Intra-vaginal Electrical Stimulation Device Compared to Sham Device for Chronic Pelvic Pain

Chronic pelvic pain (CPP) is a complex and devastating diagnosis, encompassing multiple
different conditions. Many organ systems may be involved including musculoskeletal,
neurologic, genitourinary, psychiatric or gastrointestinal systems. Furthermore, it can be
associated with major insomnia, psychosexual trauma, and mood disorders resulting in
challenging cases characterized by pain that is refractory to standard treatment modalities.
In a study conducted by Mathias et al., one in seven women experience chronic pelvic pain.
The economic burden can be substantial, with previous estimates of 2.8 billion dollars per
year. (1) Dyspareunia is defined as recurrent or persistent pain associated with sexual
intercourse and affects approximately 8-21% of women in the United States (19, 20).
Understandably, women with dyspareunia often suffer a decline in sexual functioning. It may
lead to decreased arousal, loss of libido, and anorgasmia. However, its impact extends beyond
sexual functioning as it can affect a woman's reproductive health and overall sense of
well-being. Previous estimates indicate that 88% of sexually active chronic pelvic pain
patients report pain during or after intercourse (1).

Treatment of chronic pelvic is challenging due to a poor understanding of pain processing and
physiology. Each patient's experience of pain is unique and may be any combination of
visceral, neuropathic, or even somatic in etiology. Persistent pain despite aggressive
treatment of organic etiologies may imply a psychogenic overlay. A comprehensive and
integrative approach is ideal and may include physical therapy, medications, or cognitive
behavioral therapy.

Pelvic floor physical therapy is an effective treatment. Pelvic floor rehabilitation
addresses the pelvic floor dysfunction and may include manual therapy, transvaginal
biofeedback and electrical stimulation. Reissing et al. performed a retrospective chart
review and discovered that physical therapy, particularly internal manual techniques, is a
successful technique in treating patients with vaginismus (5). Electrical stimulation (ES) to
the pelvic floor is an effective treatment in vaginismus, vulvar vestibulitis, urinary
urgency, and levator ani hypertonus (11-15). ES delivered specifically through a
transcutaneous electrical nerve stimulator (TENS) unit results in notable benefit in pain and
dyspareunia (8,12,21-23). Murina et al. conducted a randomized controlled trial comparing use
of a vaginal probe delivering electrical stimulation to a sham device. In this study, they
used a TENS unit to treat vestibulodynia using a protocol of 15 min of 10 Hz followed by 15
minutes of 50 Hz. These sessions were completed on a twice per week basis for 10 weeks. Pain
scores, dyspareunia and overall sexual functioning were significantly improved in the active
arm compared to placebo (8). Another study used a TENS unit to treat primary dysmenorrhea. In
this protocol, the TENS unit was set to 100 Hz with 100ms pulse width for the first 8 hours
of the menstrual cycle and then repeated for another menstrual cycle (9). A smaller study of
12 women used electrical stimulation biofeedback and gradual desensitization in the treatment
of vaginismus. After treatment, all 12 women were able to have vaginal intercourse (13).

Electrical stimulation is used extensively for the treatment of various pain disorders. It is
delivered through peripheral nerve stimulation, a TENS unit, or sacral neuromodulation using
an implantable device. Electrical stimulation has three different programmable settings
including the frequency, intensity and pulse duration. High frequency is considered as > 50
Hz whereas low frequency is < 10 Hz. The intensity, also known as the power, of the unit can
be set to a sensory or motor threshold with any frequency (2).

There are several theories to explain the mechanism of action of electrical stimulation. TENS
works by altering the ability to perceive pain signals. The gate theory is one proposed
mechanism of action. Electrical stimulation of nerves via a specific dermatome results in a
blocking or gating effect at the dorsal horn of the spinal cord. This inhibits the
transmission of pain impulses to the upper nervous system. Also, low frequency stimulation of
the dermatome can increase the level of endorphins, providing pain relief. (2) The sacral
nerve roots 2-4 hold the autonomic and somatic innervation of the pelvic floor, bladder, and
urethra. Therefore, stimulation of the sacral nerve roots 2-4 can provide a means to modulate
impulses from the pelvic floor. Inhibition of afferent innervation from the pelvic floor or
bladder is achieved with afferent activation of the sacral nerve roots using Interstim® or
similar devices. In other words, stimulating the sacral nerve roots through neuromodulation
has an inhibitory effect on pain pathways at the spinal cord level. (3) Treatment of chronic
pelvic pain may include peripheral nerve stimulation via the posterior tibial nerve. This
mixed nerve shares the same spinal origin as the innervation of the bladder and pelvic floor.
Stimulation of the posterior tibial nerve travels retrograde to modulate the afferent input
from the bladder or pelvic floor. (4) Therefore, it shares a similar mechanism of action to
sacral neuromodulation but spares the patient the complications associated with surgical
implantation of a device.

Despite its efficacy and benefits, electrical stimulation is time intensive and dependent
upon a health care provider's schedule. It often causes the patient social embarrassment
resulting in its inaccessibility. Although electrical stimulation provides pain relief, even
highly motivated patients report that anxiety prohibits them from participation in
physiotherapy (6). The investigators propose a novel treatment using a non-implanted
intra-vaginal electrical stimulation device to be used in the comfort and privacy of the
patient's home. This addresses several barriers associated with in office, standard pelvic
floor physical therapy. Furthermore, a personal device allows the patient a more active role
in her treatment, which can be empowering and ultimately, therapeutic.

InControl Medical created a line of products FDA approved for urinary incontinence and fecal
incontinence (10). These devices are non-implanted, customizable, battery-operated vaginal
probes made of medical grade silicon and provide electrical stimulation to the pelvic floor.
One of the devices, ApexM™ provides electrical stimulation at frequencies alternating between
13 Hz and 50 Hz and allows the clinician to adjust the intensity as well as the duration of
the electrical stimulation. The investigators propose the use of low power electrical
stimulation for the treatment of pain in patients diagnosed with CPP. The electrical
stimulation is delivered using ApexM™, adjusting the power to a sensory threshold to prevent
muscle contraction.

The goal of the study is to evaluate the use of a personal intravaginal, non- implanted
electrical stimulation device in the treatment of chronic pelvic pain. The investigators
propose a randomized controlled trial comparing the investigated device to a sham device. The
primary outcome is pain control using the visual analog scale and brief pain inventory (18).
Hypothesis: Subjects will report increased pain relief with the electrical stimulation device
compared to those using the sham device alone.

Secondary goals:

To evaluate the effect of ES on overall quality of life. Hypothesis: ES will improve quality
of life as measured by the Short Form-36. (16) To evaluate the effect of ES on sexual
function. Hypothesis: ES will improve sexual functioning as measured by Female Sexual
Function Index (17) To evaluate the use of ES on use of pain medications. Hypothesis: ES will
decrease dosage and frequency of pain medication use. This will be measured by use of a daily
pain medication journal. Patients will complete a journal listing the type, amount and dosage
of pain medications used on a daily basis.

SIGNIFICANCE If a positive effect is seen, a personal vaginal device designed for home use
can be offered to patients with chronic pelvic pain. Patients would be able to take pelvic
floor rehabilitation from the physical therapy office into their home. Furthermore, it would
justify a larger, multi-center, randomized controlled trial comparing the ApexM™ device to
standard in office physical therapy.

Inclusion Criteria:

- Women >/= 18 years old who are sexually active or desire to be sexually active, no
active infection, diagnosed with non-cyclic chronic pelvic pain, duration of symptoms
greater than 6 months, neurologically intact, able to accommodate and tolerate the
device, not pregnant and not attempting to achieve pregnancy.

Exclusion Criteria:

- Pregnancy, currently active in pelvic floor physical therapy, active malignancy,
patients unable to contract their pelvic floor secondary to causes such as myelopathy,
spinal cord trauma, patients with diabetes, vestibulodynia, vulvodynia, a pacemaker,
defibrillator or other implanted neuro-modulatory devices, patients with a hypotonic
pelvic floor, or those currently on treatment for pain with topical lidocaine,
gabapentin or other medications or injections outside of standard analgesics, and
severe psychiatric disorders