “most intense pain imaginable” or “most intense pain ever experienced.” Similarly, evaluating other “objective” or “involuntary” responses to noxious stimulation revealed that women exhibited significantly lower nociceptive flexion reflex thresholds than men.³⁴ Differences have also been reported in pain-related facial expressions among newborn infants, with female infants demonstrating more frequent and intense facial expressions of pain during and immediately after venipuncture.³⁵ Positive mood, pleasant meditation, and relaxation all help to reduce pain sensitivity. In laboratory studies, for example, Marchand and Arsenault found that positive mood-inducing odors reduced pain in women but not men, highlighting the possibility that, not surprisingly, emotional processes play a greater role in the experience of pain among women than men.³⁶

Thus, it is reasonable to expect that perceived ethnocultural congruity among the beliefs, attitudes, and behaviors related to the pain of the patient and provider will attenuate the pain experience. These observations undoubtedly support the clinical tenet that the relief provided by many integrative medicine procedures relies in part on this alliance with the patient made possible by the greater amount of time spent with patients. Although placebos are generally positive, there are occasional examples of their facilitating negative nocebo outcomes. Placebo effectiveness appears to be based on several factors, not the least of which are the ethnocultural-based beliefs of the patient that they will work. In fact, some placebo effects appear to be quantitatively dose related,³⁷ averaging approximately one-third the effectiveness of the active agents, particularly for pain relief.³⁸ In a surprising number of psychophysiological and even pathophysiological processes, placebos’ effectiveness may be observed. Many of these processes involve neurohormonal systems, which in turn are influenced by the ethnocultural differences in beliefs, attitudes, and behaviors. Unfortunately, evidence-based research specific to ethnocultural differences may be difficult to obtain, as noted by Williams.³⁹

Although not included as a therapeutic intervention elsewhere in this chapter, acupuncture had been historically used as an ethno-specific method of pain relief. Its original success in the Western world was attributed to the unique techniques of Asian providers most likely caused by a placebo effect. In more recent evidence-based research, however, there has been increasing support for a biological basis for the effectiveness of acupuncture.⁴⁰ In fact, there does not appear to be any significant difference in perceived relief of pain among various ethnic groups receiving acupuncture.⁴¹

There is in fact little in the literature suggesting gender or ethnic differences in the magnitude of placebo analgesia, although there are occasional reports of difference in levels of effectiveness for other than pain problems. For example, Latino patients were found to be more likely to respond to placebo in an antidepressant trial than were patients from other ethnic backgrounds,⁴² possibly related to differences in suggestibility.

Gender differences in the use of pain-coping strategies have been found in children, adolescents, and adults.^12,43 In general, whereas boys and men report using more behavioral distraction to manage pain, girls and women rely more on social support and positive self-statements.⁴⁴ Women catastrophize about pain more than men, substantiating the observation that catastrophizing may account for many of the differences between genders in reporting of clinical pain.²⁸

NEUROPHYSIOLOGIC AND NEUROPHARMACOLOGIC FACTORS

Central Nervous System Processing of Pain

In addition to quantitative sensory testing (QST), which repeatedly demonstrates sex and gender differences,⁹ neuroimaging research now provides better understanding of the underlying neurophysiologic mechanisms of pain responses. Functional magnetic resonance imaging (fMRI) studies using blood oxygen level–dependent (BOLD) and connectivity techniques identify areas responsible for pain perception in both men and women. In both sexes and genders, whereas BOLD activation occurs in the insula, anterior cingulate cortex, and dorsolateral prefrontal cortex,^45,46 connectivity is found between the periaqueductal gray (PAG) and the prefrontal cortex, insula, and uncus.^47,48

Consistent with gender-related behavior being a cultural phenomenon, the brain is organized and functions to accommodate the evolutionary-based dichotomous, hunter/gatherer tasks, with the brains of males being primarily interconnected during activation from anterior to cephalo-caudal posterior and the female brain with its larger corpus callosum having more interhemispheric connections.⁴⁹

Brain imaging research also indicates sex and gender differences in the affective brain regions associated with emotion in response to pain. Henderson and colleagues⁴⁶ found increased midcingulate cortex, cerebellar cortex, and hippocampus activation in women experiencing evoked pain from hypertonic saline injections. Similarly, whereas women had more connectivity between the PAG and midcingulate cortex,⁴⁷ men show greater PAG to amygdala connectivity.⁴⁸ The medial prefrontal cortex, an area thought to process inner-directed (or contemplative) information, is significantly more activated during electrical stimulation at high pain thresholds in females than in males.⁵⁰

In a recent biopsychological study, men with left-lateralized spinal pain reported greater psychopathology and quality of life factors concerns than women with left- or right-lateralized spinal pain, which together were greater than patients with right-lateralized pain.⁵¹ These differences are congruent with research by Symonds et al., who administered experimental pain stimuli to healthy men and women volunteers while recording fMRI changes, finding that the right hemisphere was more activated in men than women.⁵² The findings are also consistent with earlier work of Unruh and Merskey in which depressed patients had more pain on the left than the right side.^53,54

Analgesic and Anesthetic Mechanisms

Opioids are among our most potent analgesic medications, with three opioid receptors—μ, κ, and δ—being significantly implicated in modulating pain in humans and animals. Clinically, the μ opioid receptor is often considered the most relevant receptor because morphine and most other opioid agonists act preferentially at that site. Human experiments consistently show that μ opioid agonists have increased potency in females relative to males.⁵⁵ Interestingly, the pharmacokinetics of opioids do not necessarily explain these sex differences in analgesic efficacy, with most studies reporting no sex differences in plasma levels of morphine.⁵⁶ In general, females appear to have greater concentrations of opioid receptors, which may partially account for μ opioid agonists being found in some human studies to provide greater analgesia for women.¹¹ The analgesic effects of opioids appear to operate at the genotype level, with sex differences in the distribution of some of the polymorphisms that impact opioid responses. For example, women who have red hair and fair skin, caused by variants of the human melanocortin-1 receptor (Mc1r) gene, demonstrated significantly greater analgesic effect from pentazocine, a κ opioid, than did men or women without these variants. In addition, redheads with a nonfunctional Mc1r variant showed greater analgesic response to morphine-6-glucuronide and reduced sensitivity to noxious stimuli.⁵⁷ However, there are other reports that larger amounts of some anesthetics are required by redheads.⁵⁸

Neuroendocrine Factors

The finding that differences between boys and girls in the experience of pain are minimal before puberty but increase thereafter has led to more detailed examination of hormonal contributions to sex-related variability in pain.¹² Some studies have reported menstrual cycle–related changes in the pain responses in women based on a meta-analysis more than a decade ago that sensitivity to noxious stimuli varied in part as a function of cycle phase, with greater pain sensitivity generally noted in the late luteal phase.⁵⁹ In addition, Kuba and Quinones-Jenab found that women reported higher rates of back and head pain at the end of the luteal phase of the menstrual cycle.⁶⁰ Several reports have also directly evaluated the effects of hormone administration in women, finding that exogenous estrogen is associated with a significant increase in reports of orofacial pain (e.g., temporomandibular joint disorder) in cycling women receiving oral contraceptives.¹² Although men most likely have as yet unknown cycles, few studies have focused on the relationship between men and pain and gonadal hormones. However, one report of low-dose testosterone administration among men with angina showed an analgesic effect of testosterone.⁶¹

Related information has become available from the outcome of transgender procedures in which individuals undergoing male-to-female surgery and supportive endocrine manipulation reported increased pain after the procedures, but female-to-male transitions resulted in decreases in pain. In a 2007 study of female-to-male transsexual patients who had chronic pain, more than half showed reduced headache pain with testosterone treatment.⁶² In the same study, about one-third of the transsexual male-to-female patients who were given hormone treatment (e.g., estrogen) developed chronic pain.

Because the literature on sex and gender differences in pain and analgesic responses is inconsistent, there is always the potential for idiosyncratic treatments for a variety of pain conditions. Despite the fact that opioids increased the likelihood of hypogonadal states in men and women,⁶³ they continue to be used for patients with chronic pain. Alternatively, for patients whose symptoms vary as a function of hormonal fluctuations, such as during the menstrual cycle, it may be possible to modify treatments accordingly. Also emerging with some renewed emphasis is the relationship between pain and inflammation, which differs by sex and possibly gender.⁶⁴ Thus, health care providers need to be aware of the social context of and gender differences in the pain experience from onset through therapeutic intervention, with recognition of the differences between men and women, including awareness of the subtle cues that may influence patients’ perceptions, expectations, and behaviors associated with disparities in pain relief.⁶⁵

RACE, ETHNICITY, AND CULTURE DIFFERENCES

As noted in the introduction, both patients and providers bring their ethnocultural backgrounds, behaviors, experiences, attitudes, and beliefs to the examining room. With the increasing multicultural pool of providers, the need, as noted throughout this chapter, for cultural sensitivity and competence has become more critical for pain management clinicians. Although the terms “race,” “ethnicity,” and “culture” are frequently used interchangeably, they are conceptually quite different. Whereas “race” distinguishes groups of people according to physical characteristics, biology, or ancestry, “ethnicity” focuses on the distinction among groups of people who share a certain social background, culture and traditions, behaviors, and so on. Although skin color may be a useful distinction, largely for the cosmetic and fashion industry, race is rarely used in scientific research as a biological marker, especially with evidence of more genetic variability within than between racial groups. “Culture” typically refers to behavioral and attitudinal norms, acquired knowledge, beliefs, values, and ideas transmitted and reinforced by members of the group.^66,67 Culture thus shapes many aspects of the experience of pain, including pain expression, expectations, perceptions of the health care system, and resulting health care–seeking behavior.