Abstract
Introduction
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Several theories for PV etiology have been proposed. As recently as 2013, the types of vaginal lactobacilli and cytokines in patients with PV, compared to matched healthy controls, were quantified. A preliminary report concluded that a vaginal flora alteration and an immunologic response involving Candida were present in patients with PV. 1
In the past, vaginal birth trauma was considered a predisposing factor for vulvar pain. However, an article published in 2012 regarding primigravidas without episiotomy noted that, while 25% of patients had vaginal lacerations, <10% of patients complained of vulvar pain at their postpartum visits. 2
Neuropathic Pain
Neuropathic pain (NP) is the most prominent feature of PV and is the most distressing feature for patients. Moreover, PV is the most common form of chronic dyspareunia. NP occurs from injuries or diseases affecting the somatosensory component of the nervous system at any level of the peripheral nervous system or the central nervous system (CNS). 3
The pathophysiologic bases of—and management approaches for—nociceptive pain are entirely different from those involved with NP. However, the bases of nociceptive pain may still share with NP the quality of being less somatic and more affective in nature when the pain becomes chronic. 4 Therefore, any intervention that could be used to relieve pain is, as a rule, appreciated by patients.
Our understanding of the sensory nervous system has increased exponentially as has our knowledge of pain and its inherent neuromodulation.5,6 In addition, the anatomical and pathophysiologic aspects of vulvar pain were described in 2013. 7
Today, clinical use of neuropharmacologic mediators to address pain make evident that targeted psychotropic interventions could be useful for managing difficult PV cases. For instance, modulation of pain circuitry by neuromodulators from the peripheral nervous system to the CNS should be strongly considered.
Analgesia is one of the principal therapeutic targets of cannabinoids. However, the indiscriminate use of cannabinoids may lead to abuse and overdoses, with their related unintentional consequences.3,8 Invasive therapies include spinal and intrathecal injections, nerve blocks, and ablations, and nerve stimulation maybe be also less indicated for PV. 9 There is an increased incidence of chronic pain worldwide as well as in the United States, and pain therapy has progressed to address the increasing need for medical relief options. Therefore, a targeted stepwise protocol that is devoid of narcotics and less invasive should be considered for treating PV that is unresponsive to other therapies.
Pain Neuromodulation
The concept of pain neuromodulation was introduced in literature in the 1980s.5,6,10 The underlying principle is based on anatomical and physiologic considerations. Skin receptors receive nociceptive stimuli and fibers transport them to the CNS. Such information undergoes considerable blending, amplification, and/or reduction that affect the physical and emotional responses to the original stimuli. These modifications might occur at any point of the afferent pathway and could be used as targets for pain intervention. 5
Therefore, it should be possible to intervene in pain transmission and perception with neuromodulators. Neuromodulators (e.g., tricyclic antidepressants, gabapentin, and pregabalin), neurotransmitters, β-endorphins, encephalins, and serotonin have become important for pain modulation through complex inhibitory and excitatory pathways, as predicted by Ignelzi and Atkinson in 1980. 6
Pain Modulation in PV
A Medline® search conducted on December 21, 2015, regarding precisely
We utilized small doses of the medications, and when any patient did not improve by 30–45 days, we added a second and/or third medication. The medications were recommended for 3–6 months of use, and patients were weaned off based on their symptomatic relief. The doses were as follows: 25–50 mg of amitriptyline; 100–200 mg of gabapentin; and 37.5 mg of venlafaxine. 11 The cohort recently completed a 5-year follow-up. Recurrences were only at 7.5%.
Treatment Rationale
NP is diagnosed based on neurologic signs and symptoms. The first complete therapeutic guidelines were available more than 10 years ago. Those guidelines suggested using tricyclic antidepressants, anticonvulsants, and opioids. 12 Much more-recent treatment protocols for chronic neuropathic pain include a combination of multiple approaches and modalities: conservative; complementary; pharmaceutical; interventional; and surgical. 13
Current pharmaceutical guidelines recommend using amitriptyline, duloxetine, gabapentin, and pregabalin. Pregabalin is the only drug recommended for first-line therapy. Opioids are in the second or third line. 14 In addition, observations in 2014 by Mansur et al. demonstrated that we should consider redefining chronic pain based on brain plasticity and remodeling, within the associative learning and valuation concept. 4 This is because, according to the researchers' theory, in chronic pain conditions such as PV, the brain develops an inability to switch off the emotional memory and the motivational mesolimbic–prefrontal brain circuit memory. These researchers imply that supraspinal/cortical manipulations may be necessary for an adequate modulation of the suffering and related behavior that patients with chronic pain manifest. 4 In addition to this, mindfulness-based cognitive behavioral therapy should also be considered. 15
Therefore, addressing pain with neuromodulators of the peripheral nervous system (such as tricyclic antidepressants) and the CNS (such as anticonvulsants and serotonin–norepinephrine reuptake inhibitors) seems to be physiologically sound.
Conclusions
The best treatment for PV is still under investigation. However, should a pain neuromodulation therapeutic approach for PV implemented in a stepwise manner be taken in consideration?