Chronic Pain Issues After Cesarean Delivery

Ruth Landau

Introduction

In 1994, the International Association for the Study of Pain (IASP) defined pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”

Acute pain is defined as pain of short duration that is primarily caused by peripheral tissue injury. Chronic pain is empirically defined as pain lasting for an extended period of 3 months, or alternatively as persisting beyond the expected healing time. Substantial progress has occurred in the last decades in the understanding of the neurobiologic basis of clinical painful conditions. The distinctions between pain (a sensory and unpleasant experience) and noxious stimulus (an actually or potentially tissue-damaging event) were underlined in the IASP Basic Pain Terminology published by the IASP Task Force on Taxonomy (Table 14-1) (1).

“Real Women, Real Pain” was a campaign launched in 2007 by IASP to empower women and raise awareness of pain issues affecting women worldwide. That year (2007 to 2008) was declared the “Global Year Against Pain in Women.” Obstetric pain was reported as “pain related to childbirth that may present (a) during pregnancy, (b) during labor when more than 95% of women report pain, (c) occasionally during cesarean delivery if there is poor quality of nerve block or prolonged surgery, and (d) after delivery when more than 70% of mothers report acute or chronic pain.”

With over 4 million deliveries annually in the United States alone with a cesarean delivery rate above 30% (2), labor and delivery is likely to have a huge impact on the occurrence of acute pain and possibly chronic pain issues in the postpartum. Recent awareness that chronic pain may occur after childbirth has prompted clinicians and researchers to investigate this topic. Clearly, obstetric anesthesiologists have a unique opportunity to make a real difference in women’s experience of labor and delivery. With a constant increase in cesarean delivery rate and evidence that severe acute post-operative pain may result in chronic pain after surgery, obstetric anesthesia has to embrace its new role to provide optimal post-cesarean analgesia not only to improve short-term outcomes but also to prevent severe acute pain from becoming chronic and incapacitating in a constantly growing number of women.

In this chapter, a review of the vast body of knowledge accumulated in recent decades on chronic post-surgical pain, and more specifically the emerging concern that cesarean delivery may well be resulting in chronic pain in some women, as well as ways to predict and prevent this potentially devastating outcome are presented.

In order to treat something, we first must learn to recognize it.

—Sir William Osler

Chronic Pain After Surgery

The concept that tissue trauma from surgery could result in chronic pain was described approximately four decades ago. The first reports related to long-term phantom pain after limb amputations (3) and were followed shortly by publications on phantom breast pain after mastectomy (4), chronic pain post-thoracotomy (5,6), post-cholecystectomy (7), and postinguinal hernia repair (8). It became apparent in the mid-1990s that one in five patients referred to a chronic pain clinic implicated surgery as a cause of their chronic pain (9). Soon after, chronic post-surgical pain was recognized as an entity in its own (10,11,12). The incidence of chronic pain after surgery has been shown to depend on the surgical procedure and ranges between 4% and 50% (Table 14-2) (10).

The need for adequate pain control post-surgery was well established and “acute pain services” have thrived since the early 90s with the objective to reduce surgical stress, promote an early return to normal function, and improve overall post-surgical outcomes (13). The premise that acute post-operative pain may result in “wind-up” and pain hypersensitivity prompted anesthesiologists to offer preemptive analgesia and promote multi-modal strategies to enhance post-surgical analgesia (14,15). While there is overwhelming evidence that acute post-operative pain is associated with persistent pain and a high rate of chronic post-surgical pain, whether this describes a causal link or that individuals are simply more susceptible to develop both acute and chronic pain after surgery is still under investigation to this day. Management of acute post-operative pain in itself remains an ongoing challenge as it appears to be undermanaged (16). It has been proposed that applying procedure-specific analgesic recommendations may improve short and even long-term outcomes (17,18).

Definition of Chronic Post-surgical Pain

Several criteria (listed below) are required to meet the definition of chronic post-surgical pain so that preexisting pain that persists beyond the post-surgical recovery time is not misclassified as chronic post-surgical pain (19).

The pain developed after a surgical procedure
The pain has been lasting for at least 2 to 3 months
Other causes for the pain have been excluded (e.g., ongoing cancer pain, chronic infection)
The pain is not continuing from a preexisting painful condition (aggravation of pain attributed to the surgery is difficult to distinguish in this situation)

Table 14-1 IASP Basic Pain Terminology Published by the IASP Task Force on Taxonomy (1)

Pain		An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Allodynia*		Pain due to a stimulus that does not normally provoke pain.
Analgesia		Absence of pain in response to stimulation which would normally be painful.
Anesthesia dolorosa		Pain in an area or region which is anesthetic.
Causalgia		A syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes.
Central pain		Pain initiated or caused by a primary lesion or dysfunction in the central nervous system.
Dysesthesia		An unpleasant abnormal sensation, whether spontaneous or evoked.
Hyperalgesia*		Increased pain from a stimulus that normally provokes pain.
Hyperesthesia		Increased sensitivity to stimulation, excluding the special senses.
Hyperpathia		A painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold.
Hypoalgesia		Diminished pain in response to a normally painful stimulus.
The implications of some of the above definitions may be summarized for convenience as follows:
Allodynia Hyperalgesia Hyperpathia Hypoalgesia	Lowered threshold Increased response Raised threshold: Increased response Raised threshold: Lowered response	Stimulus and response mode differ Stimulus and response mode are the same Stimulus and response mode may be the same or different Stimulus and response mode are the same
Hypoesthesia		Decreased sensitivity to stimulation, excluding the special senses.
Neuralgia		Pain in the distribution of a nerve or nerves.
Neuritis		Inflammation of a nerve or nerves.
Neuropathic pain*		Pain caused by a lesion or disease of the somatosensory nervous system.
Central neuropathic pain*		Pain caused by a lesion or disease of the central somatosensory nervous system.
Peripheral neuropathic pain*		Pain caused by a lesion or disease of the peripheral somatosensory nervous system.
Neuropathy		A disturbance of function or pathologic change in a nerve: In one nerve, mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse and bilateral, polyneuropathy.
Nociception*		The neural process of encoding noxious stimuli.
Nociceptive neuron*		A central or peripheral neuron of the somatosensory nervous system that is capable of encoding noxious stimuli.
Nociceptive pain*		Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.
Nociceptive stimulus*		An actually or potentially tissue-damaging event transduced and encoded by nociceptors.
Nociceptor*		A high-threshold sensory receptor of the peripheral somatosensory nervous system that is capable of transducing and encoding noxious stimuli.
Noxious stimulus*		A stimulus that is damaging or threatens damage to normal tissues.
Pain threshold*		The minimum intensity of a stimulus that is perceived as painful.
Pain tolerance level*		The maximum intensity of a pain-producing stimulus that a subject is willing to accept in a given situation.
Paresthesia		An abnormal sensation, whether spontaneous or evoked.
Sensitization*		Increased responsiveness of nociceptive neurons to their normal input, and/or recruitment of a response to normally subthreshold inputs.
Central sensitization*		Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input.
Peripheral sensitization*		Increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields.
Note: An asterisk () indicates that the term is either newly introduced or the definition or accompanying note has been revised since the 1994 publication. Reprinted with permission from: “Part III: Pain Terms, A Current List with Definitions and Notes on Usage” (pp. 209–214) Classification of Chronic Pain, Second Edition, IASP Task Force on Taxonomy, edited by H. Merskey and N. Bogduk, IASP Press, Seattle, © 1994.

Table 14-2 Incidence of Chronic Pain After Surgery (10)

	Estimated Incidence of Chronic Pain	Estimated Disabling Chronic Pain (Pain Score above 5, on a Scale from 0–10)	US Surgical Volumes (1,000)
Amputation (phantom pain)	30–50%	5–10%	159 (lower limb only)
Breast surgery (lumpectomy and mastectomy)	20–30%	5–10%	479
Thoracotomy	30–40%	10%	N/A
Inguinal hernia repair	10%	2–4%	609
Coronary artery bypass surgery	30–50%	5–10%	598
C-section	10%	4%	1,400^a
^aEstimated volume in 2007. Reprinted from: Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: Risk factors and prevention. Lancet 2006;367:1618–1625, with permission from Elsevier.

Mechanisms Involved with the Development of Chronic Pain

Chronic post-surgical pain is similar to other chronic pain syndromes in that it is clearly multifactorial and complex. As emphasized above, it is considered as “abnormal” pain that persists beyond the expected time of healing. The current paradigm of chronic post-surgical pain emphasizes a transitional period during which acute pain evolves into chronic pain, or that individuals whose pain persists long term have inherent and/or induced deficiencies in endogenous pain inhibition that allow central sensitization to occur unopposed after injury.

Nociceptive pain refers to acute pain perception evoked by short-lasting noxious stimuli in intact tissue, in the absence of peripheral or central sensitization. Acute pain usually arises in response to activation of peripheral nociceptors, also called primary afferents. This “normal” or expected unpleasant sensation signals the presence, location, intensity and duration of a noxious stimulus and fades when the stimulus is removed. Nociception is a protective process that helps prevent injury by generating both a reflex withdrawal from the stimulus and a sensation so unpleasant that it results in complex behavioral strategies to avoid further contact with such stimuli. Sensitization of the nociceptive system is an additional phenomenon that occurs after repeated or particularly intense noxious stimuli, so that the threshold for its activation falls and responses to subsequent inputs are amplified. In the absence of ongoing tissue injury, this state of heightened sensitivity returns over time to the normal baseline.

With surgical trauma, besides the obvious nociceptive pain, inflammation and nerve injury also occur (Fig. 14-1). Ongoing inflammation and nerve damage are two factors that have been associated with hyperalgesia, central sensitization, and persistent pain.

Inflammatory pain refers to pain following tissue injury but with no neural injury. It results from the release of inflammatory mediators in response to tissue injury and inflammation. Peripheral sensitization occurs as sensitizing inflammatory mediators reduce the threshold of nociceptors that innervate the inflamed tissue. This hypersensitivity reduces the intensity of the peripheral stimulus needed to activate nociceptors at the site of inflammation and is called primary hyperalgesia. Peripheral sensitization is due to the reduction in threshold and enhanced responsiveness of nociceptors that occurs when the peripheral terminals of high-threshold primary sensory neurons are exposed to inflammatory mediators and damaged tissue. It is elicited by activation of nociceptors that play a major role in altered heat hypersensitivity and is restricted to the site of tissue injury. Central sensitization is an increase in the excitability of neurons within the central nervous system, so that normal inputs begin to produce abnormal responses. It results from changes in the properties of neurons in the central nervous system. The pain is no longer coupled to the presence, intensity, or duration of nociceptive stimuli. Instead, central sensitization represents an abnormal state of responsiveness or increased gain of the nociceptive system. Clinical manifestations of inflammatory pain often include spontaneous pain in the inflamed area, tactile allodynia, heat hyperalgesia, and throbbing pain. These exaggerated responses to normal sensory inputs usually outlast the tissue injury for hours and days but are usually reversible and normal sensitivity is eventually restored.

Neuropathic pain refers to pain after neural injury (peripheral or central). It is distinct from nociceptive and inflammatory pain conditions by the fact that the injury itself is neuronal. Neuropathic pain conditions are usually associated with abnormal neuronal activity at the site of injury as well as with central sensitization. A key feature of neuropathic pain is the combination of sensory loss with paradoxical hypersensitivity. Clinical features of neuropathic pain include hypoesthesia, dysesthesia, allodynia (often to cold), hyperalgesia, hyperpathia (bursts), and burning pain. The current paradigm is that not all patients with nerve damage will experience neuropathic pain. In some patients, the type of nerve injury may explain both the increase in acute pain and chronic pain, but the extent of pain will be mediated by other factors, including genetic, psychological, and physiologic factors that heighten pain sensitivity and impair pain modulation. It has been proposed that individuals whose pain persists long term have inherent and/or induced deficiencies in endogenous pain inhibition that allow central sensitization to occur unopposed very soon after the surgical injury. If that is the case, that would explain why examining pathways that inhibit pain, such as descending inhibitory pathways, could help predict patients with a higher risk for developing chronic post-surgical pain (20).

While it is a known phenomenon that stress induces analgesia, the opposite can also occur under particular condition, that is, non-painful stress can actually induce hyperalgesia. In a series of studies, Rivat et al. demonstrated in a rat model of pain that long-lasting hyperalgesia following inflammation or a surgical incision is enhanced by a single opioid dose (opioid-induced hyperalgesia); animals with inflammatory
pain experienced enhanced hyperalgesia in response to the same injury when this was repeated 1 week later (21). This exaggerated response was blocked by the administration of N-methyl-D-aspartate (NMDA) receptor antagonists (such as ketamine) indicating that opioid-induced hyperalgesia after inflammatory and surgical pain in rats treated with fentanyl is mediated by NMDA-dependent pro-nociceptive systems (21,22,23,24). Finally, rats exposed to inflammatory pain and/or opioid treatment in a repetitive manner (several weeks apart) as a model to explore opioid-induced hyperalgesia under non-naïve conditions (equivalent to “prior life events”) were shown to have persistent sensitization that was enhanced after each repeated 1 exposure to painful stimulation in opioid-exposed rats. That phenomenon was preventable by a single dose of NMDA antagonist such as ketamine (Fig. 14-2) (25).

Figure 14-1 Mechanisms of nociception-induced hyperalgesia (102).

The potential clinical relevance of these animal experiments is that repetitive exposure to post-operative pain
treated with opioids may well result in central sensitization and wound hyperalgesia with a growing number of surgical procedures. One could therefore speculate that chronic post-operative pain may actually occur in patients after a second painful “hit” rather than in opioid-naïve unsensitized patients. If these concepts are confirmed in humans, then repeat cesarean deliveries could be the ultimate model to replicate the conditions examined by Rivat et al in their rat model. This would set the basis for a theory whereby women may develop chronic pain only after their second cesarean delivery if hypersensitization and/or opioid-induced hyperalgesia occurred at the time of the first cesarean delivery.

Figure 14-2 Stress-induced hyperalgesia (21).

Chronic Pelvic Pain

Chronic pelvic pain is a common entity defined as non-menstrual pain in the lower abdomen present for at least 6 months (26,27). Gynecologic factors that have been associated with this disabling condition in women include endometriosis, intrapelvic adhesions, and chronic pelvic inflammatory disease. Diagnostic interventions often include a laparoscopy to identify anatomical anomalies, even though it is well known that pelvic anatomical anomalies do not necessarily cause pain. In particular, not all adhesions result in chronic pelvic pain. Neurologic factors have also been associated with chronic pelvic pain syndromes such as pudendal neuropathy and neuropathy secondary to the Pfannenstiel incision.

Almeida et al. were the first to report that a history of cesarean delivery may predispose to development of chronic pelvic pain (28). In a retrospective cohort study of Brazilian women scheduled to undergo a laparoscopy, findings in women with pelvic pain (n = 116) were compared to those of healthy women with no history of pain scheduled for a surgical tubal ligation (N = 83). A significantly higher proportion of women with a history of cesarean delivery was found in the group with chronic pain (67%) compared with the women in the control group (39%) (OR 3.7, 95% CI 1.7–7.7; p = 0.0006). Other predictors for chronic pelvic pain identified during the laparoscopy were the presence of endometriosis and sequelae of pelvic inflammatory disease. The presence of adhesions did not seem to be related with complaints of chronic pelvic pain.

Factors thought to be involved in the remodeling process that may cause pelvic adhesions include ischemia and an imbalance of proteolytic enzyme cells in the extracellular matrix (29). While pelvic surgery is associated with a very high occurrence of pelvic adhesions, it has been suggested that pregnancy may confer some protection from the risk of developing pelvic adhesions when compared to other gynecologic procedures, due to the increase in plasminogen activator activity that occurs in pregnancy (29).

Figure 14-3 Pfannenstiel incision.

Surgical Factors: Gynecologic and Obstetrical Procedures

The Pfannenstiel Incision

The Pfannenstiel incision was first described in 1900 by Hermann Johannes Pfannenstiel, a German gynecologist in a report on 51 cases (Fig. 14-3) (30). Advantages of this then novel surgical approach included the low incidence of incisional hernias and esthetical benefits (also called the “bikini-cut”). Nonetheless, chronic pain has been associated with entrapment of lower abdominal wall nerves and the Pfannenstiel incision as a surgical approach for gynecologic and cesarean delivery has now been acknowledged as a possible source of chronic pain (31,32,33,34).

In a series of studies, Brandsborg et al. reported that 5% to 32% of women suffer chronic pain after hysterectomy. Eleven studies were identified in a review of the literature evaluating studies that included the following keywords: Pain, chronic pain, pelvic pain, neuropathic pain, visceral pain, neuroplasticity, post-surgical, post-operative, gynecology, hysterectomy, Pfannenstiel, Joel-Cohen, vertical incision, nerve entrapment, incisional hernia, and incisional endometriosis (33). Pain as a preoperative symptom was present in 60% to 100% of women, and the pain prevalence 1 to 2 years after hysterectomy was 5% to 32%. Newly developed pain was reported in 1% to 15%, and exacerbated pain was found in 3% to 5% of women with preoperative pelvic pain. Factors reported to be associated with chronic pain included preoperative depression, preoperative pelvic pain, two or more pregnancies, previous cesarean delivery, and poor socio-economical status. The surgical approach (abdominal vs. vaginal or laparoscopy), incision type (vertical vs. Pfannenstiel), or anesthesia type (general vs. spinal) were not consistently associated with an increased risk for chronic post-hysterectomy pain. The authors suggest a list of parameters to enable comparisons between future studies and optimal assessment of chronic post-hysterectomy pain that include preoperative factors (indication for hysterectomy, previous pelvic disease/surgery, pain characteristics, analgesic consumption, psychological profiling and quantitative sensory testing, socio-demographics, genetics); intra- and early post-operative parameters (anesthesia, surgical procedure and complications, histopathology, acute post-operative pain and analgesic consumption); and post-operative parameters at more than 3 months post-hysterectomy (pain characteristics and analgesic consumption, post-operative complications including infection and reoperation, psychological profiling and quantitative sensory testing, and socio-demographics).

Brandsborg et al. as part of the Danish national audit to identify risk factors for chronic pain after hysterectomy contacted 1,299 women 1 year after surgery (32). Analysis was performed on a total of 1,135 women (87%) out of which 32% reported chronic pain and 23% had pain that affected daily activities. Only preoperative pelvic pain, pain as an indication for the surgery, previous cesarean delivery, and pain problems elsewhere were associated with a significantly increased risk for chronic post-hysterectomy pain. The surgical approach did not affect incidence of chronic pain but spinal anesthesia was associated with a reduced risk for chronic pain.

In a prospective manner, Brandsborg et al. enrolled 90 women scheduled to undergo hysterectomy. The women did not have endometriosis or malignancy. The main indications for hysterectomy were fibroids and abnormal uterine bleeding. The study sought to assess more specifically perioperative risk factors for the development of chronic pain (31). Preoperative pelvic pain (mostly localized to the middle of the pelvic area) was reported by 51% of women and 32% were taking analgesics. The attending gynecologist and anesthesiologist decided the surgical approach for hysterectomy and anesthesia mode, respectively. Abdominal approach (Joel-Cohen or Pfannenstiel) occurred in 63% of cases, vaginal approach occurred in 28%, and laparoscopic-assisted vaginal approach occurred in 9%. General anesthesia was conducted in 39% of cases, spinal anesthesia in 14%, and combined general–epidural anesthesia in 47%. Three weeks after surgery, pelvic pain was reported by 53% of women, and it was located at the level of the scar for 12% of them. Four months after surgery, 15 women (17%) still reported pelvic pain that affected their daily activities, and four women (4%) clearly stated that the pain was newly acquired and related to the surgery. Due to the small sample size, spinal anesthesia was not associated with a reduced risk for chronic pain as previously described by the same authors. This prospective longitudinal study is probably the only detailed report that avoided recall bias and allows differentiation of exacerbation of preexisting pelvic pain from new onset persistent post-surgical pain. The fact that only a relatively small proportion of women actually attributed their pelvic pain to the surgery itself sheds new insights into the incidence of chronic post-hysterectomy pain and associated risk factors. Preexisting pain and poor self-perceived control of pain along with acute post-operative pain were associated with persistent pain 4 months after hysterectomy rather than the surgical procedure itself. While nerve entrapment can occur with a Pfannenstiel incision, scar pain is unlikely to be a major contributor for persistent pain. This is consistent with the premise that abnormal pain modulation due to physiologic and psychosocial factors are involved in the development of chronic pain after hysterectomy as has been described for other surgical procedures as well.

In a survey to evaluate the prevalence and identify risk factors for post-Pfannenstiel pain syndromes, Loos et al. contacted 866 women who had a Pfannenstiel incision for either a hysterectomy (7%) or cesarean delivery (93%) in the previous 2 years (34). The Pfannenstiel incision was described to follow a standardized procedure that involved a 12 to 15 cm transverse incision approximately 2 to 3 cm cranial to the symphysis pubis with diathermal incision of subcutaneous fat and rectus sheath. If needed, the incision was extended laterally by cutting the fibrous sheath containing the aponeuroses of the external, internal oblique, and transverse abdominal muscles. The anterior fascia and linea alba was separated from underlying rectus and pyramidalis muscles over the entire distance between symphysis and umbilicus. Abdominal rectus muscles were then separated in the
midline, followed by division of the preperitoneal fat tissue and the opening of the peritoneum. No retractors were used. Once the abdominal procedure was completed, absorbable running sutures were used to approximate facial and muscle layers. The skin was closed intradermally. The questionnaire used to quantify and qualify pain was one used in several studies (see Appendix). It also included a schematic drawing on which women were instructed to mark the exact location of pain (Fig. 14-4). More than 90% of women described pain at the level of the incision, and in 70% the pain was at the lateral ends. Both neuropathic descriptors (“prickling” or “stabbing”) as well as non-neuropathic descriptors (“nagging” or “pulling”) were used in equal frequency to qualify the pain. Out of 690 responders (80%), 223 women (33%) stated that the incision site was still painful within the preceding month (median time from surgery was 26 months) with 9% reporting moderate to severe pain. Women with moderate or severe pain (n = 61) were invited for a follow-up at the institution’s outpatient clinic, and 32 women were extensively evaluated. Neuropathic pain caused by an entrapment of the iliohypogastric or ilioinguinal nerve was present in 17 women (53%). Nine women accepted a diagnostic nerve block that led to a significant pain reduction in six of them. The initial pain reduction persisted for at least 12 months in two of these six women. The remaining eight women refused injection. A diagnostic classification of chronic post-Pfannenstiel pain in these 32 women was presented. This finding suggests neuropathic pain in 53% of women, non-neuropathic non-gynecologic pain in 37% of women (diffuse scar pain in seven cases, musculotendinous pain in two cases, abdominal wall atrophy with bulging in one case, keloid in one case, fat necrosis in one case), and non-neuropathic gynecologic pain in 9% of women (endometriosis in one case, secondary vaginismus in one case, dysmenorrhea in one case). The incidence of nerve entrapment in women with moderate to severe pain was relatively high (17/32 women) but represented only a low occurrence within the entire cohort (less than 3%). Overall, numbness at the incision site, recurrent Pfannenstiel incisions, and emergency cesarean delivery were significant predictors for chronic post-Pfannenstiel pain. While length of incision did not as such predict chronic pain, a substantial proportion of women reported pain in the lateral portions of the scar. The innervating nerves of the suprapubic area and lower abdominal portions can be damaged or trapped when the incision is extended beyond lateral edges of the rectus sheath, and nerve entrapment was found to be common in women with moderate to severe pain.

Figure 14-4 Location of persistent pain after a Pfannenstiel incision (34).

Loos et al. also reported that neurectomy of the ilioinguinal and/or iliohypogastric nerve(s) provides good to excellent results in a series of 27 women (post-cesarean delivery in 19 of these cases) suffering from Pfannenstiel-induced neuralgic pain (35).

The Joel-Cohen Incision

The Joel-Cohen incision is a transverse skin incision that is placed about 3 cm below the line joining the anterior superior iliac spines, making it higher than the traditional Pfannenstiel incision. It has been proposed as a surgical approach to reduce surgical time and bleeding. However, its impact on infectious complications is still debated (36,37,38,39,40).

In a longitudinal prospective randomized clinical trial to compare the Joel-Cohen approach versus the Pfannenstiel approach for a primary cesarean delivery (mostly under general anesthesia), Nabhan et al. enrolled 600 Egyptian women. Sixty-two women in each group were further evaluated when a repeat cesarean delivery was scheduled (41). At the preoperative evaluation for the repeat cesarean delivery, four women in each group (7%) reported long-term pain. Patchy numb sensations were present in two women in the Joel-Cohen group and three women in the Pfannenstiel group. Intra-operative outcomes were significantly more complicated in the Pfannenstiel group, with a higher percentage of severe adhesions (bladder adherent to uterus) resulting in a longer surgical time and increased blood loss.

Options in surgical technique other than the abdominal skin incision type include blunt versus sharp abdominal entry, exteriorization of the uterus versus abdominal in situ repair, single- versus double-layer closure of the uterine incision, closure versus non-closure of the pelvic peritoneum, and liberal versus restricted use of a sub-rectus sheath drain. Studies assessing these surgical alternatives have evaluated primarily serious intra-operative and post-operative complications including organ damage, organ failure, significant sepsis, thromboembolism, high-care unit admission, blood loss, blood transfusion, and death (42,43,44,45,46). Evaluation of maternal satisfaction, pain outcomes, and analgesic use in the immediate postpartum are often scarce in these studies.

Peritoneal Closure

The benefits of closure versus non-closure of the visceral and/or parietal peritoneum to reduce pelvic adhesions have been evaluated in several studies and remain controversial (29,42,47). It has been suggested that more severe adhesions that require adhesiolysis prior to uterine incision occur more frequently when the peritoneum has been closed in a prior cesarean delivery (48). The impact of closure versus non-closure of the parietal peritoneum closure on severe acute post-operative pain (49,50) and chronic post-cesarean pain (51) has been evaluated.

Shahin et al. tested the hypothesis that non-closure of the parietal peritoneum would reduce the incidence of persistent post-cesarean pain (51). In a randomized clinical trial, Egyptian women were randomized to parietal peritoneum closure or non-closure during elective primary cesarean delivery under spinal anesthesia with hyperbaric bupivacaine (no opioid). In the closure group (n = 161), acute abdominal pain was present in 40% of women, with 29% of women reporting pain at 15 days postpartum and 25% reporting pain at 8 months postpartum. In the non-closure group (n = 16), only 18% reported severe acute pain, 12% at 15 days and 10% at 8 months. There was higher morphine consumption for management of acute post-operative pain in women in the
closure group. At 8 months, 14% of women in the closure group were taking analgesics compared to 4% in the non-closure group. When specifically assessing pain at the level of the incision, there was no difference at 8 months between the two groups; scar pain was present in 7% of women in the closure group and 2% of women in the non-closure group. Irrespective of surgical technique (and with no uterine exteriorization), this large prospective trial demonstrates that 18% of women report chronic abdominal pain at 8 months despite conventional multi-modal post-operative analgesia (NSAIDs, acetaminophen, and morphine for breakthrough pain). Better pain outcomes following peritoneal non-closure have been attributed to the rich nerve supply and poor blood supply of the peritoneum. Stretching, traction, suturing, and reapproximation of the peritoneum may cause ischemia which could explain high reports of visceral and epigastric pain.

Uterine Exteriorization

Uterine exteriorization is a common practice in North America and is thought to provide better exposure of the angles that may result in an easier and faster uterine closure, overall shorter surgical time, decreased blood loss, and decreased post-operative infection rate. It is important to note, however, that these purported advantages remain debated (52,53,54,55,56). Uterine exteriorization is also associated with increased intra-operative discomfort and pain (55,57,58), increased intra-operative nausea and vomiting (59), hemodynamic changes (59), and potentially fatal air embolism (60).

Nafisi et al. evaluated in a randomized clinical trial the effect of uterine exteriorization on acute post-operative pain in Iranian women who were scheduled for a cesarean delivery under general anesthesia (58). Visceral peritoneal closure was performed in all cases, and parietal peritoneal closure was performed in some cases (although which case and the proportion between the two groups were not specified). Ratings of visceral pain during the first two nights post-delivery and the number of women requiring supplemental opioids for breakthrough pain were significantly higher in women with uterine exteriorization (n = 102) versus women with in situ closure (n = 104). There was no difference in ratings of incisional pain between the two groups. Explanations for increased post-delivery pain with uterine exteriorization include peritoneal stretching. When added to that caused by parietal peritoneal closure, this factor may be consequential in this study.

Single-layer versus Double-layer Uterine Closure

Few studies have assessed this surgical parameter with pain outcomes after cesarean delivery. It has been suggested in one study that single-layer closure may marginally reduce the occurrence of severe post-operative pain on the first day post-delivery (61). On the other hand, this surgical technique may increase the risk for uterine rupture in subsequent pregnancies (62).

In summary, no study to date has been strictly designed to evaluate acute post-operative pain as a primary outcome combining all the various surgical options under optimal anesthesia. Nonetheless, surgical factors and the mechanisms whereby they appear to increase the likelihood for visceral pain, severe post-operative pain, and increased post-operative analgesic requirements include:

Larger surgical incisions (increases risk for lateral nerve entrapment and neuromas)
Uterine exteriorization (peritoneal stretching)
Parietal peritoneal closure (peritoneal stretching)
Repeated surgical procedure (hypersensitization)

Chronic Pain After Cesarean Delivery

Chronic pain after cesarean delivery has a definition similar to that of chronic pain occurring after other types of surgery (CPSP). Specifically, chronic pain after cesarean delivery has been defined as an abdominal wound scar pain persisting for more than 3 months after delivery and unrelated to menstrual pain. However, while CPSP has somewhat been recognized as an important and prevalent adverse outcome after surgery, chronic pain after cesarean delivery has only recently been considered as a possible entity (63).

Incidence: Myth or Reality?

Nikolajsen et al. published the first report on the incidence of chronic pain after cesarean delivery in 2004 in a cohort of Danish women (64). A questionnaire was sent within 6 to 18 months post-delivery to all women who had undergone an elective or unplanned cesarean delivery between October 1st 2001 and September 30th 2002. This was therefore a retrospective survey with a mean follow-up of 10 months. Two hundred and forty-four women were contacted, and the response rate was 90% (n = 220). Pain resolved in most women within 3 months. However, 19% of women reported that post-operative abdominal scar pain had lasted for more than 3 months, and at the time of the interview, pain was still present in 12% of women. Information about anesthetic technique and post-cesarean analgesia strategies (in particular, the administration of intrathecal morphine) was not provided. Several factors (i.e., previous abdominal surgery including cesarean delivery, presence of an indwelling epidural catheter for labor analgesia, indication for cesarean delivery [scheduled/unplanned], incision type, post-operative wound infection, maternal weight and height, and time of interview) were similar in women with and without chronic pain. Identified risk factors for persistent pain included general anesthesia, pain issues elsewhere, and recall of severe acute post-operative pain. This survey was important not only as the first study reporting on the incidence of chronic pain; it also provided a questionnaire (see Appendix) that has been utilized since then by other investigators in subsequent studies.

Eisenach et al. undertook a prospective longitudinal cohort study to describe the incidence of acute pain and chronic pain after delivery and possibly identify risk factors for the development of chronic pain (65). They enrolled 1,228 women who had delivered vaginally (n = 837), with or without neuraxial labor analgesia, as well as women who had undergone cesarean delivery (n = 391), either scheduled or unplanned (with or without a trial of labor). Unlike the previous report by Nikolajsen et al., women were questioned within 36 hours after delivery to assess for the presence of acute pain and to record preexisting pain, pain treatment before or during pregnancy, and degree of somatization using a 10-point scale (66). Delivery data including analgesic and anesthetic requirements were noted. At 8 weeks after delivery, the presence of persistent pain and its characteristics as well as features of postpartum depression based on the Edinburgh Postnatal Depression scale (67,68) were evaluated via phone interview. The major findings of this large prospective trial were that 20% of women after a cesarean delivery and 8% of women after a vaginal delivery reported severe acute pain in the immediate postpartum period that was associated with persistent pain and postpartum depression that had a significant impact on women’s ability to perform daily activities in the postpartum period. These observations stress the need for both better acute pain management at the time of delivery and studies that may help identify women at risk as well
as validate interventions that may reduce persistent pain and depression.

Sia et al. examined the incidence of chronic pain after cesarean delivery as an extension of their studies on acute post-cesarean analgesia, ethnicity, and genetic polymorphisms (69,70). In one study on the association between μ-opioid receptor genotype (OPRM1) and the clinical efficacy of intravenous morphine in 1,066 Asian women undergoing a cesarean delivery under spinal anesthesia with intrathecal morphine, 857 (80%) agreed to answer a survey that was based on Nikolajsen’s questionnaire (71). The median follow-up between the delivery and the phone interview was 14 months (12 to 20 months). The number of women reporting pain for more than 3 months but not present at the time of the survey was 28 (3%) and an additional 51 women (6%) reported pain still present at the time of the survey, resulting in a chronic pain rate of 9%. There was no association of chronic pain with the presence of other abdominal surgery or previous cesarean delivery, maternal age, gestational age, maternal weight or height, wound infection, duration of surgery, pain at 24 hours, or total morphine consumption post-cesarean. However, pain recall in the immediate post-operative period, pain present elsewhere (back pain and migraines most commonly), and non-private insurance were independent risk factors for the development of chronic pain. Since there was a higher recall of post-operative pain without a recorded difference in 24 hours post-cesarean pain scores or morphine consumption in women with chronic pain, this strongly suggested over reporting and recall bias; indeed some women were surveyed up to 20 months post-delivery. However, as noted by the authors, this could be a true effect as pain scores were not recorded beyond the first 24 hours post-cesarean and subsequent analgesia may have been ineffective.

In a second study by the same authors focusing on Chinese Han women, 631 women were enrolled for a genetic association study on polymorphisms of the ATP-binding cassette sub-family B member-1 (ABCB1) gene and acute and chronic pain after intrathecal morphine for cesarean delivery (72). Five hundred and three women (80%) agreed to take the Nikolajsen questionnaire. At 6 months post-delivery, 33% of women recalled wound pain at 1 month, 25% up to 3 months post-delivery, and 4% (20 women) between 3 and 6 months. Pain was still present at the time of the survey in 4% (18 women), with 1.2% (6 women) requiring analgesia for moderate to severe pain, and 0.6% (3 women) reporting daily pain. The incidence of chronic pain was 8%, which was essentially similar to the previous report by the same authors if one takes into account recall bias. The relatively low incidence of chronic pain in both reports in Asian women could be due to differences in ethnicity, genetics, and the surgical technique (no exteriorization of uterus and non-closure of peritoneum).

In a cohort of Finnish women, 600 consecutive mothers were surveyed within 12 months of their delivery to determine whether the incidence of persistent pain was more common after cesarean delivery than after vaginal birth (73). A sample size of 184 women per group would enable investigators to detect an increase in persistent pain from 5% after vaginal birth to 15% after cesarean delivery at a 0.05 significance level with 90% power. The response rate was 76% (n = 229) in the cesarean delivery group and 70% (n = 209) in the vaginal delivery group. Scheduled (37%) and unplanned cesarean deliveries (63%) were done under spinal anesthesia that contained morphine (120 to 160 μg), epidural anesthesia, or general anesthesia (14% of women). Labor epidural analgesia was provided to 66% of women with a vaginal delivery. Postpartum pain lasted significantly longer after cesarean delivery than after vaginal delivery; pain resolved by 2 months in 70% of women after cesarean delivery and 83% of women delivering vaginally. The major finding was that chronic pain was more frequent after cesarean delivery; pain at 12 months was reported by 18% of women after cesarean versus 10% after vaginal delivery (p = 0.011; odds ratio 2.1, 95% confidence interval 1.2 to 3.7). A trial of labor prior to cesarean delivery did not affect the incidence of chronic pain. Labor epidural analgesia did not affect the incidence of chronic pain in women delivering vaginally. While the intensity of the pain was rated overall as being mild in both groups, it affected daily life in 14% of women with a cesarean delivery and 15% of women delivering vaginally. Constant or daily pain at 12 months was present in 4% of women after cesarean delivery and in 1% of women with a vaginal delivery. Women with chronic pain at 12 months had a higher recall of pain in the first postpartum day regardless of mode of delivery and other risk factors included a history of chronic disease and previous pain (i.e., back pain).

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