Persistent pain after childbirth

Learning objectives.

By reading this article, you should be able to:

• •Identify factors contributing to the large variations in the estimated incidence of persistent pain after childbirth (PPAC).
• •Describe the significant impact of PPAC on maternal outcomes and quality of life.
• •Explain the proposed pathophysiology of PPAC and that the aetiology is still unclear.
• •Recall the biological, psychosocial, and peripartum factors associated with PPAC.

Key points.

• •Lack of consensus definition results in wide variation in the reported incidence of persistent pain after childbirth (PPAC).
• •PPAC has significant impact on maternal outcomes.
• •The pathophysiology of PPAC is uncertain because the available evidence is limited.
• •Biological, psychosocial, and peripartum factors have been associated with PPAC.

Introduction

Persistent pain after childbirth (PPAC) occurs in a significant proportion of postpartum women, and is an important societal and healthcare issue. Given that more than 140 million births occur annually, a large number of women are placed at risk of PPAC-related morbidity such as interference with activities of daily living and care of their newborn infant. In addition, PPAC may be associated with the development of postpartum depressive symptoms and increased healthcare utilisation. Until recently, PPAC has been an unrecognised morbidity of childbirth. One of the top research priorities in obstetric anaesthesia and perioperative medicine is to identify the risk factors contributing to PPAC to improve risk-stratification and pre-emptive interventions.

This review aims to provide a pragmatic overview of the difficulties in estimating the incidence, impact on maternal quality of life, proposed pathophysiological mechanisms underlying the transition from acute to persistent pain, and potential risk factors associated with PPAC. Furthermore, the association between severe acute postpartum pain and subsequent PPAC suggests that improving peri- and postpartum analgesia could potentially reduce the risk of PPAC. Clinical strategies to optimise analgesia after Caesarean section are discussed. It should be noted that a multitude of obstetric and non-obstetric pain conditions may be present after delivery and are beyond the scope of this review, which is limited to persistent postpartum pain associated with Caesarean and vaginal deliveries only.

Incidence and characteristics

The International Association for the Study of Pain (IASP) has recently proposed a definition of chronic post-surgical pain (CPSP) for inclusion in the International Classification of Diseases, 11th Revision (ICD-11) as pain that develops or increases in intensity after a surgical procedure or tissue injury, persists beyond the healing process of 3 months and is localised to the area of injury or referred to the innervation territory of a nerve situated in this area, with other causes of pain excluded.¹ However, inconsistency and lack of consensus in the definition of PPAC used in the literature have contributed to the wide variation in estimated incidence; scar pain after Caesarean section has been reported in 6.9–30.7% of women at 3 months and 1.9–19% at 6 months, whereas vaginal delivery was associated with perineal or vaginal pain in 1.3–48% of women at 6–8 weeks, 4.4%–55.7% at 3 months, and 2–6.4% at 6 months.²

The definition of PPAC used in previous studies varies in three main aspects. First, there is significant variation in the duration of postpartum pain that ranges from 2 months to more than 6 months after childbirth. Given that the incidence of PPAC generally decreases with time, it is vital to establish the minimum duration at which pain after childbirth should be considered PPAC.² Second, pregnancy is associated with a high prevalence of pain conditions such as pelvic pain, back pain and headache that may continue into the postpartum period,² and it may be challenging to differentiate pre-existing pain conditions from new onset pain. Based on a questionnaire administered between 6 and 18 months after Caesarean section, Nikolajsen and colleagues reported that 18.6% of women had abdominal wound pain lasting more than 3 months but did not differentiate pre-existing from new-onset pain.³ This may be especially relevant in the 16.8% and 32.3% of the study cohort who had previous abdominal surgery and Caesarean section, respectively. In comparison, Eisenach and colleagues reported a lower incidence of PPAC (9.8%) when only new onset pain at 8 weeks after vaginal or Caesarean section was considered.⁴ Third, it is important to specify which postpartum pain conditions are attributable to tissue injury during childbirth, and should therefore be considered PPAC. A prospective cohort study found abdominal scar pain in 9.2% of women at 3 months after Caesarean section, but also noted that pain at other locations was present in 68.4% of women not considered to have persistent pain.⁵ It is possible that inclusion of these pain conditions may result in a higher estimated incidence of PPAC. Furthermore, a significant proportion of postpartum women develop neuropathic pain, but there is no consensus on whether these cases should be considered PPAC. In a multicentre study investigating surgical site pain and neuropathic pain after Caesarean section at 3 months, only 6.6% of women had persistent surgical site pain whereas 21.4% were positive for neuropathic pain based on a modified Douleur Neuropathique-4 (DN4) questionnaire.⁶ Hence, whether neuropathic pain is included in the definition of PPAC will have a significant impact on its estimated incidence.

In addition, the estimated incidence of PPAC may be influenced by social and cultural barriers preventing women from reporting persistent pelvic pain or pain during sexual intercourse, or the belief that such conditions are normal after birth.⁷ Also, retrospective studies often rely on the mother's recollection of pain and its associated characteristics, and are therefore susceptible to recall bias. Therefore, to reduce conflicting information and improve comparability of data from various studies, a consensus definition of PPAC that clearly specifies the duration, onset and characteristics of persistent pain is required.

Clinical significance

Persistent pain after childbirth has a significant impact on maternal outcomes. Nikolajsen and colleagues investigated the effects of scar pain at 6–18 months after Caesarean section on mood, sleep and common daily activities and reported that 78% of women had pain when carrying heavy objects, 37% had pain with sports, 33% had significant mood changes and 30% had pain with stair climbing.³ When defined as new onset pain lasting at least 8 weeks after childbirth, pain adversely affected walking, sleep and mood in 40%, 36% and 19% of women after vaginal delivery, and 72%, 57% and 40% after Caesarean section, respectively.⁴ Similarly, 88% of women reported interference with carrying heavy objects, 53% with rising from a chair and 39% with standing and stair climbing because of scar pain after Caesarean section.⁵ Another study evaluated the impact of pain at 3, 6 and 12 months after Caesarean section using the Brief Pain Inventory, and found moderate to severe functional and quality of life impairment that were significantly correlated to pain intensity at all time points.⁸ In addition to its pain-related effects, PPAC has been associated with the development of symptoms of postpartum depression.⁴ PPAC is also likely to exert significant socioeconomic impacts although the magnitude is unclear.⁷

Proposed pathophysiology

Few studies have focused on elucidating the pathophysiology of PPAC, and high-quality evidence is lacking. It is also unclear if the mechanisms underlying PPAC are similar to those of other conditions causing CPSP, which are thought to involve the transition from acute to persistent pain through a complex and poorly understood process.⁹ In this paradigm, post-surgical pain is related to the nociceptive input resulting from tissue trauma, which is subsequently modified by peripheral and central sensitisation. It has been suggested that failure of this hyperalgesic state to resolve despite tissue healing and activation of antinociceptive mechanisms leads to the development of CPSP.

Chronic post-surgical pain results from a combination of nociceptive, inflammatory and neuropathic sources. Tissue injury stimulates nociceptor signalling and is exacerbated by the release of inflammatory factors and increase in nociceptor sensitivity. This phenomenon is known as primary hyperalgesia, and disproportionately increases nociceptive input transmitted to the CNS for a given level of stimulus.⁹ In addition, nerve injury may result in neuropathic pain that often clinically manifests as allodynia, hyperalgesia, hypaesthesia or dysaesthesia. Neuropathic pain may occur after Caesarean section as a result of the increased risk of ilioinguinal and iliohypogastric nerve entrapment associated with the Pfannenstiel incision.¹⁰

Sustained nociceptive input from nociceptive, inflammatory or neuropathic sources can invoke neuroplastic changes in primary afferent neurones within the dorsal root ganglia, termed peripheral sensitisation. This process involves changes in gene expression and long-lasting alteration of nociceptor sensitivity, tissue healing, remodelling and reinnervation. In turn, excessive peripheral nociceptive input may lead to neuroplastic changes in the CNS and development of central sensitisation; a form of spinal cord neuroplasticity that results in abnormal nociceptive responses which are decoupled from the presence or intensity of peripheral nociceptive stimuli.⁹

The transition from acute to persistent pain is also influenced by biological, psychosocial and peripartum factors via their effects on pain sensitivity and modulation.⁹ It was postulated that the presence of these factors may increase an individual's susceptibility to developing PPAC, and when incorporated into a risk-stratification model, may aid in the identification of patients at elevated risk of PPAC. Prior research has identified several risk factors associated with the development of PPAC (Table 1).

Table 1.

Risk factors associated with persistent pain after childbirth

Maternal factors	Surgical factors	Anaesthetic factors
Pre-existing pain conditions	Recurrent Pfannenstiel incision	Severity of postpartum pain
Depression	Parietal peritoneum closure	General anaesthesia
Psychological vulnerability
Stress
Pain catastrophising
Anxiety
Lack of private health insurance
Social deprivation
Genetic susceptibility

Associated factors

Pre-existing pain conditions

Pre-existing pain is an established risk factor for PPAC.² Nikolajsen and colleagues reported that pre-existing pain was present in 63% of women who developed persistent pain after Caesarean section, compared with 19% in women without PPAC.³ Pre-existing pain was independently associated with persistent pain after vaginal and Caesarean deliveries at 12 months.¹¹ Pre-existing pain also predicted the development of persistent pain after Caesarean section at 3 months, with back pain and migraine being the most common locations of pre-existing pain.⁵ Conversely, Eisenach and colleagues found no association between pre-existing pain and PPAC, although further analysis was precluded by the low incidence of PPAC in the study cohort.⁴

Psychosocial factors

Psychological and pain vulnerability factors may influence pain modulation and alter the risk of developing PPAC. Two systematic reviews on psychological predictors of CPSP reported that depression, psychological vulnerability, stress, pain catastrophising and anxiety were associated with CPSP.^12,13 Social factors such as the lack of private insurance and social deprivation were also reported to be significantly associated with PPAC, attributable to the lack of social support and access to medical care.⁵ However, an accurate and reliable risk-prediction model incorporating these factors has yet to be developed, and it is unclear if pre-emptive intervention targeting these risk factors will have significant effect on forestalling the development of PPAC or improving maternal outcomes.

Genetic factors

Limited data are available on the association between maternal genetics and PPAC risk, although a few gene polymorphisms have been investigated regarding their impact on acute pain after Caesarean section. For instance, a single nucleotide polymorphism (SNP) at position 118 of the mu opioid receptor gene-1 (OPRM-1), A118G, is associated with decreased opioid binding affinity and increased opioid requirements after surgery. A study in Asian patients showed increased 24 h systemic opioid requirements in women with the G118 allele after Caesarean section under spinal anaesthesia compared with those with AA118 homozygosity.¹⁴

The catechol-O-methyltransferase (COMT) enzyme is involved in catecholamine and oestrogen metabolism, and an amino acid substitution Val158Met is associated with reduced COMT enzyme activity and increased pain sensitivity. However, the Val158Met polymorphism did not significantly alter acute analgesic requirements after Caesarean section and the incidence of PPAC at 3 months.¹⁵

Factors related to surgery or tissue injury

Emergency Caesarean section has been postulated to increase the risk of PPAC, possibly because of the greater chance of iatrogenic nerve and tissue trauma, and the use of general anaesthesia, which may be less effective in blocking nociceptive input and central sensitisation compared with spinal anaesthesia. However, in some studies the urgency of Caesarean section has not been found to be a significant risk factor.^11,16 Furthermore, Nikolajsen and colleagues reported that a greater proportion of women with PPAC had received general anaesthesia (37%) compared with spinal anaesthesia (17%).³ However, a subsequent prospective study by Liu and colleagues showed no significant difference in PPAC risk associated with the use of either anaesthetic technique¹⁶.

Data regarding surgical technique and PPAC are limited. A systematic review found that the Pfannenstiel incision could result in ilioinguinal and iliohypogastric nerve injury and neuropathic pain.¹⁰ However, two studies comparing Pfannenstiel to vertical incisions found no significant difference in the risk of PPAC with either technique, although they were not primarily designed and powered to evaluate incision type as a risk factor.^3,11 Recurrent Pfannenstiel incision has been identified as a risk factor for PPAC, possibly because of the greater area of fibrosis that increases the risk of nerve entrapment.¹⁷ However, closure of the parietal peritoneum was reported to significantly increase the risk of both severe acute postpartum pain and PPAC at 8 months, compared with non-closure.¹⁸

In the context of vaginal delivery, increasing extent of perineal tissue injury is associated with severe acute postpartum pain, but not with PPAC. Macarthur and colleagues reported increased pain intensity and analgesia requirement within the first 7 days postpartum after perineal trauma or episiotomy, but found no significant difference in the incidence of PPAC at 6 weeks after first- or second-degree perineal injury, episiotomy, and third- or fourth-degree perineal injury.¹⁹

Acute postpartum pain

Severe acute pain in the postpartum period has been identified as a strong risk factor for PPAC.³ Severe acute postpartum pain was associated with 2.5-fold increased risk of PPAC at 8 weeks independent of the mode of delivery.⁴ Sng and colleagues reported that higher acute pain intensity after Caesarean section independently predicts PPAC at 3 months (odds ratio 1.3; 95% confidence interval 1.2–1.5).⁵ The mechanism underlying this association between severe postpartum pain and PPAC is unclear, and may be related to an individual's susceptibility to developing both acute and persistent pain, or that suboptimal analgesic management increases the risk of developing PPAC. Nonetheless, it should be noted that the association between severe acute postpartum pain and PPAC does not necessarily imply a causal relationship; it is possible that similar risk factors exist for both acute pain and PPAC, hence women possessing these risk factors may be susceptible to both conditions.

Oxytocin

Experimental studies in animals that induced pain hypersensitivity by spinal nerve ligation suggest that increasing concentrations of oxytocin during labour and lactation may protect against PPAC. The evidence for this is: (1) spinal oxytocin concentrations were increased in postpartum rats compared with non-pregnant controls; (2) weaning of the pups and reduction in oxytocin concentrations led to increased hypersensitivity; and (3) intrathecal oxytocin reduced hypersensitivity, and this was attenuated by atosiban (an oxytocin receptor antagonist).²⁰ Nonetheless, human studies are limited and further investigations into the physiological mechanisms and therapeutic application of oxytocin in the context of PPAC are warranted.

Prevention

Theoretically, identifying women at greater risk of developing PPAC will facilitate individualised and preventive clinical management. Yet, despite the recognition of several factors associated with PPAC, the development of a robust risk-stratification model remains elusive, and there is scarce evidence that pre-emptive treatment targeting known risk factors significantly reduces its risk and incidence of adverse outcomes.

For example, the association between severe acute postpartum pain and PPAC suggests that optimising postpartum analgesia could potentially reduce the risk of PPAC.⁴ However, most studies investigated the efficacy of perioperative analgesics on reducing acute pain after Caesarean section, and it is uncertain if improving postpartum analgesia will have significant impact on the risk of developing persistent pain after Caesarean or vaginal delivery. Furthermore, the use of analgesics should be balanced against concerns of drug transfer via breast milk and the possibility of opioid-related morbidity. Nonetheless, inadequate analgesia may result in delayed functional recovery, impaired maternal–fetal bonding and increased risk of postpartum depressive symptoms, and should therefore be a priority for peripartum anaesthetic management.²¹

Neuraxial anaesthesia is the technique of choice for Caesarean section as it reduces maternal and fetal morbidity compared with general anaesthesia. Neuraxial anaesthesia often combines local anaesthetic with lipophilic opioids such as fentanyl and longer-lasting hydrophilic opioids such as morphine. Long-acting neuraxial opioids improve analgesia and reduce sedation compared with systemic opioids. Because of the analgesic ceiling effects and dose-dependent increase in adverse effects, the optimal dose of intrathecal morphine is 50–100 μg, or 2–4 mg when given via the epidural route.²¹ Neuraxial anaesthesia is often supplemented with a multimodal regimen to reduce opioid consumption, and should consist of oral paracetamol and NSAIDs at scheduled regular intervals. Because the analgesic effects of paracetamol and NSAIDs are synergistic, they should be given on a scheduled basis as this further improves analgesia and decreases opioid consumption, nausea and vomiting compared with as-needed regimens. Pain not responding to this regimen can be managed with oral opioids as needed, with intravenous opioids reserved for women in extreme pain or intolerant of oral medications.²¹

Other analgesic adjuncts have been evaluated in the context of reducing acute pain after Caesarean section, but careful consideration of risks and benefits are required given the conflicting evidence available on their analgesic benefits and increased risk of adverse effects. For instance, gabapentinoids reduced 24 h pain scores in one study but others found no analgesic benefits compared with placebo.²¹ In another study there was no significant difference in the incidence of PPAC between a single perioperative gabapentin dose and placebo.²² Conversely, ketamine has been shown to reduce cumulative morphine consumption and increase time to request for analgesia request compared with placebo in women receiving neuraxial anaesthesia for Caesarean section.²³ Although ketamine was not found to reduce PPAC after Caesarean section, S-ketamine may attenuate hyperalgesia at 12 and 24 h after Caesarean section.²⁴ Finally, the role of perioperative clonidine in reducing PPAC is unclear; Lavand'homme and colleagues reported that intrathecal clonidine reduced incisional hyperalgesia at 48 h after Caesarean section, but without change in the incidence of PPAC at 6 months.²⁵

Summary

Persistent pain after childbirth occurs in 0.3–55% of postpartum women, with this wide incidence attributable to the lack of a consensus definition. It has a significant impact on maternal quality of life, is associated with postpartum depressive symptoms and may increase healthcare utilisation. Few studies have investigated the pathophysiology of PPAC, and it is uncertain whether PPAC has a similar aetiology to other forms of persistent pain. Increased peri- and postpartum concentrations of oxytocin may have protective effects against PPAC, but it is yet unclear how this may be used to reduce or treat PPAC. Conversely, pre-existing pain conditions, severe postpartum pain, maternal genetics and psychosocial factors such as depression, psychological vulnerability, stress, pain catastrophising, anxiety and social deprivation are potential risk factors for PPAC. In addition, recurrent Pfannenstiel incision and closure of the parietal peritoneum may be associated with increased incidence of PPAC. Given that severe acute postpartum pain is a consistent predictor of PPAC, it was hypothesised that providing appropriate analgesia may reduce PPAC, although this should be verified in future research. In addition, a consensus definition of PPAC that specifies the minimum duration, onset and characteristics of persistent pain is required, and further research is necessary to develop risk-stratification models to identify patients at increased risk of developing PPAC as this may facilitate early surveillance and intervention.

Declaration of interests

The authors declare that they have no conflicts of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Hon Sen TanMD MMed (Anaesthesiology) MHSc is an associated consultant at KK Women's and Children's Hospital. His major clinical and research interests include persistent pain, and the use of medical devices to improve pain and haemodynamic management.

Ban Leong SngMMed (Anaesthesiology), FANZCA, FFPMANZCA, MCI, FAMS is a senior consultant and head of the Department of Women's Anaesthesia at KK Women's and Children's Hospital. He is also an associate professor at Duke–NUS Medical School. His major clinical and research interests include persistent pain, and the impact of maternal pain and psychological risk factors on acute and persistent pain.

Matrix codes: 1H02, 2E03, 3B00, 3E00