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With great excitement, we read the comprehensive review published by Hao et al. in Pain and Therapy [1]. This is an important review of rehabilitation strategies for patients with chronic pelvic pain, a condition often neglected in terms of applied clinical research. In the narrative review, the authors addressed several neuromodulation techniques, such as sacral neuromodulation, conus medullaris stimulation, dorsal root ganglion stimulation, dorsal column spinal cord stimulation, and pudendal nerve stimulation [1]. The evidence points to clinical benefits for all the modalities mentioned but with concern about studies that have limited methodological quality and heterogeneity. Hao et al. criticized this situation, calling for attention to the lack of randomized controlled studies for neuromodulatory treatments [1].
Although the authors focused on non-brain searches for peripheral neuromodulation treatments, it is suggested that chronic pelvic pain leads to maladaptive neuroplasticity and functional reorganization in brain areas related to pain perception [2]. Chronic pelvic pain also causes dynamic changes in the functional pain connectome, as previously shown for women with primary dysmenorrhea [2]. This process interferes with the affective processing and cognitive modulation of pain [2]. It is important to note that the primary somatosensory and primary motor cortex are related to the processing of pain. These cortical sites are interconnected and involved in pain modulation [3, 4]. Considering these assumptions, central sensitization should be the focus of research related to chronic pelvic pain. Neuromodulation therapies that directly interfere with brain functioning deserve attention, a fact that we feel is lacking in Hao et al.'s review. One of the neuromodulation techniques suggested to treat chronic pelvic pain is transcranial direct current stimulation (tDCS) [5, 6]. tDCS is a non-invasive, safe, low-cost neuromodulation technique with minimal adverse effects [7]. According to the montage, tDCS has the potential to change sensory excitability and pain thresholds [8]. Anodal tDCS over the primary motor cortex or the dorsolateral prefrontal area has been performed in randomized clinical trials aimed at improving pain in women with pelvic dysfunction [9, 10]. Despite some data showing that tDCS generates promising results for improving pain symptoms, the physiology involved is still under investigation. In a preliminary study using tDCS for the treatment of refractory chronic pelvic pain, Fenton et al. suggested a prolonged effect of the active treatment compared to the sham group, showing a 14% difference between them for pain symptoms [6]. Recently, two randomized controlled trials of tDCS in women with primary dysmenorrhea showed promising data for the improvement of pain and behavioral aspects, such as anxiety [9, 10]. In addition, one of the studies showed an improvement in the functional capacity of the participants [10]. The effects of tDCS on pain and mood disorders appear to be dependent on the electrode assembly to modulate brain areas related to pain control [7].
In a Cochrane review of 747 patients presenting chronic pain, tDCS compared with sham reduced pain intensity by 17% [11]. tDCS can generate long-term effects increasing or inhibiting the cortical areas. The excitability alteration is modulated by N-methyl-D-aspartate expression and γ-aminobutyric acid (GABA) release. Glutamate and GABA are neurotransmitters associated with excitatory and inhibitory pathways [12]. Recent research also showed that tDCS alters voltage-gated potassium channels, amplifying axonal depolarization and repolarization [13]. In fact, synaptic plasticity and functional modifications play an important role in neuroplasticity and central pain modulation [7]. As discussed, chronic pain experienced by people is complex because of the involvement of different mechanisms and structures. So, it is coherent to affirm that people affected by chronic pelvic pain may present central nervous system dysfunctions.
Non-invasive and safe treatments focused on brain regions that process pain signals must be encouraged. tDCS appears to be a promising tool with good preliminary results in patients with chronic pelvic pain, impacting not only the painful symptom but also behavior and function [9, 10]. tDCS has huge potential for use in populations related to women's health and can be performed in home-based rehabilitation and remotely adjusted. New clinical trials on this topic are ongoing, and promising prospects indicate the routine use of tDCS for chronic pelvic pain.
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Acknowledgements
Funding
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.
Author Contributions
Rodrigo Pegado: concept and drafting the manuscript; Edson Meneses Silva-Filho: concept and drafting the manuscript; Maria Thereza Albuquerque Barbosa Cabral Micussi: drafting the manuscript and proofreading.
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Rodrigo Pegado, Edson Meneses Silva-Filho and Maria Thereza Albuquerque Barbosa Cabral Micussi have nothing to disclose.
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This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
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Pegado, R., Silva-Filho, E. & Micussi, M.T.A.B.C. Letter to the Editor Regarding ‘Neuromodulation for Management of Chronic Pelvic Pain: A Comprehensive Review’. Pain Ther 12, 1095–1097 (2023). https://doi.org/10.1007/s40122-023-00517-x
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DOI: https://doi.org/10.1007/s40122-023-00517-x