Abstract
Chronic pain is common among young women, and the prevalence is increasing. This increase has been associated with an upsurge in opioid use, which has, in part, contributed to a rapid rise in the incidence of neonatal opioid withdrawal syndrome. Any painful condition that occurs in young women can coexist with pregnancy; pregnancy itself has a variable impact on chronic pain conditions. Common chronic pain conditions include headache, fibromyalgia, pelvic pain, rheumatoid arthritis, and back pain. Pain before and during pregnancy and delivery, and severe pain in the early postpartum period, are predictive of persistent pain after delivery. Management of pain during pregnancy and the peripartum period relies on integration of a biopsychosocial model of support inclusive of nonpharmaceutical and pharmaceutical management. Interventional therapies, including nerve blocks, in situ stimulators, and intrathecal pumps may be used, although fluoroscopy should be strictly avoided unless absolutely necessary. It is not known whether interventions to prevent and treat acute postdelivery pain can decrease the risk for developing persistent pain, but this is an evolving area of active research.
Keywords
Migraine, Back pain, Pelvic pain, Fibromyalgia, Arthritis, Anticonvulsants, Antidepressants
Chapter Outline
Predictors of Chronic Pain after Childbirth, 1033
Common Chronic Pain Conditions in Pregnant Women, 1037
Management of Chronic Pain during Pregnancy, 1038
Multimodal Approach, 1038
Nonpharmacologic Interventions, 1039
Pharmacologic Treatments, 1039
Interventional Treatments, 1048
Prophylaxis, 1048
Management of Intractable Pain after Delivery, 1048
Chronic pain is common among young women. According to the 2016 Health, United States Report , 25% of women of childbearing age (18 to 44 years of age) report migraine headaches, 26% report low back pain, and 15% report neck pain. An increasing prevalence of chronic pain conditions in recent years has been attributed to a rise in risk factors, including obesity, sedentary lifestyle, and social and socioeconomic circumstances. The increasing prevalence of chronic pain is associated with an exponential increase in opioid use, which has contributed, in part, to the rapid rise in the incidence of neonatal opioid withdrawal syndrome in recent years ( Fig. 42.1 ). This increase is not restricted to the United States. As far back as 2001, Blyth et al. reported a 10% to 15% prevalence of chronic pain in women of childbearing age in Australia, with doubling predicted by 2050.
Any painful condition that occurs in young women can coexist with pregnancy, and pregnancy itself has variable impact on chronic pain conditions. Common chronic pain conditions in women include headache, fibromyalgia, pelvic pain, rheumatoid arthritis, and back pain. Although migraine and autoimmune disease–mediated symptoms often improve or even resolve in pregnancy, back pain and pelvic girdle pain frequently worsen as a direct result of the pregnancy.
In a prospective study of 133 nulliparous women with uncomplicated singleton pregnancies recruited in the third trimester at a large perinatal center in Canada, 38% reported a chronic pain condition or pain before pregnancy, and 55% reported pain during the current pregnancy. Forty-three percent of the cohort reported pain that persisted at 2 weeks postpartum and 25% at 3 months postpartum. Table 42.1 summarizes the characteristics of pain reported before pregnancy; migraine was the most common source of chronic pain, and lower back pain was the most common source of pain overall. Pain during pregnancy was primarily described as mild or discomforting ( Table 42.2 ); the average numerical rating scale (NRS; 11-point scale from 0 to 10) was 4. Lower back, hips, legs, and feet were the most common sites of pain. Table 42.3 summarizes pain characteristics at 3 months postpartum ; lower back pain was the most common site of pain. Not surprisingly, prepregnancy and early postpartum pain was predictive of pain after delivery. Although pain before pregnancy is predictive of pain after delivery, pain during pregnancy and delivery can presage pain that persists during the postpartum period and beyond.
| Frequency | |
|---|---|
| Chronic pain condition and/or pain before pregnancy | 38% |
| Chronic pain condition | 28% |
| Migraine | 10% |
| Irritable bowel syndrome | 6% |
| Back pain | 1% |
| Other | 11% |
| Pain before pregnancy a | 17% |
| Lower back | 11% |
| Hips | 5% |
| Genital/pelvic | 5% |
| Legs | 5% |
| Feet | 6% |
| Head | 3% |
| Other (wrists, knees, neck, shoulders) | 7% |
a Pain before pregnancy was defined as pain more than once per week or more than five times per month.
| Pain Variable | Frequency |
|---|---|
| Incidence of pain a | 55% |
| Site of pain b | |
| Lower back | 41% |
| Hips | 28% |
| Legs | 19% |
| Feet | 22% |
| Head | 8% |
| Other (ribs, upper back) | 23% |
| Present pain intensity | |
| No pain | 9% |
| Mild | 13% |
| Discomforting | 29% |
| Distressing | 3% |
| Horrible | 0.75% |
| Excruciating | 0.75% |
| Pain severity | Median [IQR] |
| Average pain score during pregnancy c | 4 [3–6] |
| Worst pain score during pregnancy c | 6 [5–8] |
| Average unpleasantness score of pain during pregnancy c | 6 [4–7] |
a Pain during pregnancy was defined as pain more than once per week or more than five times over the past 4 weeks.
b Patients were allowed to select more than one site.
c 11 point scale (0 to 10) with 0 = no pain and 10 = worst pain.
| Pain Variable | Frequency |
|---|---|
| Incidence of pain a | 25% |
| Site of pain b | |
| Lower back | 13% |
| Hips | 5% |
| Legs | 5% |
| Feet | 3% |
| Head | 3% |
| Other (abdomen/incision site, knee, mid-back, wrist) | 11% |
| Present pain intensity | |
| No pain | 5% |
| Mild | 9% |
| Discomforting | 9% |
| Distressing | 2% |
| Horrible | 0% |
| Excruciating | 0% |
| Pain severity c | Median [IQR] |
| Average pain score during the last month | 4 [3–6] |
| Worst pain score during the past 2 weeks | 6 [4–7] |
| Average unpleasantness score of pain during the past 2 weeks | 5 [3–7] |
a Pain at 3 months postpartum was defined as pain more than once per week for the past 2 weeks.
b Patients were allowed to select more than one site.
c 11 point scale (0 to 10) with 0 = no pain and 10 = worst pain.
This chapter will identify factors that have been noted to be predictive of pain during pregnancy and persistence of pain during and after delivery. It will address the most common pain syndromes that complicate pregnancy and the pharmaceutical and nonpharmaceutical management approaches indicated for treatment of pregnant patients with chronic pain. Finally, the management of pain in women with chronic pain conditions during and after pregnancy will be discussed.
Predictors of Chronic Pain After Childbirth
A small number of patients will have new and persistent pain after cesarean and vaginal delivery. The estimated number of women with persistent pain has varied widely among studies, in part related to the study design and the population studied. Some studies with very high estimates used a retrospective cohort design that suffers from recall bias, and others with the lowest estimates discontinued prospective follow-up of enrolled patients at the first report of no pain and thus may have missed those with episodic symptoms. Although most women have an uneventful recovery from peripartum pain and use opioids only briefly in the peripartum period, a 2016 systematic review and meta-analysis that included 15 studies suggested that 11% of women who deliver by cesarean report chronic pain at 12 months postpartum or later. Among women who had chronic pain, 10% described severe pain, 24% described moderate pain, and 50% described mild pain at 6 months.
Intrinsic Patient Factors
Many studies have proposed predictors of persistent pain, opioid use, and poor recovery after childbirth. A large prospective study followed women after planned vaginal delivery until resolution of pain, opioid use, and functional recovery (composite outcome). Factors predicting the longest resolution of the composite outcome were investigated. Even after correction for the effect of cesarean delivery, induction of labor was strongly predictive of more severe pain, prolonged opioid use, and delayed functional recovery. Cesarean delivery was predictive of longer use of opioid analgesics compared with vaginal delivery. Prenatal anxiety and poor physical function were also predictive of prolonged opioid use. The pain score reported on postpartum day 1 was predictive of overall postpartum pain burden and prolonged time to functional recovery. Poor breast-feeding on postpartum day 1 was also predictive of prolonged opioid use.
Preexisting Chronic Pain and Postpartum Pain
The strongest predictor of postpartum pain is previous chronic pain. Additionally, in women without a history of chronic pain, severe pain in the early postpartum period is a predictor of persistent pain after childbirth. Possible reasons for this association include a more extreme response to the normal tissue trauma of delivery, inadequate response to normally prescribed analgesics, or a kindling response in which the experience of extreme pain makes one more sensitive to subsequent stimuli. It is unknown whether aggressive pain treatment in the early postpartum period is protective for the initiation of chronic pain.
Patient Expectations
Patient expectations greatly impact the experience of pain. In a large, multicenter study of the association of maternal expectations with labor pain, the most satisfied mothers were those who expected more pain and had good pain relief from their analgesic treatment. Another study found that women’s preoperative expectation of pain was predictive of the severity of acute post–cesarean delivery pain at rest but not during activity. Simply asking women how much pain they expect and allowing them to choose a high- or low-dose pain regimen allows for better pain control and increased patient satisfaction. These results suggest that key factors predictive of post–cesarean delivery pain severity are the parturient’s expectation of pain and autonomy in its management.
Anxiety and Depression
The interaction between pregnancy, pain, and emotional distress is complex and multidirectional. Preexisting chronic pain disorders are associated with absenteeism, depression, and disordered sleep during pregnancy. The severity of postdelivery pain and the likelihood of developing chronic pain after childbirth has been shown in numerous studies to be associated with psychological comorbidities, particularly depression and anxiety.
Anxiety is a complex state with both intrinsic and environmental contributions. The prevalence of generalized anxiety and pregnancy-related anxiety in early pregnancy is high. Maternal anxiety is associated with genetic variability in the catechol- O -methyltransferase gene (COMT) that encodes for regulation of response to catecholamines. The finding that a preoperative increase in blood pressure is strongly correlated with postpartum pain may be reflective of these genetic differences. In several studies, anxiety was predictive of increased labor pain and requirement for analgesia. Higher prenatal state anxiety scores were associated with higher mean pain scores and greater opioid consumption within the first several days after cesarean delivery. Similarly, in a large French cohort, persistent pain 6 months after cesarean delivery was also associated with preoperative anxiety.
Depression is also closely linked with chronic pain. Both prepregnancy anxiety and depression were predictive of physiosomatic symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) during pregnancy and postpartum. In a large, prospectively followed cohort, women with severe acute postpartum pain had a threefold increased risk for postpartum depression compared with women who had mild postpartum pain.
Genetic and Epigenetic Variability
In addition to COMT, the experience of postpartum pain and opioid use may also be associated with genetic variability in other genes, including the gene encoding the µ-opioid receptor (OPRM1). Data, however, are inconsistent. In one study, higher experimental pressure pain thresholds, but higher heat pain ratings, were observed in women who express the OPRM1 G118 allele. In a study in Asian women who received intrathecal morphine post–cesarean delivery analgesia, women with the G118 allele had higher pain scores and required a higher rescue dose of intravenous morphine. In another study in women of mixed ethnicity, no differences were observed in pain scores and rescue opioid requirements in women who received intrathecal morphine post–cesarean delivery analgesia. Possible explanations for these conflicting results include lack of control for other variables likely to influence pain after cesarean delivery, epigenetic influences on gene expression, the presence of linkage disequilibrium, differences in response to various pain stimuli, and differences in metabolic enzymes, transporters, and signal transduction pathway molecules, among otherexplanations.
There is also complex interplay between genetic variability in cytochrome P450 (CYP) enzymes required for opioid metabolism and pregnancy. For example, CYP2D6 is induced during pregnancy. After the administration of codeine, oxycodone, tramadol, and hydrocodone, increased expression of the metabolic enzyme, combined with intrinsic genetic variability in receptor affinity for opioid ligands, affects both production of the active opioid metabolites morphine, oxymorphone, O-desmethyltramadol, and hydromorphone, respectively, and their signal transduction.
Little is known about epigenetic effects on gene expression and their possible link to pain in pregnancy. Epigenetic processes, including DNA methylation, histone modifications, and the activity of microRNAs, have been shown to alter the sensitivity to pain in nonpregnant individuals. The most commonly described epigenetic change, methylation, normally reduces gene transcription. Methylation of the gene for transient receptor potential ankyrin-1 (TRPA1) is inversely associated with the threshold for heat-induced pain and alters pressure-induced pain. Hypermethylation of the promotor for TRPA1 is associated with a low threshold for clinical pain. Decreased DNA methylation in genes related to the stress response and free radical clearance has been found in patients with fibromyalgia. The interaction between prepregnancy pain experiences and the hormonal and physiologic changes of pregnancy, and as well as effects on epigenetic modulation, is an important area for future research.
Environmental Factors
Sleep deprivation accentuates responses to noxious stimuli. Research subjects who sleep less than 6.5 hours per day have greater sensitivity to experimental pain than rested individuals. Sleep deprivation accentuates pain, and pain in turn interrupts sleep, creating a vicious cycle that commonly exacerbates pain after delivery. Painful labor lasting many hours to days may precede delivery. Afterward, care of the newborn requires frequent interruptions in sleep. It is important to facilitate sleep as a therapeutic intervention as much as possible by decreasing environmental stimuli and reducing light during the evening to prevent exacerbation of chronic pain.
Stress is also an important factor that can worsen postsurgical pain and can facilitate conversion of acute to chronic pain. Antepartum stressors induced by fear of surgery, parenting, or other changes that are associated with childbirth may factor into postdelivery pain. In nonpregnant patients who underwent back surgery, preoperative report of worry and intrusive memories were associated with chronic preoperative pain, failed back syndrome, and chronic postoperative pain. In the same study, biochemical evidence of preoperative stress, as measured by abnormal reactivity of the hypothalamic-pituitary-adrenal axis, was also associated with prolonged chronic pain after surgery. Evidence specific to obstetric surgery is limited, but there is no reason to expect that the common stressors that accompany a significant life change such as childbirth, and specific individual stressors, would not have a similar impact on post–cesarean delivery pain and conversion to chronic pain.
In summary, the presence of intrinsic and extrinsic factors predicts severe acute pain. Additionally, conversion from acute to chronic pain is associated with the presence of these factors. Patients may have an intrinsic tendency toward severe pain in response to injury. This tendency toward severe acute pain and its persistence may be genetically inherited or may be acquired through life experiences expressed through epigenetic changes. Measurement of these predictive factors with validated scales may be useful in identifying a subset of women for whom aggressive treatment of acute postsurgical pain with multimodal analgesia may prevent conversion of acute to chronic pain
Depression, anxiety, sleep deprivation, and disability, in addition to being risk factors for the development of chronic pain, are predictable consequences of severe acute pain, thus creating a positive reinforcing cycle. Interruption of this cycle by predicting and treating severe pain after delivery may be critical to preventing the development of acute severe and chronic pain. Identification and treatment of coexisting psychological distress and sleep disorders are key to effective postoperative pain management and may prevent conversion of acute to chronic pain.
Common Chronic Pain Conditions in Pregnant Women
Migraine
Migraine and other headaches are common in women of reproductive age, with a peak prevalence of up to 25% per year in women between 30 and 40 years of age. A majority of women with migraine experience improved symptoms or even symptomatic remission during pregnancy, but migraine symptoms will worsen during pregnancy in 4% to 8% of women. Some women experience a first migraine in pregnancy, usually during the first trimester. In a cohort study of 3480 women who reported migraine during pregnancy, 73% reported using antimigraine drugs, including nonopioid analgesics (54%) and triptans (25%). Headaches are very frequent during the first 8 weeks after delivery and more than one-half of women will return to baseline frequency and severity of migraines within the first month after delivery. As such, understanding the safety and role of both abortive and preventive migraine treatments during pregnancy and breast-feeding are important.
Migraine preventive therapy can often be discontinued in pregnancy given the high likelihood of improvement in frequency of attacks and severity of symptoms during pregnancy. Behavioral sleep modification and dietary changes should be the first-line therapy for women with significant migraine burden in pregnancy, as placebo-controlled trials have demonstrated significant efficacy in female chronic migraineurs. Pharmaceutical prophylaxis is recommended in pregnancy if women continue to experience frequent and/or prolonged severe attacks, especially if there is limited response to symptomatic treatment or significant nausea, vomiting, or evidence of fetal compromise (see later discussion).
Back Pain
Preexisting chronic back pain is reported in 2% of women who become pregnant, but more than two-thirds of women complain of back pain over the course of pregnancy. Back pain persists postpartum in approximately 25% of women, and there is significant relapse in subsequent pregnancies. Proposed etiologies include weight gain, increased lumbar lordosis, and inefficient core muscle control (see Fig. 2.10 ). Thus, pregnancy is a significant life event that is associated with the onset of chronic back pain in many young women.
A 2015 meta-analysis provided moderate-quality evidence that an 8- to 12-week exercise program during pregnancy, whether land- or water-based, reduced the number of women who reported back pain and functional impairment (relative risk [RR] 0.66; 95% confidence interval [CI], 0.45 to 0.97) and sick leave (RR 0.76; 95% CI, 0.62 to 0.94). Pain and functional disability were also reduced by a multimodal intervention that included exercise, manual therapy, and education. One small study evaluated the efficacy of transcutaneous electrical nerve stimulation (TENS) and found that it was associated with reduced pain and functional disability without adverse effects. The same study also showed a small effect for acetaminophen (paracetamol). In spite of their common use, little evidence exists to support the use of rigid pelvic support belts for the treatment of back pain. There is broad consensus that the use of imaging, rest, opioids, spinal injections, and surgery are inappropriately high in the general population. Despite emphasis on these modalities in recent years, there has been an increase in reports of back pain and disability. Use of these modalities is even less desirable during pregnancy because of the possible fetal exposure to potentially dangerous medications and ionizing radiation. More favorable outcomes are achieved through promotion of activity and function, including work participation.
Basic early management of low back pain does not differ from management in nonpregnant individuals, and includes biopsychosocial management and nonpharmacologic treatment (e.g., education supporting self-management, resumption of normal activities, and exercise). Psychological support programs and judicious pharmacologic intervention are indicated for those with persistent symptoms. Pharmacologic management of moderate to severe pain follows the World Health Organization (WHO) pain ladder ; acetaminophen and other nonopioid drugs (see later discussion) are the foundation of treatment, with supplementation by opioid analgesics as the second and third steps on the ladder.
Cauda equina syndrome and preexisting cancer are indications for immediate imaging and acute intervention. The benefits and risks of diagnostic imaging using modalities that expose the fetus to ionizing radiation should always be considered during pregnancy (see Chapter 17 ); however, magnetic resonance imaging (MRI) is considered safe and is useful for the diagnosis of acute back and pelvic pain in pregnancy. Advances are being made in ultrasonography for use in the diagnostic and therapeutic management of low back pain.
Pelvic Pain
Approximately 20% of women report pelvic pain during pregnancy. A long-term follow-up study found that 10% of women with pelvic girdle pain in pregnancy continued to suffer up to 10 years later. Thus, similar to other persistent pain conditions, pregnancy may be the condition that initiates long-term chronic pelvic pain. Pelvic pain can originate from various elements of the pelvic girdle, including the sacroiliac joints and pubic symphysis ( Fig. 42.2 ). These joints are stabilized by thick ligaments that usually do not allow much motion. Increasing estrogen and progesterone in pregnancy cause softening of the ligaments, allowing important skeletal reconfiguration to support the enlarging pregnancy and future delivery. Systematic review and meta-analysis of studies assessing physical exercise and manipulation found no benefit to these therapies for reduction in pelvic pain.
