Effectiveness of laparoscopic uterine nerve ablation (L.U.N.A.) for primary dysmenorrhoea-- might be due to efferent motor nerve ablation rather than sensory neuroablation

Edward Lichten, M.D.,PC
555 South Old Woodward Suite #700
Birmingham, MI 48009 
248.593.9999

Email: drlichten@yahoo.com
 

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.