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Parameters and results of non-invasive neuromodulation in the management of chronic pelvic pain: integrative literature review

ABSTRACT

BACKGROUND AND OBJECTIVES:

Chronic Pelvic Pain (CPP) is characterized by persistent pain in the pelvic region for more than six months, affecting both men and women and causing significant impairment in quality of life (QoL). Two of the main non-invasive approaches are Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). These techniques aim to modulate neural activity and promote pain relief. In this context, this research conducted an integrative literature review to summarize the results of relevant studies, aiming to identify the key parameters used in TMS and tDCS for CPP treatment. The objective was to assess the effect and efficacy of non-invasive neuromodulation as a therapeutic intervention for CPP.

CONTENTS:

For this integrative review, electronic searches were conducted in Pubmed, Scielo, PEDro, Medline, Cochrane, and Scopus databases, examining studies in Portuguese, English, or Spanish. The keywords “pelvic pain,” “transcranial direct current stimulation,” and “transcranial magnetic stimulation” and their derivatives were searched in the three languages in studies from 2013 to 2023. Seven studies were included for analysis. Both techniques showed positive effects in managing CPP, improving pain levels and quality of life to a relevant extent. However, there is still no consensus on the parameters applied in TMS and tDCS techniques for CPP.

CONCLUSION:

Non-invasive neuromodulation improves pain levels and quality of life in patients with CPP. Further studies are needed to establish more reliable parameter relationships, and the limited number of studies restricts definitive conclusions on the subject.

Keywords
Chronic pain; Non-invasive neuromodulation; Pelvic pain; Transcranial magnetic stimulation; Transcranial direct current stimulation

RESUMO

JUSTIFICATIVA E OBJETIVOS:

A dor pélvica crônica (DPC) é caracterizada pela persistência da dor na região pélvica por mais de seis meses, afetando tanto homens quanto mulheres e causando prejuízos significativos na qualidade de vida (QV). Duas das principais abordagens não invasivas são Estimulação Magnética Transcraniana (EMT) e a Estimulação Transcraniana por Corrente Contínua (ETCC). Nesse contexto, esta pesquisa realizou uma revisão integrativa da literatura com o intuito de resumir os resultados de estudos relevantes, buscando identificar os principais parâmetros utilizados no tratamento da DPC. O objetivo foi fornecer uma visão abrangente sobre essas técnicas de neuromodulação e suas aplicações específicas no controle da dor pélvica crônica.

CONTEÚDO:

Para esta revisão integrativa, as buscas eletrônicas ocorreram nas bases de dados Pubmed, Scielo, PEDro, Medline, Cochrane e Scopus, verificando estudos em português, inglês ou espanhol. “Dor pélvica”, “estimulação transcraniana por corrente contínua” e “estimulação magnética transcraniana” e suas derivações foram pesquisadas nos três idiomas em estudos entre 2013 e 2023. Sete estudos foram incluídos para análise. Ambas as técnicas apresentaram efeitos positivos no manejo da DPC, melhorando os níveis de dor e a QV em proporções relevantes. Entretanto, ainda não há um consenso sobre os parâmetros aplicados nas técnicas de EMT e ETCC para DPC.

CONCLUSÃO:

A neuromodulação não invasiva melhora os níveis de dor e a QV em pacientes com DPC. São necessários mais estudos para que relações mais confiáveis de parâmetros possam ser preestabelecidas e a ausência de um maior número de estudos limita conclusões acerca do assunto.

Descritores
Dor crônica; Dor pélvica; Estimulaçao magnética transcraniana; Estimulaçao transcraniana por corrente contínua; Neuromodulaçao não invasiva

HIGHLIGHTS

  • There is a need for standardization and consensus on the parameters of neuromodulation techniques for chronic pelvic pain.

  • The stimulation area includes the motor cortex and the dorsolateral prefrontal cortex.

  • Neuromodulation techniques, such as Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation, have shown potential in addressing not only pain but also other aspects such as sleep, cognitive complaints, fatigue, catastrophizing, depression, and mood in patients with chronic pelvic pain.

HIGHLIGHTS

  • There is a need for standardization and consensus on the parameters of neuromodulation techniques for chronic pelvic pain.

  • The stimulation area includes the motor cortex and the dorsolateral prefrontal cortex.

  • Neuromodulation techniques, such as Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation, have shown potential in addressing not only pain but also other aspects such as sleep, cognitive complaints, fatigue, catastrophizing, depression, and mood in patients with chronic pelvic pain.

INTRODUCTION

Chronic pelvic pain (CPP) is pain in the pelvic area persisting for at least six months, affecting both genders and diminishing overall well-being, daily functionality, and emotional health. It may also induce symptoms of anxiety and depression11 Divandari N, Manshadi FD, Shokouhi N, Vakili M, Jaberzadeh S. Effect of one session of tDCS on the severity of pain in women with chronic pelvic pain. J Bodyw Mov Ther. 2019;23(3):678-82.. Approximately 4% to 16% of women have CPP, with a third requiring medical aid due to severe symptoms22 Calabrò RS, Billeri L, Porcari B, Pignolo L, Naro A. When two is better than one: a pilot study on transcranial magnetic stimulation plus muscle vibration in treating chronic pelvic pain in women. Brain Sci. 2022;12(3):396.. The prevalence of CPP surpasses that of ailments like asthma or migraines, presenting significant public health concerns33 Nogueira AA, Reis FJC, Poli Neto OB. Abordagem da dor pélvica crônica em mulheres. Rev Bras Ginecol Obstet. 2006;28(12):733-40..

The pathophysiology of CPP is intricate, often tied to multiple disorders including neurological, neuroendocrine, and stress disorders. Several pelvic pain conditions can coexist, with symptom overlap attributed to mechanisms such as viscero-visceral cross-sensitization, where activity in one organ may hypersensitize another. This long-term exposure to pain stimuli can lead to central sensitization, an altered central nervous system (CNS) pain perception due to neuroplasticity44 Lamvu G, Carrillo J, Ouyang C, Rapkin A. Chronic pelvic pain in women: a review. JAMA, 2021;325(23):2381-91.,55 Stratton P, Khachikyan I, Sinaii N, Ortiz R, Shah J. Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain. Obstet Gynecol. 2015;125(3):719-28..

CPP’s multifactorial nature includes gynecological, urological, gastrointestinal, and psychological dimensions66 Engeler D. Guidelines on chronic pelvic pain. Eur Assoc Urol. 2022.. A comprehensive approach is vital, yet about 60% of affected women never receive a definitive diagnosis33 Nogueira AA, Reis FJC, Poli Neto OB. Abordagem da dor pélvica crônica em mulheres. Rev Bras Ginecol Obstet. 2006;28(12):733-40.. Current CPP treatment prioritizes symptom management. Non-invasive neuromodulation, part of the expanding field of neuromodulation, emerges as a promising therapeutic avenue77 Shi JY, Paredes Mogica JA, De EJB. Non-surgical management of chronic pelvic pain in females. Curr Urol Rep. 2022;23(10):245-54..

According to the International Neuromodulation Society (INS), neuromodulation acts directly on the Central Nervous System (CNS), generating an alteration or modulation of neural activity through the distribution of electrical or pharmacological agents in a specific area. Among the types of neuromodulation, noninvasive brain stimulation (NIBS) techniques are considered promising therapies88 Zheng Y, Mao YR, Yuan TF, Xu DS, Cheng LM. Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation. Neural Regen Res. 2020;15(8):1437-50., used in the treatment of various pain conditions, such as neuropathic, inflammatory, trigeminal and nociplastic pain99 Toledo RS, Stein DJ, Sanches PRS, da Silva LS, Medeiros HR, Fregni F, Caumo W, Torres ILS. rTMS induces analgesia and modulates neuroinflammation and neuroplasticity in neuropathic pain model rats. Brain Res. 2021;1762:147427., including chronic pelvic pain. This technique involves modulating neural activity through the application of an electrical or magnetic current to a target area1010 Kesikburun S. Non-invasive brain stimulation in rehabilitation. Turk J Phys Med Rehabil. 2022;68(1):1-8..

The main non-invasive techniques are Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS)1111 Soler MD, Kumru H, Pelayo R, Vidal J, Tormos JM, Fregni F, Navarro X, Pascual-Leone A. Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury. Brain. 2010 Sep;133(9):2565-77.. The mechanism of both techniques is not fully understood, but it is suggested that they modulate brain function, inducing neuroplasticity in the CNS by modifying the resting membrane potential and altering neuronal activity through the direct application of an electrical current or the creation of an electric field with magnetic induction on the scalp44 Lamvu G, Carrillo J, Ouyang C, Rapkin A. Chronic pelvic pain in women: a review. JAMA, 2021;325(23):2381-91.. TMS promotes depolarization, while tDCS alters the membrane potential. The affected sites include the prefrontal cortical network, including the dorsolateral prefrontal cortex (DLPFC), and the primary motor cortex (M1)1212 Mahoney JJ 3rd, Hanlon CA, Marshalek PJ, Rezai AR, Krinke L. Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment. J Neurol Sci. 2020;418:117149..

TMS is a safe neuromodulatory technique based on Faraday’s law of electromagnetic induction. A coil placed on the scalp generates a perpendicular magnetic field that reaches the targeted region, making it non-invasive. Due to its time-varying characteristics, it generates an electric field and electric currents at the target site1313 Somaa FA, de Graaf TA, Sack AT. Transcranial magnetic stimulation in the treatment of neurological diseases. Front Neurol. 2022;13:793253.. This tool uses an electromagnetic field to alter neuronal electrical activity and modify firing patterns, resulting in various connectivity modifications88 Zheng Y, Mao YR, Yuan TF, Xu DS, Cheng LM. Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation. Neural Regen Res. 2020;15(8):1437-50.. Furthermore, low-frequency TMS with a frequency of 1 Hz, pulse width of 1 ms, and intensity of 200 mT (millitesla) has demonstrated analgesic effects due to its inhibitory effects on the brain99 Toledo RS, Stein DJ, Sanches PRS, da Silva LS, Medeiros HR, Fregni F, Caumo W, Torres ILS. rTMS induces analgesia and modulates neuroinflammation and neuroplasticity in neuropathic pain model rats. Brain Res. 2021;1762:147427..

A guideline1414 Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipović SR, Grefkes C, Hasan A, Hummel FC, Jääskeläinen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorová I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. mentioned the promising effects of TMS in different cases of chronic pain (CP), focusing on the two main targets of TMS in the pain domain, namely M1 and DLPFC. Studies have shown that TMS has been successfully used when applied to M1 and DLPFC in cases of CP, including migraines, headaches, and low back pain. The results demonstrated a significant reduction in persistent pain intensity after applying the technique, with long-lasting effects for several weeks. Research on low back pain also showed a significant analgesic effect after a 5-day application protocol on the right M1. However, data are still scarce for other CP syndromes to recommend specific TMS parameters1515 Leung A, Metzger-Smith V, He Y, Cordero J, Ehlert B, Song D, Lin L, Shahrokh G, Tsai A, Vaninetti M, Rutledge T, Polston G, Sheu R, Lee R. Left dorsolateral prefrontal cortex rTMS in alleviating MTBI related headaches and depressive symptoms. Neuromodulation. 2018;21(4):390-401

16 Ambriz-Tututi M, Alvarado-Reynoso B, Drucker-Colín R. Analgesic effect of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic low back pain. Bioelectromagnetics. 2016;37(8):527-35.
-1717 Leung A, Shukla S, Fallah A, Song D, Lin L, Golshan S, Tsai A, Jak A, Polston G, Lee R. Repetitive transcranial magnetic stimulation in managing mild traumatic brain injury-related headaches. Neuromodulation. 2016;19(2):133-41..

The physiological effects of tDCS in pain management have been studied since the 1960s. This intervention induces changes in the neuronal membrane potential by altering extracellular ion concentrations. Therefore, tDCS is seen as a purely modulatory intervention by promoting synaptic plastic changes and positive regulation in M1, potentially and indirectly modifying pain perception through thalamic nuclei1111 Soler MD, Kumru H, Pelayo R, Vidal J, Tormos JM, Fregni F, Navarro X, Pascual-Leone A. Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury. Brain. 2010 Sep;133(9):2565-77..

In evidence-based guidelines1818 Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92., tDCS targets M1 or DLPFC in cases of CP, with most studies applying anodal stimulation to the M1 of the contralateral hemisphere (for focal or lateralized pain) or to the M1 of the dominant hemisphere (for more diffuse pain). Studies have shown that a single session of tDCS can provide significant pain relief1818 Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92..

Reliability for applying the intervention is evaluated based on factors such as safety, tolerability, cost, and, most importantly, adverse effects. tDCS, in particular, has an adverse effects rate of 10-40% among individuals undergoing neuromodulation, with the main side effects being itching, headache, burning sensation, discomfort, and tingling1919 Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P, Cohen LG, Fregni F, Herrmann CS, Kappenman ES, Knotkova H, Liebetanz D, Miniussi C, Miranda PC, Paulus W, Priori A, Reato D, Stagg C, Wenderoth N, Nitsche MA. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol. 2016;127(2):1031-48. On the other hand, TMS may induce non-severe symptoms such as headache, discomfort, and pain at the stimulation site. All reported symptoms are mild and transient2020 Wang WL, Wang SY, Hung HY, Chen MH, Juan CH, Li CT. Safety of transcranial magnetic stimulation in unipolar depression: A systematic review and meta-analysis of randomized-controlled trials. J Affect Disord. 2022;301:400-25.

The parameters used are one of the factors directly influencing the therapeutic effect of NIBS. In TMS, these measures can be exemplified and modulated based on the type of magnetic field, amplitude, coil type, frequency, and number of sessions. The parameters used play a significant role in influencing the therapeutic effects of NIBS. In the case of repetitive Transcranial Magnetic Stimulation (rTMS), these measures include the type of magnetic field, amplitude, coil type, frequency, and number of sessions2121 Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, Jreige Iskandar A, Guerrero C, Amescua-García C, Kraychete DC, Caparelli-Daquer E, Atencio E, Piedimonte F, Colimon F, Hazime FA, Garcia JBS, Hernández-Castro JJ, Cantisani JAF, Karina do Monte-Silva K, Lemos Correia LC, Gallegos MS, Marcolin MA, Ricco MA, Cook MB, Bonilla P, Schestatsky P, Galhardoni R, Silva V, Delgado Barrera W, Caumo W, Bouhassira D, Chipchase LS, Lefaucheur JP, Teixeira MJ, de Andrade DC. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019 Jan 9;4(1):e692.. Previous studies have shown that different rTMS protocols can either increase or suppress neural activity, as well as affect the duration of stimulation effects88 Zheng Y, Mao YR, Yuan TF, Xu DS, Cheng LM. Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation. Neural Regen Res. 2020;15(8):1437-50.. Conversely, in tDCS, parameters such as amplitude, duration, electrode size, and number of sessions are considered.

Despite the increasing number of publications addressing the role of NIBS in the management of CPP, a notable variability persists in both outcomes and methodological approaches across studies. This inconsistency underscores the imperative for a review and synthesis of the existing literature. Consequently, the primary aim of the present study was to assess the effect and efficacy of non-invasive neuromodulation as a therapeutic intervention for CPP.

CONTENTS

This study is an integrative literature review with the purpose of summarizing the results of a set of research studies on a specific topic. This approach aims to link research evidence with healthcare practices, with the potential to contribute for healthcare assistance. To organize the information and conduct the study, six steps of the integrative review process were followed2222 Mendes KDS, Silveira RCCP, Galvão CM. Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enfermagem. Texto Contexto Enfermagem, 2008;17(4):758-64..

The first step involved identifying the topic and formulating the research guiding question. The second step was establishing inclusion and exclusion criteria, followed by a literature search in the selected databases. In the third step, the objective was to identify the selected studies. The fourth step involved categorizing the selected studies. The fifth step consisted of analyzing and discussing the results. Finally, in the sixth step, the integrative review was presented2323 Souza MT, Silva MD, Carvalho RD. Integrative review: what is it? How to do it? Einstein (São Paulo). 2010;8(1):102-6.. The search for the studies occurred in the following order: search of the databases using MeSH terms and keywords, reading of the titles, selection and reading of the abstracts of the pre-selected studies.

The guiding question for this review was: “What are the parameters used in transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) available in the literature for the treatment of chronic pelvic pain”?

The searches were conducted in six databases: Pubmed, Scielo, PEDro (Physiotherapy Evidence Database), Medline, Scopus (SciVerse Scopus), and Cochrane. The search terms used were “Pelvic Pain” for pelvic pain, “Transcranial direct current stimulation” for tDCS, and “Transcranial magnetic stimulation” for TMS, based on the Health Sciences Descriptors (DeCS) from the Virtual Health Library (BVS). The Boolean operator “AND” was used to combine the search terms.

Articles that presented duplicates between databases, were outside the 10-year period (January 2013 to May 2023) and were not clinical trials were excluded. The eligibility criteria included articles related to the topic and available in full text in Portuguese, English, or Spanish (figure 1 for tDCS and figure 2 for TMS).

Figure 1
Eligibility criteria included articles - tDCS

Figure 2
Eligibility criteria included articles - TMS

The extraction of data from the full reading was performed to fill a table with the eligibility criteria; after the final selection of studies, an integrative review with critical analysis of the results was performed.

RESULTS

The search yielded a total of 50 articles. However, after applying the eligibility criteria, only 7 articles were included in this review: 3 related to tDCS and 4 related to TMS. Among these, there were 2 pilot studies, 1 case study, 1 cross-sectional observational study, and 3 clinical trials. Several reasons led to the exclusion of the remaining articles, including their involvement with topics that did not align with the scope of this review, lack of significant relevance to the theme, studies that were already reviews themselves, studies that had not been conducted yet, as well as articles with restricted access or availability in languages other than Portuguese, English, or Spanish.

To present the findings, the included articles were grouped and structured. Table 1 contains the articles covering tDCS, while table 2 includes the articles selected for TMS.

Table 1
Data from selected Transcranial direct current stimulation articles
Table 2
Data from selected tramscranial magnetic stimulation articles

DISCUSSION

This study involved gathering data on the treatment of CPP using NIBS techniques: tDCS and TMS. The presented results highlight the scarcity of studies concerning the relationship between NIBS techniques and CPP. This scarcity may be attributed to the complex nature of CPP, which is a multifactorial condition with a challenging diagnosis of its etiology.

According to a study2121 Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, Jreige Iskandar A, Guerrero C, Amescua-García C, Kraychete DC, Caparelli-Daquer E, Atencio E, Piedimonte F, Colimon F, Hazime FA, Garcia JBS, Hernández-Castro JJ, Cantisani JAF, Karina do Monte-Silva K, Lemos Correia LC, Gallegos MS, Marcolin MA, Ricco MA, Cook MB, Bonilla P, Schestatsky P, Galhardoni R, Silva V, Delgado Barrera W, Caumo W, Bouhassira D, Chipchase LS, Lefaucheur JP, Teixeira MJ, de Andrade DC. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019 Jan 9;4(1):e692., addressing patients with CPP poses a challenge for healthcare professionals. It is often claimed that women with CPP have to live with the pain, and many professionals, unable to resolve the issue, become frustrated and label the patient’s pain as an emotional problem, subsequently abandoning the case. In this study, neuromodulation was considered as a potential intervention, as previous studies have suggested its potential to address not only pain but also other aspects such as sleep, cognitive complaints, fatigue, catastrophizing, depression, and mood2121 Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, Jreige Iskandar A, Guerrero C, Amescua-García C, Kraychete DC, Caparelli-Daquer E, Atencio E, Piedimonte F, Colimon F, Hazime FA, Garcia JBS, Hernández-Castro JJ, Cantisani JAF, Karina do Monte-Silva K, Lemos Correia LC, Gallegos MS, Marcolin MA, Ricco MA, Cook MB, Bonilla P, Schestatsky P, Galhardoni R, Silva V, Delgado Barrera W, Caumo W, Bouhassira D, Chipchase LS, Lefaucheur JP, Teixeira MJ, de Andrade DC. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019 Jan 9;4(1):e692..

The parameters of the most commonly used NIBS techniques for CPP are still subject to debate, and there may be divergent findings in the published studies. Regarding the stimulation area in TMS, a study1818 Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. mentioned the application on M1 and DLPFC, while another study2121 Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, Jreige Iskandar A, Guerrero C, Amescua-García C, Kraychete DC, Caparelli-Daquer E, Atencio E, Piedimonte F, Colimon F, Hazime FA, Garcia JBS, Hernández-Castro JJ, Cantisani JAF, Karina do Monte-Silva K, Lemos Correia LC, Gallegos MS, Marcolin MA, Ricco MA, Cook MB, Bonilla P, Schestatsky P, Galhardoni R, Silva V, Delgado Barrera W, Caumo W, Bouhassira D, Chipchase LS, Lefaucheur JP, Teixeira MJ, de Andrade DC. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019 Jan 9;4(1):e692. presented potential parameters for CPP treatment using an eight-shaped coil positioned over the M1 region. DLPFC plays a crucial role in cognitive and emotional processing, including pain modulation. It is involved in the cognitive control of pain, regulating attention, emotion, and pain-related cognitive processes.

Stimulation of the DLPFC can modulate the brain’s pain network, influencing pain perception and reducing pain intensity. The motor cortex is involved in the generation and modulation of pain signals. Stimulation of the M1 can modulate the excitability and activity of neural networks involved in pain processing and modulate the transmission of pain signals, altering pain perception. Two researchs2424 Pinot-Monange A, Moisset X, Chauvet P, Gremeau AS, Comptour A, Canis M, Pereira B, Bourdel N. Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study. J Clin Med. 2019;8(4):508.,2626 Nikkola J, Holm A, Seppänen M, Joutsi T, Rauhala E, Kaipia A. Repetitive transcranial magnetic stimulation for chronic prostatitis/chronic pelvic pain syndrome: a prospective pilot study. Int Neurourol J. 2020;24(2):144-9. conducted pilot studies and determined M1 as the target area for CPP treatment, supporting the guidelines proposed by another author1414 Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipović SR, Grefkes C, Hasan A, Hummel FC, Jääskeläinen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorová I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528.. Additionally, a study2525 Zakka TRM, Yeng LT, Teixeira MJ, Rosi Júnior J. Dor pélvica crônica não visceral: tratamento multidisciplinar. Relato de caso. Rev Dor. 2013;14(3):231-3. conducted an observational cross-sectional study using the M1 area and reported analgesic effects in the management of CPP.

Regarding the frequency used in TMS, the studies 2424 Pinot-Monange A, Moisset X, Chauvet P, Gremeau AS, Comptour A, Canis M, Pereira B, Bourdel N. Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study. J Clin Med. 2019;8(4):508.

25 Zakka TRM, Yeng LT, Teixeira MJ, Rosi Júnior J. Dor pélvica crônica não visceral: tratamento multidisciplinar. Relato de caso. Rev Dor. 2013;14(3):231-3.
-2626 Nikkola J, Holm A, Seppänen M, Joutsi T, Rauhala E, Kaipia A. Repetitive transcranial magnetic stimulation for chronic prostatitis/chronic pelvic pain syndrome: a prospective pilot study. Int Neurourol J. 2020;24(2):144-9. reached a consensus on using 10Hz for the management of CPP. As for determining the pulse width, two studies2424 Pinot-Monange A, Moisset X, Chauvet P, Gremeau AS, Comptour A, Canis M, Pereira B, Bourdel N. Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study. J Clin Med. 2019;8(4):508.,2626 Nikkola J, Holm A, Seppänen M, Joutsi T, Rauhala E, Kaipia A. Repetitive transcranial magnetic stimulation for chronic prostatitis/chronic pelvic pain syndrome: a prospective pilot study. Int Neurourol J. 2020;24(2):144-9. used 1,500 pulse trains per session, while another study2525 Zakka TRM, Yeng LT, Teixeira MJ, Rosi Júnior J. Dor pélvica crônica não visceral: tratamento multidisciplinar. Relato de caso. Rev Dor. 2013;14(3):231-3. opted for double that amount. All studies found positive effects on pain thresholds in their respective samples. Another parameter to consider is the pulse train duration and the intertrain interval. Two studies22 Calabrò RS, Billeri L, Porcari B, Pignolo L, Naro A. When two is better than one: a pilot study on transcranial magnetic stimulation plus muscle vibration in treating chronic pelvic pain in women. Brain Sci. 2022;12(3):396.,2626 Nikkola J, Holm A, Seppänen M, Joutsi T, Rauhala E, Kaipia A. Repetitive transcranial magnetic stimulation for chronic prostatitis/chronic pelvic pain syndrome: a prospective pilot study. Int Neurourol J. 2020;24(2):144-9. provided values for these parameters, with a ratio of 5s to 26s and 10s to 20s, respectively. Lastly, the resting motor threshold (RMT) and session duration were not specified by all authors, only by one2525 Zakka TRM, Yeng LT, Teixeira MJ, Rosi Júnior J. Dor pélvica crônica não visceral: tratamento multidisciplinar. Relato de caso. Rev Dor. 2013;14(3):231-3., who determined an RMT of 80% with a session duration of 15 minutes. In summary, all articles support the effectiveness and safety of TMS therapy as a viable alternative for the treatment of CPP.

Regarding tDCS, standardizing the target area is crucial to ensure the desired effects on pain thresholds. A double-blind controlled clinical study11 Divandari N, Manshadi FD, Shokouhi N, Vakili M, Jaberzadeh S. Effect of one session of tDCS on the severity of pain in women with chronic pelvic pain. J Bodyw Mov Ther. 2019;23(3):678-82. used M1 and DLPFC as target areas for CPP treatment, which resulted in a positive outcome in reducing pain thresholds. Additionally, a randomized clinical trial from 2016 used M1 and the contralateral side of the supraorbital area in a population with CPP, resulting in a significant and positive impact on sensory and pain thresholds2727 Simis M, Reidler JS, Duarte Macea D, Moreno Duarte I, Wang X, Lenkinski R, Petrozza JC, Fregni F. Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation. Pain Pract. 2015;15(5):423-32.. Also, a research2828 Harvey MP, Watier A, Dufort Rouleau É, Léonard G. Non-invasive stimulation techniques to relieve abdominal/pelvic pain: Is more always better? World J Gastroenterol. 2017;23(20):3758-60. combined tDCS with transcutaneous electrical nerve stimulation (TENS), with the application of tDCS in the contralateral M1 region to the pain and TENS in the lower abdominal and/or lumbar regions along with the tibial region. This combination did not yield additional benefits in patients with CPP based on the analysis of a single session.

Regarding amplitude, a study11 Divandari N, Manshadi FD, Shokouhi N, Vakili M, Jaberzadeh S. Effect of one session of tDCS on the severity of pain in women with chronic pelvic pain. J Bodyw Mov Ther. 2019;23(3):678-82. opted for 0.3mA, while another studies2727 Simis M, Reidler JS, Duarte Macea D, Moreno Duarte I, Wang X, Lenkinski R, Petrozza JC, Fregni F. Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation. Pain Pract. 2015;15(5):423-32.,2828 Harvey MP, Watier A, Dufort Rouleau É, Léonard G. Non-invasive stimulation techniques to relieve abdominal/pelvic pain: Is more always better? World J Gastroenterol. 2017;23(20):3758-60. chose 2mA. In terms of application time, only one study2828 Harvey MP, Watier A, Dufort Rouleau É, Léonard G. Non-invasive stimulation techniques to relieve abdominal/pelvic pain: Is more always better? World J Gastroenterol. 2017;23(20):3758-60. differed, with a session duration of 20 minutes, while the other authors utilized sessions of 30 minutes. Some of these findings align with the recommendations published in a study2121 Baptista AF, Fernandes AMBL, Sá KN, Okano AH, Brunoni AR, Lara-Solares A, Jreige Iskandar A, Guerrero C, Amescua-García C, Kraychete DC, Caparelli-Daquer E, Atencio E, Piedimonte F, Colimon F, Hazime FA, Garcia JBS, Hernández-Castro JJ, Cantisani JAF, Karina do Monte-Silva K, Lemos Correia LC, Gallegos MS, Marcolin MA, Ricco MA, Cook MB, Bonilla P, Schestatsky P, Galhardoni R, Silva V, Delgado Barrera W, Caumo W, Bouhassira D, Chipchase LS, Lefaucheur JP, Teixeira MJ, de Andrade DC. Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP). Pain Rep. 2019 Jan 9;4(1):e692., which suggests targeting the contralateral M1 or the dominant side as the target areas, using an amplitude of 2mA, and a session duration of 20 to 30 minutes.

The outcomes of the assessed studies often coincide, with the mentioned techniques showing potential for improving pain symptoms and enhancing the quality of life of participants, with minimal side effects. These findings underscore the relevance of NIBS techniques for CPP and emphasize the need for more randomized clinical trials involving larger populations.

NIBS is an innovative approach in the realm of neuroscientific research and treatment. This technique offers the capability to modulate brain activity without requiring surgical interventions or implantation of electrodes. While it holds immense promise, it’s essential to recognize its associated side effects. The most severe side effects reported are seizures and neurocardiogenic syncope. Minor side effects include headache, scalp discomfort, twitching, fatigue, and tinnitus. However, in the broader context, it’s worth noting that these side effects are relatively few and most are transient2626 Nikkola J, Holm A, Seppänen M, Joutsi T, Rauhala E, Kaipia A. Repetitive transcranial magnetic stimulation for chronic prostatitis/chronic pelvic pain syndrome: a prospective pilot study. Int Neurourol J. 2020;24(2):144-9..

The studies included in this review were limited in scope and sample size, often involving only a single session of NIBS. It is necessary to conduct more well-designed, large-scale randomized controlled trials with broader populations, multiple treatment sessions, and long-term follow-ups to establish more reliable parameter relationships. In addition, a limited number of publications on the theme was identified, making this review difficult to carry out, even considering the limitations inherent in the methodology used in an integrative review.

CONCLUSION

NIBS techniques, particularly when targeting the M1 cortex, emerge as a promising avenue for alleviating CPP. The studies reviewed in this paper demonstrate significant improvements in pain levels and overall QoL for patients. Specifically, the M1 cortex has been frequently utilized, underlining its potential relevance in managing CPP. However, despite these encouraging results, there remains a lack of consensus on the precise parameters for using techniques like TMS and tDCS specifically for CPP. As the field advances, further research is imperative to optimize and standardize these parameters, ensuring both efficacy and safety for patients.

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Publication Dates

  • Publication in this collection
    23 Oct 2023
  • Date of issue
    Jul-Sep 2023

History

  • Received
    07 June 2023
  • Accepted
    28 Aug 2023
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