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4 Articles in this Series
Introduction
Individualizing Pain Treatment: Start with Gender?
Simplifying Pain Self-Management for Patients
The Interactions of Emotions and Chronic Pain
To Treat Pain Better, Underlying Mechanisms Are Key

Individualizing Pain Treatment: Start with Gender?

with Inna Belfer, MD, PhD, and Rollin Gallagher, MD

When evaluating a new patient with pain, doctors may first think about the location of the pain, the potential mechanism, the severity or the age of the patient.

Inna Belfer, MD, PhD, has another idea: First, consider gender. “The approach to the patient should be individualized, first of all, based on sex, then age,” said Dr. Belfer, health scientist administrator at the National Institutes of Health (NIH) Office of the Director. She spoke at the American Pain Society (APS) 2018 Scientific Summit on ‘‘Sex Differences in Pain and Analgesia”1 in Anaheim, California, where understanding varying mechanisms in pain were the focus.

“We should not treat men and women equally as an average patient,” she said, referring to the myriad of gender differences that need to be taken into account. She also discussed the National Institutes of Health initiative, “Sex as a Biological Variable,”2 which took effect in January 2016. The policy incorporates a review of gender considerations in research grant applications and encourages taking gender into account in both research and clinical care.

How Different is Pain in Men and Women?

Very different, Dr. Belfer told the APS audience. Among the differences, she explained, are that men and women have unique experiences in:

  • responses to experimental pain
  • pain symptoms
  • attitudes, including reporting pain and symptoms
  • prevalence rates of acute and chronic pain
  • responses to analgesia
  • genetic influences on pain.

The sex prevalence of various painful disorders is well known, she stated. For instance, female prevalence is seen in migraine headache with aura, Tic douloureux, carpal tunnel syndrome, Raynaud’s disease, and esophagitis, to name a few. Male prevalence is found in pancreatic diseases, duodenal ulcer, abdominal migraine, and ankylosing spondylitis, among others.1

In addition, there are differences in post-surgical pain experiences among men and women, said Dr. Belfer. Citing research in more than 10,000 patients, she shared that men report more pain after major operations, while women report more after minor procedures.3 In general, she says, ‘‘women have a lower pain threshold and a higher willingness to acknowledge pain.”

Until the past decade or so, most scientific research—not just for pain research, but all areas of research—included mainly middle-aged white males, Dr. Belfer noted. Studying gender differences is crucial not only to fight stereotypical views, such as “the pain is all in your head,” but also to understand brain-related disorders with sex differences in their incidence or nature, and to explain contradictory findings, she said.

Considering Known Differences in Practice

While research on gender differences in pain and pain treatment is not yet common, researchers have looked at some differences that may be helpful in assessing patients. For instance, the following distinctions have been noted in opioid analgesia, according to Dr. Belfer:

  • In a meta-analysis of 25 studies, researchers found greater opioid consumption in men than in women.4
  • Morphine had a slower onset of action in women but was more potent.5
  • K-opioids (pentazocine) may provide more pain relief in women.6
  • Women carrying the HPS haplotype may be the most sensitive to capsaicin-induced pain.7

As research accumulates, sex-specific assessment taking genetics and other factors into account may be possible, she said.

SABV Policy May Help

Pain research studies, as well as research in other areas, will have increased focus on gender differences, due to the NIH program. The NIH expects that ‘‘sex as a biological variable will be factored into research designs, analyses, and reporting invertebrate animal and human studies.”2 Reviewers and researchers are expected to follow what Dr. Belfer calls the “four Cs:”

  • Consider that the design of studies take sex into account or explain why it is not.
  • Collect and tabulate sex-based data.
  • Characterize the data.
  • Communicate it by publishing it.

Perspective

In terms of pain sensitivity, ‘‘sex differences reveal themselves early in life,” said Rollin Gallagher, MD, MPH, clinical professor of psychiatry and anesthesia at the University of Pennsylvania, Philadelphia, who attended the APS session. “Epidemiological studies show great differences in several [pain] conditions indicating that gender may be responsible for vulnerabilities to pain conditions and require different approaches.”

As for Dr. Belfer’s suggestion to consider a patient’s gender, followed by age, Dr. Gallagher noted, “Both are important,” along with several other factors such as details about the pain condition itself.

Sources

1. Belfer I. Sex Differences in Pain and Analgesia. Presented at American Pain Society Scientific Summit. March 4-6, 2018, in Anaheim, California.

2. NIH. Consideration of Sex as a Biological Variable in NIH-funded Research. Announced June 9, 2015. Available at: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-102.html. Accessed March 26, 2018.

3. Presented at the European Society of Anaesthesiology. May 31-June 3, 2014, in Stockholm, Sweden.

4. Niesters M, et al. Do sex differences exist in opioid analgesia? Pain. 2010;151L(1):61-68.

5. Sarton, et. al. Sex differences in morphine analgesia: an experimental study in healthy volunteers. Anesthesiol. 2000;93(5):1245-1254.

6. Gear RW, et. al. Kappa-opioids produce significantly greater analgesia in women than in men. Nat Med. 1996;2(11):1248-1250.

7. Belfer I, et al. Pain modality- and sex-specific effects of COMT genetic functional variants. Pain. 2013;154(8): 1368–1376.

Next summary: Simplifying Pain Self-Management for Patients
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