Sex & Gender in Acute Care Medicine

Sex & Gender in Acute Care Medicine Chapter 9: Pain

Chapter 9: Pain James R. Miner, MD Chief, Department of Emergency Medicine Hennepin County Medical Center Professor of Emergency Medicine University of Minnesota

Opening Case • A 43 year old female presents to the ED complaining of 9/10 leg pain after a fall • She reports pain around, just below the knee • She is visibly uncomfortable and in moderate distress • Patient is given IV morphine at 1 mg/kg (7 mg total)

On exam, there is swelling and ecchymosis to the left knee and lower leg • Tenderness to palpation and pain with any range of motion • Initial dose of morphine is well-tolerated • After 15 min, patient still reports 8/10 pain

Patient is given 3.5 mg of IV morphine 15 minutes after first dose • After second dose, patient reports some pain relief (4/10) • She has now developed nausea • X-ray shows a tibial plateau fracture

Patient’s O2 saturation briefly drops to 88% • Patient noted to be somnolent but arousable • She is fitted with a Robert-Jones splint • The decision is made not to medicate patient due to hypoventilation and decreased mental status • Patient experiences severe pain during splint placement

Patient’s vital signs return to normal • Over time, patient is given 3 more doses of morphine (3.5 mg each) • She develops vomiting, continues to report pain • Decision is made not to give further pain meds • Pt is admitted to Orthopedics with continuing 6/10 pain

Introduction • Despite a wide variety of treatments, pain management is challenging and often inadequate • Early and accurate assessment are the most important aspects of effective management • Inaccurate assessment of pain is a frequent underlying cause of inadequate treatment

Introduction • Oligoanalgesia: Inadequate treatment of pain • Patient satisfaction with ED treatment often depends on: • Accurate assessment of pain • Effective treatment of pain • Discharge planning for pain relief

Introduction: Sex, Gender, and Pain • Various studies have shown increased risk for severe pain in females, including: • Decreased pain sensitivity • Increased pain facilitation • Decreased pain inhibition compared to men • ED studies have found that women are less likely than men to receive pain medication

Introduction: Sex, Gender, and Pain • Several different mechanisms have been hypothesized to explain differences in pain perception, including: • Endogenous opioid function • Genetic factors • Pain coping • Catastrophizing • Gender roles • Sex hormones

Introduction: Sex, Gender, and Pain • There may be no difference in how men and women experience pain • Difference could lie in pain expression - due to differences in communication, gendered social expectations • Alternatively, there may be a physiological difference in the degree of perceived pain between sexes

Introduction: Sex, Gender, and Pain • Differences in pain management are likely caused by a confluence of factors, including: • How pain is perceived and expressed • How pain is assessed by providers • Differing responses to pain treatments • It is presently unknown to what extent each of these factors is involved

Introduction: Sex, Gender, and Pain • Based on current knowledge, pain assessment and intervention should take into account sex- and gender-related differences • Tailored approaches to pain management may decrease the progression of untreated pain

Pain Perception • Women exhibit greater sensitivity to noxious stimuli • Compared to men, women report: • More severe pain • More frequent pain • Longer duration of pain • Evidence shows differences in pain thresholds and tolerance

Pain Perception Biological Psychosocial Cognitive or emotional appraisal of pain Pain behaviors Social roles These differences stem from biological and psychosocial differences related to sex and gender. • Nociceptive pathways • Physiology • Perceptual sensitivity

Pain Perception • Male and female subjects had their hands placed in cold water • Subject alone in room with investigator: no difference in pain between men and women • A same-sex friend in room with subject: women reported higher degrees of pain • No change in reported pain in men – even with friend in room

Pain Detection, Transmission and Expression Pain Transmission System Pain Detection System Pain Expression Pain Stimuli Second and third order neurons Nociceptors Tissue Injury Sensory and limbic cortex Perceived Suffering Modulation Experience Cultural expectations Expectation of treatment Anxiety, Stress, Fear

Pain Perception • Processing of a pain signal can be divided into 2 basic areas: • Nociceptive – the detection of pain stimuli • Neurogenic – modulation of transmitted pain signals, development of cortical response • Sex- and gender-based differences may play a role at many points in these pathways

Pain Perception • Subjective experience of pain (pain expression) is influenced by many factors • Cultural expectations, personality, past experiences, and underlying emotional state • All of these factors can be shaped by gender

The Endorphin System • Following response to pain or stress, the function of the endorphin system is to decrease this response • Endogenous opioid system responses differ between the sexes • Differences in the endorphin system could account for different responses to pain over time and to pain therapy

Clinical Evaluation • Pain is a complex, subjective interaction between perception and cognitive/emotional states • Experience of pain is not directly determined by extent of injury • Patients with identical injuries often report different amounts of pain • Pain treatment must be based on the subjective assessment of a patient’s pain

Pain Measurement • Pain is typically measured using numeric rating scales • Pain scales serve as communication tools between patient and provider • Pain score may be influenced by how a patient would like a provider to respond (i.e. a patient may report 10/10 pain to communicate that they desire some intervention)

Pain Measurement • Differences in pain scores for identical stimuli have been reported – with women reporting higher pain scores than men • Women’s pain scores are more likely to vary relative to verbally described pain • Accuracy of pain scores are likely to be improved by using a standardized assessment in conjunction with patient’s history

Acute vs. Chronic Pain • Chronic pain is pain that persists after the initial tissue injury has healed • Can be caused by injuries not expected to heal (e.g. degenerative joint disease) • Pain transmission system dysfunction (neurogenic pain) • Chronic pain conditions are reported more frequently by women than men

Treatment • Clinical studies of μ-opioid agonists have had mixed results • About equal numbers indicate superior female response, male response, and equal response • Increased evidence that women experience more adverse responses to IV opioids, particularly nausea, vomiting, and affective disoders

Treatment • 2% of US adults use some opioid monthly • Women • Are more likely to be regular and long-term users • Are prescribed higher doses relative to weight • Progress more rapidly from use to dependence • Underutilize rehabilitation services • Men • Have a higher risk of fatal overdose

Secondary Pain Factors • Acute psychological responses to pain (anxiety, depression) may vary by gender • Anxiety has a greater association with pain in women • Psychological responses can affect severity of pain and progression to chronic pain • Decreasing psychological responses to pain will likely result in better pain relief over time

Follow-Up and Prognosis • Adequate treatment of acute pain is a key step in preventing chronic pain • Acute pain can serve an adaptive purpose (ex: avoidance of repeat injury) • Chronic pain can lead to maladaptive behaviors (ex: inactivity, mood changes) • These issues should be addressed alongside issues related to the severity of the pain itself

Discussion • The effects of sex and gender on pain are complex and still largely undefined • Determining the place of sex and gender in pain treatment is challenging due to subjective nature of pain assessment • A patient-derived pain score is unlikely to be universally equivalent between men and women

Discussion • When using a pain measurement tool, pay more attention to changes in measurement rather than degree of measurement • A woman who reports her pain as an “8” is not necessarily experiencing more severe pain than a man who reports a “6” • If after treatment, the woman reports a “4” and the man reports a “3,” they have likely had similar responses to treatment

Conclusion • Men and women exhibit differences in measured pain and response to treatment • The relative importance of differences in pain detection, expression, and measurement is unknown • By being aware that differences exist, we can implement more precise and accurate assessments and more effective therapy

Case Conclusion • Simply initiating treatment does not ensure adequate pain relief • This patient had poor pain relief despite aggressive morphine dosing • A better understanding of sex and gender could have improved pain management • Knowing that anxiety is more common in women could have led to more accurate pain assessment

Case Conclusion • Understanding that the effect of opioids can be more pronounced in women could have made it clearer that a smaller initial dose may have been sufficient • A smaller initial dose could have avoided the patient’s adverse response and may have allowed for adequate pain medication during the splinting procedure • The key to pain management is accurate assessment before and after treatment

Research Questions • Further work to be done in refining pain measurement tools to account for gender differences • To allow us to compare pain and changes in pain across genders • If there are differences in pain perception, these differences should be quantified • To allow for development of pain trials that measure pain effects and treatments by sex

Pain Questions 1. Which of the following is true regarding sex and gender differences in pain? (A) Women are more sensitive to noxious stimuli than men (B) Chronic pain is more prevalent in women than men (C) Opioids are more effective at treating pain in women than men (D) All of the above Answer: (D) All of the above While much remains to be discovered about pain from a sex and gender perspective, some clear differences between men and women have emerged in this area. Studies have shown that women experience greater sensitivity to noxious stimuli, having lower pain thresholds and tolerance as compared to men. Furthermore, women report chronic pain conditions more frequently than men. On the other hand, while the evidence is mixed, some studies have shown that morphine has more of an analgesic effect and more effectively relieves pain in women as compared to men. References: 1. Miner J. Are women more sensitive? Sex and gender differences in pain perception, clinical evaluation, and treatment. In: McGregor AJ, Choo EK, Becker BM, eds. Sex and Gender in Acute Care Medicine. New York: Cambridge University Press; 2016: 122-135.

Pain Questions 2. Sex and gender affect pain through all of the following mechanisms except? (A) Pain stimulus (B) Pain detection (C) Pain transmission (D) Pain expression Answer: (A) Many factors influence the detection, transmission, and expression of pain, and nearly all of these are affected by sex and gender, both via biological and psychosocial mechanisms. For example, in a study by Olsen et al, sex and genotype interacted to affect nociceptive sensitivity, with increased sensitivity for women but decreased sensitivity for men. Sex hormones appear to modulate pain: both testosterone and estrogen increase stress-induced analgesia. In one study, women reported higher pain severity of a noxious stimulus in the presence of a friend, but not in their absence, as compared to men, highlighting the importance of relationships and communication styles in the expression of pain. Pain stimulus refers to the cause of pain (e.g., placing the hand in cold water) and is not affected by sex or gender. References: 1. Miner J. Are women more sensitive? Sex and gender differences in pain perception, clinical evaluation, and treatment. In: McGregor AJ, Choo EK, Becker BM, eds. Sex and Gender in Acute Care Medicine. New York: Cambridge University Press; 2016: 122-135. 2. Olsen MB, Jacobsen LM, Schistad EI, Pedersen LM, Rygh LJ, Roe C, Gjerstad J. Pain intensity the first year after lumber disc herniation is associated with the A118G polymorphism in the opioid receptor mu 1 gene: evidence of a sex and genotype interaction. J Neurosci. 2012;32:9831-4.

Pain Questions 3. Which of the following are risk factors for oligoanalgesia? (A) Gender (B) Age (C) Race (D) All of the above Answer: (D) All of the above Oligoanalgesia—or the inadequate treatment of pain—is a common problem in emergency departments. Among other factors, gender, age, and race have all been identified as risk factors for oligoanalgesia. One study showed that women were more likely to receive analgesia (as well as higher doses and more potent analgesics) for headache, neck pain, or back pain than men; however, a more recent study showed that men were more likely to receive opioid analgesia for abdominal pain than women. Similarly, studies have shown that both older and younger patients are at risk for oligoanalgesia. Finally, multiple studies have shown that black and Latino patients were less likely to receive analgesia for long bone fractures compared to white patients, although some studies have show no difference in rates of analgesia administration between these populations. *see next slide for references

Pain Questions Question 3 References: 1. BanzVM, Christen B, Paul K, Martinolli L, Candinas D, Zimmerman H, Exadaktylos AK. Gender, age and ethnic aspects of analgesia in acute abdominal pain: is analgesia even across the groups? Intern Med J. 2012;42:281-8. 2. Chen EH, Shofer FS, Dean AJ, Hollander JE, Baxt WG, Robey JL, Sease KL, Mills AM. Gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. AcadEmerg Med. 2008;15:414-8. 3. Jones JS, Johnson K, McNinch M. Age as a risk factor for inadequate emergency department analgesia. Am J Emerg Med. 1996;14:157-60. 4. Miner J. Are women more sensitive? Sex and gender differences in pain perception, clinical evaluation, and treatment. In: McGregor AJ, Choo EK, Becker BM, eds. Sex and Gender in Acute Care Medicine. New York: Cambridge University Press; 2016: 122-135. 5. Rupp T, Delaney KA. Inadequate analgesia in emergency medicine. Ann Emerg Med. 2004;43:494-503.

Sex & Gender in Acute Care Medicine