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OVERVIEW:
1
Edward Lichten MD, FACS
Senior Attending
2
Tengbin Xiong MCh
Research
Associate
2
George Harrison FRCOG
Consultant of
Obstetrics and Gynecology
3 Cara Glavin, MS
2
Jane Daniels
Senior Research
Fellow
2
Khalid S Khan FRCOG
Professor and
Consultant of Obstetrics and Gynecology
4
Neil P Johnson MD
Consultant of
Obstetrics and Gynecology
1 Hutzel
Hospital, 540 Henrietta Street, Birmingham, Michigan 48009, USA
2
Birmingham Women's Hospital, Metchley Park Road, Birmingham B15 2TG, UK
3
Wayne State University, College of Medicine,
Detroit, Michigan 48201 USA
4
University of Auckland and
Fertility Plus, Auckland, New Zealand
Abstract
This case study demonstrates cervical and uterine pressure in women with
primary dysmenorrhoea. It suggests that uterine nerve ablation might work
through an efferent motor nerve pathway, minimizing cervical and uterine
contraction, rather than a sensory neuro-ablation.
Introduction
Neuro-ablation treatment for
dysmenorrhoea and chronic pelvic pain (CPP) has a long history. Ruggi
[1]
in 1898 performed a sympathectomy on 12 women, successfully curing their
pain. Cotte[2]
in 1929 popularized the presacral neurectomy, which was the mainstay of
treatment until Doyle[3]
in 1955 described similar results with vaginal transection of the
utero-sacral nerves. Lichten[4]
in 1987 described the laparoscopic uterine nerve ablation (LUNA) and Perez
[5]
in 1990 described the laparoscopic presacral neurectomy (LPSN). In each
case, non-randomized studies suggested that neuro-ablation was successful in
approximately 70- 80 percent of patients at follow up. Pain outcomes are
susceptible to placebo effect, thus it is important to randomise and blind
the assessment of pain outcomes to eliminate bias. Both LUNA and LSPN
continue to be used by gynecologic surgeons today, although both have now
been exposed to the scrutiny of randomized controlled trials (RCTs).
A comprehensive systematic
review of randomized trials evidence on the efficacy of LUNA in the
treatment of chronic pelvic pain was updated in 2005
[4;7].
LPSN versus LUNA for primary dysmenorrhoea showed no significant difference
in pain relief up to 6 months; however, LPSN was shown to be significantly
more effective than LUNA up to 12 months [8].
There was no evidence of benefit of adding LUNA to the standard laparoscopic
surgical removal of endometriosis from three RCTs (n = 266) [7;9;10],
and no evidence of benefit of adding LUNA to bipolar coagulation of uterine
vessels in women with fibroids and dysmenorrhoea in one RCT (n = 80)
[11].
There is limited evidence to suggest a benefit of adding presacral
neurectomy to laparoscopic removal of endometriosis in reducing midline pain
from three RCTs (n = 205)[12-14].
There is an ongoing trial of LUNA, which is due to be reported soon
[15].
The sensory (afferent) nerve
supply to the uterus has been previously described
[16].
The motor (efferent) supply to the uterus is very complex because of
endocrine interaction, but parasympathetic activity is thought to inhibit
contractions, whereas sympathetic activity stimulates contractions[17].
The efferent preganglionic sympathetic fibres are from the last thoracic and
first lumbar spinal segments. Preganglionic parasympathetic fibres arise in
the second to fourth sacral spinal segments and relay in the paracervical
ganglia[17].
From the origin of the uterosacral ligaments on the pelvic sidewall to their
insertion into the uterus, the total nerve content decreases and the
relative composition of nerve types becomes more consistent
[18].
Overall the utero-sacral ligaments have a higher proportion of sympathetic
compared to parasympathetic fibers
[18].
There is a question to be asked
as to how LUNA might work. The primary author (EML) has had marked anecdotal
success in the context of severe primary dysmenorrhoea refractory to all
standard treatments. This clinical experience suggested that a good
therapeutic response to a paracervical block administered in the acute
stages of dysmenorrhoea might be a useful predictor of effectiveness for
LUNA.
There is evidence from uterine
pressure studies of elevated uterine pressures in women with
dysmenorrhoea[19-22].
EML designed a study to explore the possible role of cervical and uterine
contraction in primary dysmenorrhoea. We explore the observations made in
this study to delineate a hypothesis concerning a possible mechanism of
action of LUNA.
Methods
A
nulliparous woman with dysmenorrhoea during menstruation, who was known not
to have secondary causes of dysmenorrhoea or laparoscopic findings consented
to the study investigation. Two Swan-Ganz catheters were aligned with
sterile hemorrhoid bands. One catheter was aligned 1.5cm longer than the
other (figure 1). The hemorrhoid bands were placed at 1.5cm below the
shorter catheter. Therefore, when the bands were at the cervical os, the
shorter catheter was in the cervix and the longer catheter was in the
uterine cavity. Using a dual pressure recording system, the uterine
pressure tracings were recorded on the first day of menstruation.
Results
The recorded baseline pressures
and amplitude spikes appear in figure 2. High baseline pressure was recorded
in both the uterus and cervix.
The amplitude of uterine contractions exceeded 250 mm Hg. The pressure in
the cervix showed frequent spikes to 50 mm Hg. After recording the tracing
for more than 30 minutes, a paracervical block was performed, injecting 5ml
of 1% lidocaine into the cervix at 4 and 8 o’clock position. Within 30
seconds, the pressure tracing in the cervix changed. The amplitude dropped
and the frequency of cervical contractions became less
frequent
identified in figure 3. In addition, the change in pressure in the uterus
reverted to a lower amplitude with a low baseline. The changes in
the uterus followed the normalization of pressure in the cervix. The patient
reported clinical relief of pain at the same time as the change in uterine
pressures.
Discussion
What this study has showed
It
seems likely that dysmenorrhoea in this individual was associated with
increased baseline pressure and amplitude spikes from uterine contractions,
not unlike those observed during labor and delivery. It is also possible
that increased cervical pressure caused a physiological obstruction to the
normal menstrual flow through the cervix. The result of the paracervical
block was a drop in cervical baseline pressure and contraction frequency.
Subsequently, the uterine contraction amplitude, baseline pressure and
frequency began to decrease until reaching a normal pattern.
Strengths and weakness of this study
Swan Ganz catheters are constructed with pressure sensors in the tips and
avoid the distortion and effects of the longstanding balloon technology used
by previous authors [21-24].
However, Swan Ganz catheters are intravascular measuring devices, and have
been designed for that purpose. The use of them within a potentially empty
cavity such as the uterus is less clear, and the result may depend upon the
orientation of the catheter.
How the results agree/disagree with previous studies
Other studies have also
suggested that elevated pressure in cervix prevents flow of blood through
the cervical os, acting as a possible ‘contraction ring’[25].
Lipiodol injections into the uterus also seemed to support the concept of a
sphincter activity of the uterine isthmus[26;27].
Physiological correlations
Elastic connective tissue
fibers are present in the cervix parallel to the endocervical canal[28].
The muscle fibers in the inner part of the cervix are similarly oriented,
although the outer ones are orientated circumferentially. Could the muscle
fibers oriented parallel to the cervical isthmus generate a low pressure
over the length of the canal to obstruct menstrual flow? The primary author
(EML) created an anatomical model of the cervix based on the standard
measurements [29].
The conditions for the cervical model were the following: (a) firm, exterior
surface of the cervix that was relatively inflexible; (b) orientation of
muscle fibers parallel to cervical isthmus interspersed with elastic fibers;
(c) internal cervical os measurements: internal cervical os (isthmus) 5mm;
(d) maximal muscle contraction under normal physiological conditions is
approximately 22%[30].
Under these conditions, it was observed that contraction of muscle fibers in
the longitudinal axis has the potential to narrow the internal os by 4.5
mm. The shortening of the longitudinal fibers results in a “fattening” in
its mid-portion which “bulges” into the cervical isthmus. This model adds
support to the obstructive hypothesis of primary dysmenorrhoea. Just as in
the urethra, low pressure over an extended distance can prevent flow of
fluid. This narrowing at the internal os and isthmus, where the maximum
concentration of cervical muscle fibers are found, further explains why the
pressures we recorded in the cervix were less than one-quarter of the
pressure measured simultaneously within the uterus.
There is evidence to suggest
that the passive biomechanical strength of the cervix markedly exceeds the
active muscular contractile ability. This may be explained by a high
collagen concentration and a low content of smooth muscle in the cervical
tissue[31].
This questions the possibility of the cervix contracting to the extent that
it causes a bulging of the cervical wall, and questions the validity of the
anatomical model described above. Also, if this did occur in patients with
dysmenorrhoea, the question has to be answered as to why it does not occur
in women without dysmenorrhoea.
If LUNA is indeed effective for
primary dysmenorrhoea, it could be ablating motor efferent nerve fibers that
supply these ‘circular, sphincter-like’ cervical muscles and also the
myometrium. This might be an alternative explanation to the ablation of
sensory afferent uterine nerves in the LUNA procedure. Likewise, any
surgical procedure that interrupted the motor nerves to these muscles, or
dilated or over-stretched the cervix, might also prevent the cervical
sphincter from obstructing menstrual flow. The reduction in intra-uterine
pressure and intra-cervical pressure in this study was seen within 30
seconds of the lidocaine injection, a surprisingly rapid response. It is
debatable whether a motor block can be produced without a sensory block, as
in vivo studies have indicated that sympathetic fibres (which would usually
be the motor fibres) tend to be blocked more slowly than small sensory
fibres[32].
However the excess of sympathetic fibres in the uterosacral ligament might
be sufficient to produce a selective motor block[18].
Conclusion
The
laparoscopic uterine nerve ablation might relieve the pain of primary
dysmenorrhoea through an efferent motor nerve pathway by minimizing cervical
and uterine contraction, rather than due to the sensory neuro-ablation.
Further research is required to confirm this mechanism by comparison studies
involving a larger number of women.
Picture 1:
Dual Swan-Ganz catheters of unequal length. The longer is placed in
the uterus, the shorter one, in the cervical isthmus. The upper band
is placed at the external cervical os.
Figure 1:
Uterine tracings shown
above, cervical tracings below from Swan-Ganz pressure catheters.
Tracings recorded at 5mm/min. Y-axis recorded pressure in mm Hg.
Figure 2: Same
patient. Ten minutes after paracervical block with 10cc of 1%
lidocaine. X-axis is recorded at 25mm/ minute to allow for closer
scrutiny of uterine and cervical contraction patterns. Note the
absence of the uterine pressure spikes, the maximum pressure of just
over 100mg Hg and the decrease in uterine baseline pressure. The
lower graph shows the independent cervical contraction pattern with
maximum contraction amplitude of 30 mm Hg over baseline pressure.
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