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Gender Differences in Pain and Its Relief


SUMMARY

The topic of sex and gender differences in pain and analgesia has garnered progressively more interest from the pain research community over the last 15 years. The field has moved from asking whether there are meaningful sex or gender differences in pain to asking what conditions and mechanisms contribute to such differences. These questions have been explored in terms of both clinical and basic science research. Although there is overwhelming evidence that women are more burdened with clinical pain and are more sensitive to experimental pain than men are, this broad generalization is replete with exceptions. Explorations into the basis for such differences have involved social, psychological, physiological, and genetic studies, with each of these domains contributing factors to the expression of sex or gender differences in nociception, pain, and analgesia.

Introduction

“Sex matters. Sex, that is, being male or female, is an important basic human variable that should be considered when designing and analyzing studies in all areas and at all levels of biomedical and health-related research … [Furthermore,] the study of sex differences is evolving into a mature science. There is now sufficient knowledge … to allow the generation of hypotheses. The next step is to move from the descriptive to the experimental …” ( ). So concluded a committee of the Institute of Medicine of the U.S. National Academy of Sciences in 2000 that had been charged to report on the topic understanding the biology of sex and gender differences. The import of this pronouncement is as compelling now as it was more than a decade ago.

Prior to the mid-1990s, there was only occasional and sporadic interest in the question of whether there are important sex differences related to pain. Several epidemiological studies indicated that some pain conditions were more prevalent in one sex than in the other. In addition, a few studies of experimental pain sensitivity reported greater pain sensitivity in women than in men. However, this topic was not a major one for pain research. This situation began to change after the appearance of several seminal reviews on the topic of sex and gender differences in pain ( , , , ).

Since then, this topic has grown into a field of its own, as indicated by the tremendous growth in publications and activity in this area. This includes a consensus report ( ), and two special issue journals devoted to the topic of sex, gender, and pain ( , ). Here, we review what sex and gender differences have been reported in the scientific literature and the mechanisms that are thought to underlie them, as derived from both human and animal studies.

What are the Sex and Gender Differences in Pain?

Epidemiology and Sex Prevalence of Painful Diseases

Clinical and epidemiological studies have shown that many more painful diseases demonstrate a higher female prevalence than a male prevalence ( Box 15-1 ), particularly for pain conditions involving the head and neck, of musculoskeletal or visceral origin, and of autoimmune cause. Furthermore, considering pain of unspecified or uncertain origin, epidemiological studies consistently reveal that women report more severe levels of pain, more frequent pain, pain in more areas of the body, and pain of longer duration than that reported by men ( , , , ).

Box 15-1
Painful Disorders with Documented Sex Differences in Prevalence and Reported Sex Ratios When Available
From Holdcroft A, Berkley KJ: Sex and gender differences in pain and its relief. In McMahon SB, Koltzenburg M, editors: Wall and Melzack’s textbook of pain, 5th ed, Amsterdam, 2005, Elsevier, pp 1181–1198.

Craniofacial Pain

Female Prevalence (Female:Male)

  • Headache (general or specific): cervicogenic headache (history of neck injury), chronic tension headache, migraine with aura, post–dural puncture headache

  • Atypical odontalgia (2:1)

  • Burning mouth (tongue)

  • Carotidynia

  • Chronic paroxysmal hemicrania

  • Occipital neuralgia

  • Odontalgia (without pathology)

  • Temporal arteritis

  • Temporomandibular disorder (2–9:1)

  • Trigeminal neuralgia (tic douloureux) (2:1)

Male Prevalence (Male:Female)

  • Headache (specific): cluster headache, migraine without aura, post-traumatic

  • Paratrigeminal syndrome (Raeder’s syndrome) (>10:1)

  • Trigeminal post-herpetic neuralgia

Limbs

Female Prevalence (Female:Male)

  • Carpal tunnel syndrome (5:1)

  • Chilblain

  • Chronic venous insufficiency

  • Peroneal muscular atrophy (Charcot–Marie–Tooth disease, sex-linked inheritance)

  • Piriformis syndrome

  • Raynaud’s disease (5:1)

  • Reflex sympathetic dystrophy

  • Scleroderma (3:1)

Male Prevalence (Male:Female)

  • Brachial plexus neuropathy

  • Gout

  • Hemophilic arthropathy (sex-linked inheritance)

  • Intermittent claudication (lifestyle)

  • Meralgia paresthetica (lateral cutaneous nerve neuropathy)

  • Thromboangiitis obliterans (Buerger’s disease) (>9:1)

Internal Organs

Female Prevalence (Female:Male)

  • Chronic constipation

  • Esophagitis

  • Gallbladder disease (lifestyle)

  • Interstitial cystitis

  • Irritable bowel syndrome (2–5:1)

  • Proctalgia fugax

Male Prevalence (Male:Female)

  • Duodenal ulcer (<2:1)

  • Pancoast’s tumour (bronchogenic carcinoma, potential contributory causes, lifestyle)

  • Pancreatic disease

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