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Pathogenesis
Treatment
During pregnancy there is increased ligamentous laxity,36
Behavioral interventions
thought to be due to hormonal influence (estrogen and relaxin).37
Behavioral interventions may reduce analgesic drug requirements.
Changes in the three-dimensional alignment of the normal spine
As pregnant women are highly motivated to avoid medications
as pregnancy progresses, coupled to normal weight gain, increase
this type of intervention is more likely to be acceptable during
the mechanical strain on muscles, ligaments, and disc structures
pregnancy. Three types of nonpharmacological interventions are
of the spinal column.32 This leads to muscle fatigue and soft tissue
frequently used: relaxation training, thermal biofeedback, and
strain, which generates pain.32 When this derangement is severe
stress-management therapy.24 Holroyd et al. compared a relaxa-
enough to impair normal daily function because of pain or pelvic
tion/biofeedback technique to propranolol therapy using a meta
instability, it is referred to as symptom-giving pelvic girdle relaxa-
analysis. They found a 43% reduction in migraine headache activity
tion.38 Differential diagnoses include lumbar disc herniation,
in the study groups, with no improvement in controls (no therapy),
spondylolisthesis,39 and infectious sacroiliitis.40
and only a 14% improvement in the placebo group.25 During preg-
nancy, Marcus et al. showed that relaxation coupled to thermal
biofeedback provided a clinically significant improvement in head-
Clinical symptoms
ache activity in 73% of women compared to 29% in a control group.26
Moreover, the beneficial effect of behavioral therapy is maintained in The usual complaint is posterior or low back pain, aggravated by
nearly two-thirds of women up to one year postpartum.27 activity and usually relieved by lying down or sitting. Often it is
described as persistent and not very severe.39 Patients can have
Pharmacological interventions complaints of pain above the lumbar region, in the lumbar region
with or without radiation to the thighs or over the sacroiliac joint
Treatment of headache during pregnancy and the postpartum
area, sometimes radiating to the buttocks and posterior thighs
period is challenging, because few data are available about the



230
Chapter 12




Figure 12.2 Pathophysiology of migraine. Migraine involves dysfunction of brain-stem pathways that normally modulate sensory input. The key pathways for the
pain are the trigeminovascular input from the meningeal vessels, which passes through the trigeminal ganglion and synapses on second-order neurons in the
trigeminocervical complex. These neurons, in turn, project through the quintothalamic tract, and after decussating in the brain stem, form synapses with neurons in
the thalamus. There is a reflex connection between neurons in the pons in the superior salivatory nucleus, which results in a cranial parasympathetic outflow that is
mediated through the pterygopalatine, otic, and carotid ganglia. This trigeminal-autonomic reflex is present in normal persons34 and is expressed most strongly in
patients with trigeminal-autonomic cephalgias, such as cluster headache and paroxysmal hemicrania; it may be active in migraine. Brain imaging studies suggest
that important modulation of the trigeminovascular nociceptive input comes from the dorsal raphe nucleus, locus ceruleus, and nucleus raphe magnus. From Goadsby,
P. J. et al.22 with permission.



Pubic pain
(but usually not in a sciatic distribution). This latter form is often
accompanied by symphysis pubis pain.33
Some pregnant women experience severe pelvic pain in the pubic
symphysis joint, which often worsens with subsequent pregnan-
Treatment
cies and may persist for years.38 Prevalence rates of symphyseal
pain with onset during pregnancy increases from 1.5% in week 12,
The primary treatment is prevention. It has been suggested that
to 6.4% in week 24, and 20.0% in week 36, while sacral pain is
good physical fitness prior to pregnancy reduces the risk of back
pain in a subsequent pregnancy.32,41 During pregnancy, once around 10% at the end of the first trimester, increasing and
stabilizing at nearly 25% in the second and third trimesters.34
the acute pain subsides, an exercise program to increase spinal
Ligamentous laxity occurs during pregnancy.39 MacLennan et al.
and abdominal muscle strength can help reduce the continued
symptoms of back pain.39 The main focus of treatment is to identified an association between high serum relaxin levels and
pelvic pain associated with joint laxity during late pregnancy, with
reduce the workload of the pelvic girdle and low back by redu-
a prognostic correlation between relaxin levels and intensity of
cing physical activity, avoiding stair climbing, and the use of
pain.37 However, some patients may have high levels of circulating
extreme range of motion in the hips or the back.35 In addition,
relaxin and be asymptomatic, suggesting that peripheral relaxin
the use of a nonelastic pelvic support reduces pain in more than
levels may not be as important as relaxin receptor levels,37 or that
80% of women with posterior pelvic pain.41 Drug therapy is
there is no exclusive relationship between the hormone and the
usually restricted to acetaminophen and NSAIDs. Surgery is
symptoms, as some have suggested.36,42,43,44 What seems to be
seldom required, unless a structural anomaly and neurological
consistent is the relationship of symphyseal distention and pain.45
compromise is present.



231
3 Nervous system disorders


confirmed the correlation between edema and neurophysiologic
Table 12.1 Suggested drugs and dosages for prevention and behavior in CTS with the clinical finding of edema being diag-
treatment of headache during pregnancy.15,22,54 nostic and predictive of CTS, as well as a marker of severity of
symptoms.52 Furthermore, it has been suggested that smoking
Preventive therapy
and alcohol consumption may have a negative role in the devel-
Drug Dose
opment of CTS: probably due to impairment of the microcircula-
Propranolol 40“120 mg q12h po
tion of the hand, providing a negative contribution to the
Metoprolol 100“200 mg qd po
evolution of the syndrome.52
Atenolol 25“100 mg qd po
Amitriptyline 10“75 mg qhs po

Prognosis
Treatment
Drug Dose
Approximately 50% of women will have persistence of symptoms
Acetaminophen 1 g q6h max po
one year postpartum; however, most report an improvement in
Caffeine 100“200 mg po
their symptoms.55 Patients with early onset of CTS symptoms as
500 mg i.v.
well as excessive weight gain during pregnancy are less likely to
Ibuprofen 400“800 mg q8h po
improve postpartum.55 Some authors suggest that women with
Naproxen 500“1000 mg q8h po
CTS during pregnancy have a higher risk of developing this con-
Sumatriptan 50“100 mg q12h po
dition later in life,53 supporting the concept that poorly treated
5“20 mg q12h nasal
pain can lead to neuropathic chronic pain.5
6 mg s.c.
Meperidine 25“100 mg q6h i.v.
Treatment
Fentanyl 25“50 mg q6h i.v.

In identified cases, most clinicians are reluctant to recommend
qhs ¼ quaque hora somni; po ¼ per os; qd ¼ once a day
carpal tunnel decompression during pregnancy even when
i.v. ¼ intravenous; s.c. ¼ subcutaneous
symptoms are severe,56 since a high percentage of patients with
CTS symptoms will resolve spontaneously after delivery. Thus,
The symphysis pubis is a nonsynovial joint at the confluence of
conservative measures are the mainstay of treatment during
the pubic bones that is joined by intrapubic, fibrocartilagenous
pregnancy.57 Supportive and conservative therapies usually are
tissue.46 Widening of the symphysis pubis can cause tenderness
indicated for patients who are sufficiently symptomatic. 53 Wrist
that is usually aggravated by exercise. Rupture of the symphysis
splints placed on the dorsum of the hand, which keep the wrist in
pubis (diastasis pubis) is an uncommon event. However, there is
a neutral position and maximize the capacity of the carpal tunnel,
a report of spontaneous pubic separation that was diagnosed
often provide dramatic relief.54 Wrist immobilization has been
after a laboring patient developed pubic pain under continuous
combined with dietary salt reduction, with excellent improve-
epidural analgesia.47
ment in clinical and electrophysiological assessments.57 Some
authors advocate the use of hydrocortisone injections in the
Treatment carpal tunnel, since over 65% of all CTS are derived from non-
specific synovial edema.58 The benefits of other treatments
If separation is less than 1 cm, treatment is supportive with rest
(diuretics and NSAIDs) are, to date, inconclusive.
and conservative measures such as an ice pack. There may be
Surgical correction is recommended for patients with early
some benefit from local anesthetic injections; however, their
onset of CTS, severe symptoms, or severe neurophysiologic
effect appears to be short lived.48 For separations greater than
impairment with deteriorating muscle tone and motor function
1 cm (criteria for diagnosis of pelvic instability),45 treatment, such
despite conservative measures.58
as reduction with tight pelvic binding, lateral decubitus position
with absolute bed rest and NSAIDs, is indicated.39,47 Surgical
treatment may be considered in patients who have inadequate Fibromyalgia
reduction, persistent symptoms, or recurrent diastasis.47
Fibromyalgia is a multisymptomatic syndrome defined by the
core features of chronic widespread pain, exquisite tenderness
Carpal tunnel syndrome
at multiple anatomical sites, and other clinical manifestations
Disregarding back pain, carpal tunnel syndrome (CTS) is the most such as severe fatigue, sleep disturbances, and associated symp-
frequent musculoskeletal complaint in pregnancy. Depending on toms related to visceral hyperalgesia (irritable bowel and blad-
der).59,60 The overall prevalence is about 2“3%,59,61 with a female
the study design, definitions employed and sensitivity of the diag-
predominance of approximately 8:1.62 Fibromyalgia is more com-
nostic tests applied in different series the incidence ranges up to
62%.49,50,51,52 Neurophysiological evaluation reveals nerve dys- mon in Caucasians and can occur in younger women at an age
function in nearly half of the women with clinical symptoms.52 when they are more likely to be fertile.59,61
Many authors consistently have reported a correlation between Although the pathophysiology underlying this syndrome is
edema in pregnancy and CTS symptoms.49,50,53,54 Padua et al. unknown, contemporary research has pointed to genetic factors,



232
Chapter 12


combined with abnormal peripheral and central pain mechan-
Table 12.2 FDA pregnancy categories
isms (central sensitization).59 Among factors associated with
symptom onset are: infectious illnesses, physical or emotional FDA pregnancy categories
trauma, and stress.59
Pregnancy Definition
On examination, patients with fibromyalgia have typical paired
category
tender points. These exquisitely tender points are generally sym-
A Controlled studies in pregnant women fail to
metric and are located at the occiput, trapezius, neck, anterior chest
demonstrate a risk to the fetus in the first trimester
wall, epicondyle, low back, trochanteric region of the hips, and
with no evidence of risk in later trimesters. The
medial aspect of the knees bilaterally.63 Other than these tender
possibility of fetal harm appears remote.
points, the remainder of the musculoskeletal examination in fibro-
B Either animal-reproduction studies have not
myalgia is usually normal. There are no specific abnormal labora-
demonstrated a fetal risk but there are no
tory results associated with fibromyalgia, so diagnosis is established
controlled studies in pregnant women, or animal-
from the clinical features.64 The diagnostic criteria are: (1) wide-
reproduction studies have shown an adverse effect
spread pain for at least three months in combination with (2) pain
(other than a decrease in fertility) that was not
on palpation at 11 or more of the 18 specific tender point sites.65
confirmed in controlled studies in women in the
Fibromyalgia during pregnancy has not been well documented
first trimester and there is no evidence of a risk in
and few studies have focused on the natural history of fibromyalgia
later trimesters.
and pregnancy.66,67 Ostensen et al. performed a prospective,
C Either studies in animals have revealed adverse
observational study of 50 women allocated to one of two groups:
effects on the fetus (teratogenic or embryocidal
women who had delivered a child while suffering from fibromyal-
effects or other) and there are no controlled studies
gia or controls, who were women who had their children before
in women, or studies in women and animals are not
the onset of fibromyalgia.67 The symptoms reported by the first
available. Drugs should be given only if the
group (pregnant women with fibromyalgia) were generalized fati-
potential benefits justify the potential risk to the
gue, back pain, muscle weakness, depression, and stiffness. These
fetus.
women also complained of aggravation of symptoms about one to
D There is positive evidence of human fetal risk, but the
three months postpartum and reduced capacity to look after their
benefits to treat serious disease in pregnant women
babies. Despite this, most women found pregnancy a positive
may be acceptable despite the risk (e.g. if the drug is
experience. Those women who experienced multiple pregnancies
needed in a life-threatening situation or for a
did not describe any increase in the severity of symptoms in sub-
serious disease for which safer drugs cannot be
sequent pregnancies, compared to the first one. Women with
used or are ineffective.
fibromyalgia gave birth to healthy, full term babies, with no differ-
X Studies in animals or human beings have
ence in obstetrical outcome compared to the controls. Nearly all
demonstrated fetal abnormalities or there is
women described worsening symptoms of fibromyalgia during
evidence of fetal risk based on human experience,
pregnancy, with the third trimester the worst, as well as increased
or both, and the risk of the use of the drug in
functional impairment and disability postpartum.67
pregnant women clearly outweighs any possible
benefit. The drug is contraindicated in women who
Treatment are or may become pregnant.

Treatment of fibromyalgia involves a multimodal regimen that Data from reference28 and www.perinatology.com/exposures/Drugs/
includes patient education, cognitive behavioral therapy, gentle FDACategories.htm
exercise, and medications to help with sleep and pain,68 plus
antidepressants.69 Although initial descriptions of outcomes
after multimodal treatment were encouraging and optimistic,66 treated by stretching, improved physical conditioning, acupres-
sure, and physician intervention with trigger point injections of
recent reports suggest that this syndrome is often unresponsive to
local anesthetics60 or local anesthetics mixed with corticoster-
therapy70 and has a poor prognosis.69 With that in mind, the
oids.69 Nonsteroidal anti-inflammatory drugs are usually ineffec-
pharmacological management of pain in fibromyalgia should
tive for this condition.71
focus on the major sites of pain processing: namely peripheral
The modulation of central sensitization is mainly pharmacolo-
pain generation, dorsal horn sensitization, psychological influ-
ences, and the descending pain pathways.60 gic. Currently the only drugs approved by the FDA that modulate
central reactivity are those that activate or amplify the descending
There is no specific tissue pathology characteristic of fibro-
pain pathways. These medications include tricyclic antidepres-
myalgia, at least in peripheral tissues. However, the central ner-
sants, opioids, and a2-adrenergic agonists.60 Low-dose tricyclic
vous system (CNS) is sensitized, so peripheral pain generators are
antidepressants, such as amitriptyline 10 to 25 mg taken at bed-
not only perceived as being more painful but they also prolong
time, are generally considered the treatment of choice in fibro-
and amplify the machinery of central sensitization. The most
myalgia.64 Tricyclic antidepressants are FDA pregnancy category
common pain generators in fibromyalgia patients are myofascial
C drugs (see Table 12.2) and are considered probably safe in
trigger points. These trigger points need to be identified and



233
3 Nervous system disorders


pregnancy and lactation.28 However, despite their widespread of neuropathic chronic pain is known to be high after specific
use only 25 to 30% of patients improve and the long-term efficacy operations such as limb amputations, thoracotomies, and mas-
is not sustained.60,72 Opioids are used often in the treatment of tectomies, with incidences ranging from 5 to 80%.79 However,
fibromyalgia, but there have been no controlled clinical trials of little is known about the incidence after cesarean section. In
their effectiveness. Opioids should not be the first analgesic a prospective observational study over a one-year period
choice, but they should not be withheld if less powerful analgesics Nikolajsen et al. evaluated more than 200 patients who under-
have failed.60 Tramadol, an FDA pregnancy category C drug,28 is a went cesarean section using a low transverse incision.80 They
weak opioid with a low side effect profile that has gained attention found that pain lasted more than three months in 18.6% of
in the treatment of fibromyalgia. Initial trials using a single intra- patients, while 12.4% had persistent pain after ten months.
venous dose of tramadol 100 mg showed a 20% reduction in Among patients with persistent pain, there was a greater propor-
spontaneous pain compared to baseline and a 40% improvement tion who had received general anesthesia compared to subarach-
over the placebo group.73 In another study, the combination of noid anesthesia for their procedure, suggesting a protective or
tramadol and acetaminophen proved moderately effective, com- preemptive role of neuraxial anesthesia in the development of
pared to placebo.74 At present, there are no reports of tramadol chronic pain. This finding mimicked the results of two other
treatment of fibromyalgia during pregnancy. a2-Adrenergic ago- studies of chronic pain following thoracotomy and prostatect-
nists such as tizanidine (FDA pregnancy category C)28 have been omy.81,82 It may be speculated that noxious input to the CNS is
used successfully in some chronic pain disorders; however, there less during spinal anesthesia than during general anesthesia.
have been no controlled trials in fibromyalgia.60 There is evi- Experimental and clinical studies have shown that an afferent
dence, in the experimental setting, that blocking N-methyl barrage of noxious input can generate a central sensitization in
D-aspartic acid (NMDA) receptors with ketamine75 and/or dex- second order noxious responding neurons and that such central
tromethorphan ameliorates pain in fibromyalgia subjects.60 sensitization may be associated with an increased risk of persis-
tent pain.80
The severity of postoperative pain is a potent predictor of sub-
Nonpharmacologic treatment
sequent chronic pain;5 however, this has not been well investi-
Multidisciplinary treatment of musculoskeletal disorders that gated. In a prospective study of 100 patients Lavand™ homme et al.
includes physical rehabilitation and psychological, behavioral, found a chronic pain incidence of 14.8% six months after cesar-
and educational interventions has gained interest. 70,72 In addi- ean section. Previous genitourinary tract infection and higher
tion to some evidence of efficacy, this treatment also demon- postoperative pain (characterized by wound hyperalgesia) were
strates a cost-effective profile, which makes it plausible to be risk factors for developing chronic pain, probably in relation to
central sensitization.83 Finally, Luijendijk et al. found that the size
used for long-term treatment in the average patient. 70 Some
studies suggest that a structured exercise program that empha- of the surgical incision is strongly related to the risk of postopera-
sizes aerobic fitness training produces significant and sustained tive chronic pain, possibly due to nerve entrapment, neuroma
improvements in these patients,59 while others have found no formation, or skin numbness84 (which can be interpreted as
benefits from this approach.69,76 pain).


Pain in the postpartum period Treatment
Postpartum pain is often referred to as lower abdominal ˜˜after Postoperative pain intensity and extent of tissue damage (includ-
pains,™™ which are perceived centrally in a recurrent fashion with ing length of the surgical incision) are two of the factors that have
an intensity that can be severe.13 Murray et al. found that post- been directly linked to postoperative chronic pain.79 With this in
partum abdominal pain was greater in multiparous than primi- mind, aggressive postoperative analgesia should be implemented
parous women.77 Holdcoft et al. confirmed that the intensity of as soon as possible, ideally in a preemptive fashion. However, this
˜˜after pains™™ increased significantly with parity, and that parity has not been found effective in the short term. Huffnagle et al.
also increased the number of pain sites.78 This increase in pain performed bilateral iliohypogastric-ilioinguinal blocks with local
with subsequent pregnancies supports the concept of plasticity anesthetics prior to the surgical incision for cesarean section and
found no benefit.85 Others have shown encouraging good results
whereby a previous painful event provokes changes in the chem-
ical milieu in the spinal cord and triggers structural reorganiza- by using multimodal preincisional treatment for hernia repair
tion,3 leading to an enhanced response on a subsequent painful surgery. This treatment included systemic NSAIDs and NMDA
insult. inhibitors, ketamine, and local anesthetic infiltration of the inci-
sion site.86 Others have shown that ketamine infiltration of the
area of hyperalgesia around the incision reduced the incidence of
Chronic postcesarean section pain
residual pain up to six months after surgery.87 This finding sug-
Persistent pain after surgery, also referred to as chronic postsur- gests that blocking the NMDA receptors is beneficial for long-
gical pain syndrome, is defined as the presence of pain that term pain control, but also that the presence of hyperalgesia (a
persists for more than three months after surgery, excluding the marker of central sensitization) could predict the development of
preoperative condition and other causes of pain.79 The incidence persistent pain after surgery.87 Therefore a preemptive effect is



234
Chapter 12


most likely produced at the level of central sensitization rather lower ribs and it interfered with daily living and night sleep.
Injection of bupivacaine 0.5% and triamcinolone48 completely
than at a local site. Even if a preemptive mechanism is not
demonstrated for ongoing pain control this approach is well relieved the pain. Others recommend epidural analgesia for preg-
nancy-induced intercostal neuralgia.91
supported from a humanitarian point of view.
As these patients are young women in charge of babies and Meralgia paresthetica is a symptom complex that includes
numbness, paresthesiae, and pain in the anterolateral thigh.92
young children, nonsystemic therapy is favored, whenever possi-
ble, in order to reduce the side effects related to systemic admin- The most likely etiology in pregnancy is entrapment of the lateral
istration of analgesics and adjuvant drugs. Some authors cutaneous nerve as it passes around the anterior superior iliac
recommend local infiltration of the scar,48 especially at the most spine or through the inguinal ligament. Onset of symptoms, most
sensitive place (trigger point) with the long-acting local anes- commonly numbness on the anterolateral thigh, but possibly
thetics bupivacaine or levobupivacaine 40 to 50 mg combined burning, tingling, and other paresthesiae, can occur at any time
with methylprednisolone 40 mg and clonidine 50“75 mg. The during pregnancy or immediately after labor and delivery.
patient is free to take acetaminophen and NSAIDs at home. This Symptoms, which are almost always self-limiting, can be disturb-
scheme can be repeated up to three times. If the pain is severe, the ing to the parturient and may interfere with normal daily activ-
use of a strong analgesic such as tramadol can be used as first ities. The mother should be reassured that the symptoms usually
choice in combination with acetaminophen. Acetaminophen resolve following delivery. Conservative therapy such as minimiz-
plus codeine is another option, leaving morphine as the last ing periods of standing, eliminating tight clothing, and using oral
choice (Lavand™ homme, personal communication, 2005). analgesics may contribute to recovery. As a last resort, surgical
therapy is effective in some cases.93
Most of the time, the pain has a neuropathic component. If
local infiltration is not successful, adjuvants can be added, such
as antidepressants or anticonvulsants: the latter being more
Radiological examinations during pregnancy
effective if the patient complains of a sensation of electric
and the puerperium
shocks. The antihyperalgesic effect of amitriptyline is obtained
at a lower dose than the antidepressant effect,88 so a dose of 25 mg Avoiding invasive procedures during pregnancy is one of the
(up to a maximum of 75 mg) at night is effective in this regard. dictums that is still valid. Some radiological procedures are con-

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