Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido

Detalhes bibliográficos
Autor(a) principal: Holanda, Vanessa Milanesi
Data de Publicação: 2016
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
Texto Completo: http://bibliotecatede.uninove.br/handle/tede/2780
Resumo: Chronic axial low back pain is a complicated drawback in public health and has a high so- cioeconomic impact. OBJECTIVE: The aim of this study were to determine the response of laser irradiation in the dorsal root ganglion of the second lumbar spinal nerve for chronic axial low back pain compared to lidocaine injection and radiofrequency treatment and its mechanistic basis of photobiomodulation therapy for low back pain. MATERIAL and METHODS: This study was divided in PART I: Experimental studies which took place at the Department of Anatomy, Physi- ology and Genetics at the Uniformed Services University of the Health Sciences (USUHS), Bethes- da, Maryland, USA.; and PART II: Clinical study developed at Beneficência Portuguesa Hospital of São Paulo, Brazil. PART I: In vitro study: Rat DRG neurons were seeded and cultured on coat- ed slides for 48 hours. The cultures were randomly assigned to either control or to laser treatment (LT) groups for 2, 5, 30, 60 or 120s. The laser parameters were: output power= 960mW, power density= 300mW/cm2, 808nm wavelength, spot size= 3cm diameter and area= 7,07cm2. Forty minutes post laser, the MTS assay was applied to measure mitochondrial metabolic activity. Cells were also fixed with paraformaldehyde for immunocytochemistry with an antibody to β-Tubulin III visualized and photographed using fluorescence microscopy. In vivo study: 12 rats were divid- ed into three groups (n=4): 1) Control: surgery without LT, 2) Short term: surgery for spared nerve injury of common peroneal and tibial nerves with LT on day 7 and euthanized on day 7 af- ter behavior test, 3) Long term: surgery with LT on day 7 and euthanized on day 22. PART II: Clinical prospective, control, randomized study, in which thirty-one patients were divided into three treatment groups: G1) lidocaine injection, G2) radiofrequency, or G3) lasertherapy irradia- tion. The second intervertebral foramen between the second and third lumbar vertebrae was ac- cessed by percutaneous needle puncture bilaterally, guided by fluoroscopy. In the local anesthetic group, 1ml lidocaine injection without epinephrine was used through a 20-gauge (G20) quincke tip spinal needle inserted in the second lumbar intervertebral foramen. In the radiofrequency group, the probe (150mm long with a 5mm active tip) was directed through a G20 needle placed in the second lumbar intervertebral foramen and a pulsed radiofrequency neuromodulation was done, using Cosman G4® in pulses of 20ms with wash-out period of 480 ms, for 300 seconds at 42oC. In all groups a single treatment was applied. In the laser treatment group, a continuous wave (CW), 808nm wavelength diode laser (Photon Lase III® DCM, Brazil), with an output power of 100mW was used for a single treatment. An 18 gauge needle was placed in the second lumbar intervertebral foramen guided by fluoroscopy. Light irradiation was delivered through a 600μm optical fiber placed in the G18 needle. The tip of the fiber extended 5mm beyond the tip of the needle in the second lumbar intervertebral foramen. The beam spot size was 0.003cm2, irradiance = 35W/cm2, exposure time = 84 seconds, energy density = 2,800J/cm2, total energy was 8,4 J. The low back pain score was assessed by the visual analog scale (VAS) and Pain Relief Scale (PRS) pre, post procedure, in 1 and 12 months follow up. Temperature was measured using a digital ther- mometer. RESULTS: PART I: All the LT groups had statistically significant lower mitochondrial metabolism compared to controls. Within neuritis of DRG neurons with a diameter 30μm or less, varicosities and undulations were present. These neurons are associated with C and Aδ fiber types. The neuritis of DRG neurons with a diameter of greater than 30μm initiated to form vari- cosities only in the 120s group. For heat hyperalgesia, no significant difference was found between control and LT groups on 7 days post-injury. Within 1 hour post LT, the injured site presented significant less sensitivity to the heat stimulus compared to the ones before LT. For long term, LT causes less sensitivity to the heat stimulus than control group on Day 15 and Day 21. For cold al- lodynia, the injured site displayed significant less sensitivity to the cold stimulus within 1 hour after LT. For long term, the sensitivity to the cold stimulus returned to the control level after 5 days post-LT (Day 12). For mechanical hyperalgesia, the injured site indicated significant less sen- sitivity to the pin prick stimulus within 1 hour after irradiation with LT. For long term, the sensi- tivity to the pin prick stimulus also returned to the control level after 5 days post-LT on Day 12. For mechanical allodynia using electronic Von Frey test, no significant difference was seen for both immediate effect and long-term effect of LT between control and LT group. PART II: All patients in the local anesthetic and laser treatment groups reported a pain reduction of at least 50% immediately post-procedure and 10 out of 11 patients in the radiofrequency group reported a pain reduction of at least 50%. At 1 month post-treatment, the laser treatment group had the greatest number of patients who reported more than 50% pain relief, based on PRS (7 out of 10 patients), while only 5 out of 10 patients and 3 out of 11 patients in the lidocaine and radiofre- quency treatment groups, respectively, reported more than a 50% pain relief. In the radiofre- quency treatment group, for long term follow up (1 year), all the patients evaluated (9 out of 9) increased their pain to the same level to the previous procedure and also could not return to their daily life activities. In the lidocaine group, 1 out of 8 patients reported 50% pain relief based on PRS and this patient returned to his daily life activities. In the laser group, 4 out of 7 patients de- scribed more than 50% on PRS, but just one of them returned to her daily life activities, the other complained about disabled hip joint pain. Both patients considered themselves satisfied with the procedure, then pointing general improvement of their quality of life. CONCLUSION: Photobio- modulation therapy of the second lumbar dorsal root ganglion revealed a successful and long- lasting pain control when compared to lidocaine and pulsed radiofrequency. The decrease in mi- tochondrial metabolism and associated morphological changes in the neuritis may be directly re- lated to the mechanistic basis of photoneuromodulation of chronic low back pain observed clini- cally. This long-lasting conduction blockage presented in the clinical study is related to the mor- phological changes based on the components of the cytoskeleton of the different types of neurons, due to the use of a high-level irradiance in the interval of 270-300mW/cm2. Laser irradiation was more effective than the other two treatments employed, for long term chronic low back pain con- trol, without side-effects, and with cost-effectiveness.
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spelling Chavantes, Maria Cristinahttp://lattes.cnpq.br/9684711829191051Chavantes, Maria Cristinahttp://lattes.cnpq.br/9684711829191051Zamuner, Stella Reginahttp://lattes.cnpq.br/1935805744318404Marcos, Rodrigo Labathttp://lattes.cnpq.br/2964112163504080Anders, Juanita JZamorano, Luciahttp://lattes.cnpq.br/4951035987063239Holanda, Vanessa Milanesi2021-11-25T18:13:16Z2016-11-04Holanda, Vanessa Milanesi. Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido. 2016. 114 f. Tese( Programa de Pós-Graduação em Biofotônica Aplicada às Ciências da Saúde) - Universidade Nove de Julho, São Paulo.http://bibliotecatede.uninove.br/handle/tede/2780Chronic axial low back pain is a complicated drawback in public health and has a high so- cioeconomic impact. OBJECTIVE: The aim of this study were to determine the response of laser irradiation in the dorsal root ganglion of the second lumbar spinal nerve for chronic axial low back pain compared to lidocaine injection and radiofrequency treatment and its mechanistic basis of photobiomodulation therapy for low back pain. MATERIAL and METHODS: This study was divided in PART I: Experimental studies which took place at the Department of Anatomy, Physi- ology and Genetics at the Uniformed Services University of the Health Sciences (USUHS), Bethes- da, Maryland, USA.; and PART II: Clinical study developed at Beneficência Portuguesa Hospital of São Paulo, Brazil. PART I: In vitro study: Rat DRG neurons were seeded and cultured on coat- ed slides for 48 hours. The cultures were randomly assigned to either control or to laser treatment (LT) groups for 2, 5, 30, 60 or 120s. The laser parameters were: output power= 960mW, power density= 300mW/cm2, 808nm wavelength, spot size= 3cm diameter and area= 7,07cm2. Forty minutes post laser, the MTS assay was applied to measure mitochondrial metabolic activity. Cells were also fixed with paraformaldehyde for immunocytochemistry with an antibody to β-Tubulin III visualized and photographed using fluorescence microscopy. In vivo study: 12 rats were divid- ed into three groups (n=4): 1) Control: surgery without LT, 2) Short term: surgery for spared nerve injury of common peroneal and tibial nerves with LT on day 7 and euthanized on day 7 af- ter behavior test, 3) Long term: surgery with LT on day 7 and euthanized on day 22. PART II: Clinical prospective, control, randomized study, in which thirty-one patients were divided into three treatment groups: G1) lidocaine injection, G2) radiofrequency, or G3) lasertherapy irradia- tion. The second intervertebral foramen between the second and third lumbar vertebrae was ac- cessed by percutaneous needle puncture bilaterally, guided by fluoroscopy. In the local anesthetic group, 1ml lidocaine injection without epinephrine was used through a 20-gauge (G20) quincke tip spinal needle inserted in the second lumbar intervertebral foramen. In the radiofrequency group, the probe (150mm long with a 5mm active tip) was directed through a G20 needle placed in the second lumbar intervertebral foramen and a pulsed radiofrequency neuromodulation was done, using Cosman G4® in pulses of 20ms with wash-out period of 480 ms, for 300 seconds at 42oC. In all groups a single treatment was applied. In the laser treatment group, a continuous wave (CW), 808nm wavelength diode laser (Photon Lase III® DCM, Brazil), with an output power of 100mW was used for a single treatment. An 18 gauge needle was placed in the second lumbar intervertebral foramen guided by fluoroscopy. Light irradiation was delivered through a 600μm optical fiber placed in the G18 needle. The tip of the fiber extended 5mm beyond the tip of the needle in the second lumbar intervertebral foramen. The beam spot size was 0.003cm2, irradiance = 35W/cm2, exposure time = 84 seconds, energy density = 2,800J/cm2, total energy was 8,4 J. The low back pain score was assessed by the visual analog scale (VAS) and Pain Relief Scale (PRS) pre, post procedure, in 1 and 12 months follow up. Temperature was measured using a digital ther- mometer. RESULTS: PART I: All the LT groups had statistically significant lower mitochondrial metabolism compared to controls. Within neuritis of DRG neurons with a diameter 30μm or less, varicosities and undulations were present. These neurons are associated with C and Aδ fiber types. The neuritis of DRG neurons with a diameter of greater than 30μm initiated to form vari- cosities only in the 120s group. For heat hyperalgesia, no significant difference was found between control and LT groups on 7 days post-injury. Within 1 hour post LT, the injured site presented significant less sensitivity to the heat stimulus compared to the ones before LT. For long term, LT causes less sensitivity to the heat stimulus than control group on Day 15 and Day 21. For cold al- lodynia, the injured site displayed significant less sensitivity to the cold stimulus within 1 hour after LT. For long term, the sensitivity to the cold stimulus returned to the control level after 5 days post-LT (Day 12). For mechanical hyperalgesia, the injured site indicated significant less sen- sitivity to the pin prick stimulus within 1 hour after irradiation with LT. For long term, the sensi- tivity to the pin prick stimulus also returned to the control level after 5 days post-LT on Day 12. For mechanical allodynia using electronic Von Frey test, no significant difference was seen for both immediate effect and long-term effect of LT between control and LT group. PART II: All patients in the local anesthetic and laser treatment groups reported a pain reduction of at least 50% immediately post-procedure and 10 out of 11 patients in the radiofrequency group reported a pain reduction of at least 50%. At 1 month post-treatment, the laser treatment group had the greatest number of patients who reported more than 50% pain relief, based on PRS (7 out of 10 patients), while only 5 out of 10 patients and 3 out of 11 patients in the lidocaine and radiofre- quency treatment groups, respectively, reported more than a 50% pain relief. In the radiofre- quency treatment group, for long term follow up (1 year), all the patients evaluated (9 out of 9) increased their pain to the same level to the previous procedure and also could not return to their daily life activities. In the lidocaine group, 1 out of 8 patients reported 50% pain relief based on PRS and this patient returned to his daily life activities. In the laser group, 4 out of 7 patients de- scribed more than 50% on PRS, but just one of them returned to her daily life activities, the other complained about disabled hip joint pain. Both patients considered themselves satisfied with the procedure, then pointing general improvement of their quality of life. CONCLUSION: Photobio- modulation therapy of the second lumbar dorsal root ganglion revealed a successful and long- lasting pain control when compared to lidocaine and pulsed radiofrequency. The decrease in mi- tochondrial metabolism and associated morphological changes in the neuritis may be directly re- lated to the mechanistic basis of photoneuromodulation of chronic low back pain observed clini- cally. This long-lasting conduction blockage presented in the clinical study is related to the mor- phological changes based on the components of the cytoskeleton of the different types of neurons, due to the use of a high-level irradiance in the interval of 270-300mW/cm2. Laser irradiation was more effective than the other two treatments employed, for long term chronic low back pain con- trol, without side-effects, and with cost-effectiveness.A dor lombar crônica é um problema de Saúde Pública com um importante impacto socioeconômico. Vários estudos na literatura relatam que o laser de baixa intensidade (LBI) é eficaz para ajuda no alívio da dor, seja ela aguda ou crônica. O objetivo desse estudo foi determinar o efeito do LBI, quando aplicado no gânglio da segunda raiz dorsal (GRD) para auxiliar no tratamento da dor lombar crônica. Metodologia: O estudo foi dividido em PARTE I: Estudos in vitro e in vivo desenvolvidos no Department of Anatomy, Physiology and Genetics da Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USA; e PARTE II: Estudo clínico realizado no Hospital Beneficência Portuguesa de São Paulo pela Universidade Nove de Julho (UNINOVE). PARTE I: Subdividida em 2 etapas: Estudo celular e posteriormente ensaio experimental in vivo, a fim de entender os mecanismos envolvidos no uso da fotobiomodulação para tratar a dor, através da aplicação do laser no GRD. No estudo in vitro, neurônios de rato DRG foram semeadas e cultivadas em lâminas revestidas durante 48 horas. As culturas foram aleatoriamente designadas, como controle ou grupos de 2, 5, 30, 60 ou 120s tratamento à laser (TL). Os parâmetros do laser foram: potência = 960mW, densidade de potência = 300mW/cm2 e comprimento de onda () = 808nm. Após 40 minutos da aplicação do laser, o ensaio MTS foi empregado a fim de se medir a atividade metabólica mitocondrial. As células foram fixadas para imunocitoquímica anti β-tubulina III, visualizadas e fotografadas, com microscopia de fluorescência. Estudo in vivo: 12 ratos foram divididos em três grupos (n = 4): controle (GC); cirurgia com TL curto prazo (GP): cirurgia para lesão dos nervos fibular comum e tibial, com TL no dia 7 e sacrificados ainda no dia 7 logo após o teste de comportamento, bem como a longo prazo (GL): cirurgia com TL no dia 7 e sacrificados no dia 22. PARTE II: Estudo clínico, randomizado com 31 pacientes que foram divididos em três grupos: G1: lidocaína; G2: radiofrequência; e G3: laser, avaliados prospectivamente. O acesso bilateral percutâneo com agulha guiado por radioscopia para localizar o segundo espaço intervertebral (2IV). Grupo 1: anestésico local, injeção de 1 ml de lidocaína aplicada na cânula de 20-gauge (G20), em contato com o alvo. Grupo 2: radiofrequência, o eletrodo foi direcionado através de uma agulha G20 no 2IV, sendo realizada neuromodulação com o uso da radiofrequência em pulsos de 20ms com um período de repouso de 480ms, por 300 s, a 42oC. Esse único tratamento foi realizado, bilateralmente. No grupo 3: laser, foi aplicado o CW laser de diodo com 808nm de comprimento de onda (Photon Lase III®, DCM, Brasil), com uma potência de 100mW para um único tratamento por 84 segundos. Uma agulha de 18 gauge foi posicionada no 2IV guiada por radioscopia. O laser foi administrado através de uma fibra óptica de 600μm que passava no interior da agulha G18. A ponta do laser foi fixada e ultrapassava em 5mm a ponta da agulha dentro do forame intervertebral. A irradiância do laser foi de 35W/cm2, densidade de energia = 2.800J/cm2, energia total = 8.4J. Através da escala visual analógica (EVA) e da escala de alívio da dor (EAD), a intensidade da dor foi avaliada pré, pós procedimento e no follow up de 1 e 12 meses. A temperatura foi avaliada através de um termômetro digital. Foram coletadas amostras do aspirado periganglionar para estudo de IL-1β e TNF-, avaliadas por ELISA. Resultados: PARTE I- Estudo in vitro: Todos os grupos de tratamento à laser (TL) apresentaram redução do metabolismo mitocondrial em relação ao controle. Neurites estavam presentes, com varicosidades e ondulações, nos neurônios do GRD com 30μm de diâmetro ou menos. Esses neurônios estão associados às fibras (finas e médio diâmetro) C e Aδ. As neurites nos neurônios do GRD com um diâmetro > 30μm começaram a formar varicosidades somente no grupo de 120s. Estudo in vivo: Para hiperalgesia ao calor, não houve diferença entre os grupos controle e TL nos 7 dias pós- lesão. A curto prazo, 1 hora após o TL, o local lesionado mostrou menor sensibilidade ao estímulo térmico. Para longo prazo, TL denotou menor sensibilidade ao estímulo de calor do que o grupo controle no dia 15 e dia 21. Para alodínia ao frio, o local lesionado mostrou menor sensibilidade ao estímulo frio dentro de 1 hora após a TL. A sensibilidade ao estímulo frio retornou ao nível do controle após 5 dias da TL. Para hiperalgesia mecânica, o local lesionado demonstrou menor sensibilidade aos estímulos de picada com agulha no prazo de 1 hora após a TL. A sensibilidade ao estímulo da picada da agulha também retornou ao nível do controle após 5 dias do tratamento. Para alodínia mecânica, nenhuma diferença foi observada tanto para efeito imediato quanto a longo prazo entre grupo controle e TL. PARTE II- Estudo Clínico: Todos os pacientes dos grupos anestésico local e laser relataram uma redução da dor de pelo menos 50% após os procedimentos e 10 de 11 pacientes o grupo de radiofrequência relataram essa melhora. Contudo, 1 mês pós- tratamento, o grupo laser apresentou o maior número de pacientes, que relataram mais de 50% de alívio da dor com base na EAD (7 de 10 pacientes), enquanto apenas 2 de 7 pacientes e 3 de 11 pacientes nos grupos lidocaína e radiofrequência, respectivamente, referiram mais de 50% de alívio da dor. No follow up de 12 meses, o grupo laser permaneceu com maior número de pacientes com manutenção da melhora de mais de 50% da dor (4 de 7 pacientes), enquanto 0 de 8 pacientes no grupo lidocaína e 0 de 9 pacientes no grupo radiofrequência. Conclusão: A laserterapia, quando comparada à administração de lidocaína e ao uso da radiofrequência aplicados no GRD do segundo nervo lombar (L2), revelou analgesia mais duradoura, sem qualquer efeito adverso. O bloqueio de condução de longa duração apresentado neste estudo clínico pode ser confirmado pelas às alterações morfológicas transitórias do citoesqueleto dos diferentes devido à utilização de um elevado nível de energia, com a densidade de potência de 270- 300mW/cm2. Esses resultados validam que o laser de baixa intensidade com os respectivos parâmetros otimizados foi eficaz, seguro, com efeito prolongado e bom custo-benefício para paciente portador de dor neuropática lombar crônica, melhorando a qualidade de vida destes, quando submetidos à terapia fotobiomodulação.Submitted by Nadir Basilio (nadirsb@uninove.br) on 2021-11-25T18:13:16Z No. of bitstreams: 1 Vanessa Milanesi Holanda.pdf: 3057857 bytes, checksum: 04dd815c6d05f1171420039851e49198 (MD5)Made available in DSpace on 2021-11-25T18:13:16Z (GMT). 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dc.title.por.fl_str_mv Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
dc.title.alternative.eng.fl_str_mv Photobiomodulation of the dorsal root ganglion to treat low back pain: clinical and experimental studies to determine the mechanism basis
title Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
spellingShingle Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
Holanda, Vanessa Milanesi
fotobiomodulação
laserterapia
controle da dor neuropática
gânglio da raiz dorsal
dor lombar crônica
photobiomodulation
laser therapy
neuropathic pain control
dorsal root gan- glion
chronic low back pain
CIENCIAS DA SAUDE
title_short Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
title_full Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
title_fullStr Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
title_full_unstemmed Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
title_sort Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido
author Holanda, Vanessa Milanesi
author_facet Holanda, Vanessa Milanesi
author_role author
dc.contributor.advisor1.fl_str_mv Chavantes, Maria Cristina
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9684711829191051
dc.contributor.referee1.fl_str_mv Chavantes, Maria Cristina
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/9684711829191051
dc.contributor.referee2.fl_str_mv Zamuner, Stella Regina
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/1935805744318404
dc.contributor.referee3.fl_str_mv Marcos, Rodrigo Labat
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/2964112163504080
dc.contributor.referee4.fl_str_mv Anders, Juanita J
dc.contributor.referee5.fl_str_mv Zamorano, Lucia
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4951035987063239
dc.contributor.author.fl_str_mv Holanda, Vanessa Milanesi
contributor_str_mv Chavantes, Maria Cristina
Chavantes, Maria Cristina
Zamuner, Stella Regina
Marcos, Rodrigo Labat
Anders, Juanita J
Zamorano, Lucia
dc.subject.por.fl_str_mv fotobiomodulação
laserterapia
controle da dor neuropática
gânglio da raiz dorsal
dor lombar crônica
topic fotobiomodulação
laserterapia
controle da dor neuropática
gânglio da raiz dorsal
dor lombar crônica
photobiomodulation
laser therapy
neuropathic pain control
dorsal root gan- glion
chronic low back pain
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv photobiomodulation
laser therapy
neuropathic pain control
dorsal root gan- glion
chronic low back pain
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Chronic axial low back pain is a complicated drawback in public health and has a high so- cioeconomic impact. OBJECTIVE: The aim of this study were to determine the response of laser irradiation in the dorsal root ganglion of the second lumbar spinal nerve for chronic axial low back pain compared to lidocaine injection and radiofrequency treatment and its mechanistic basis of photobiomodulation therapy for low back pain. MATERIAL and METHODS: This study was divided in PART I: Experimental studies which took place at the Department of Anatomy, Physi- ology and Genetics at the Uniformed Services University of the Health Sciences (USUHS), Bethes- da, Maryland, USA.; and PART II: Clinical study developed at Beneficência Portuguesa Hospital of São Paulo, Brazil. PART I: In vitro study: Rat DRG neurons were seeded and cultured on coat- ed slides for 48 hours. The cultures were randomly assigned to either control or to laser treatment (LT) groups for 2, 5, 30, 60 or 120s. The laser parameters were: output power= 960mW, power density= 300mW/cm2, 808nm wavelength, spot size= 3cm diameter and area= 7,07cm2. Forty minutes post laser, the MTS assay was applied to measure mitochondrial metabolic activity. Cells were also fixed with paraformaldehyde for immunocytochemistry with an antibody to β-Tubulin III visualized and photographed using fluorescence microscopy. In vivo study: 12 rats were divid- ed into three groups (n=4): 1) Control: surgery without LT, 2) Short term: surgery for spared nerve injury of common peroneal and tibial nerves with LT on day 7 and euthanized on day 7 af- ter behavior test, 3) Long term: surgery with LT on day 7 and euthanized on day 22. PART II: Clinical prospective, control, randomized study, in which thirty-one patients were divided into three treatment groups: G1) lidocaine injection, G2) radiofrequency, or G3) lasertherapy irradia- tion. The second intervertebral foramen between the second and third lumbar vertebrae was ac- cessed by percutaneous needle puncture bilaterally, guided by fluoroscopy. In the local anesthetic group, 1ml lidocaine injection without epinephrine was used through a 20-gauge (G20) quincke tip spinal needle inserted in the second lumbar intervertebral foramen. In the radiofrequency group, the probe (150mm long with a 5mm active tip) was directed through a G20 needle placed in the second lumbar intervertebral foramen and a pulsed radiofrequency neuromodulation was done, using Cosman G4® in pulses of 20ms with wash-out period of 480 ms, for 300 seconds at 42oC. In all groups a single treatment was applied. In the laser treatment group, a continuous wave (CW), 808nm wavelength diode laser (Photon Lase III® DCM, Brazil), with an output power of 100mW was used for a single treatment. An 18 gauge needle was placed in the second lumbar intervertebral foramen guided by fluoroscopy. Light irradiation was delivered through a 600μm optical fiber placed in the G18 needle. The tip of the fiber extended 5mm beyond the tip of the needle in the second lumbar intervertebral foramen. The beam spot size was 0.003cm2, irradiance = 35W/cm2, exposure time = 84 seconds, energy density = 2,800J/cm2, total energy was 8,4 J. The low back pain score was assessed by the visual analog scale (VAS) and Pain Relief Scale (PRS) pre, post procedure, in 1 and 12 months follow up. Temperature was measured using a digital ther- mometer. RESULTS: PART I: All the LT groups had statistically significant lower mitochondrial metabolism compared to controls. Within neuritis of DRG neurons with a diameter 30μm or less, varicosities and undulations were present. These neurons are associated with C and Aδ fiber types. The neuritis of DRG neurons with a diameter of greater than 30μm initiated to form vari- cosities only in the 120s group. For heat hyperalgesia, no significant difference was found between control and LT groups on 7 days post-injury. Within 1 hour post LT, the injured site presented significant less sensitivity to the heat stimulus compared to the ones before LT. For long term, LT causes less sensitivity to the heat stimulus than control group on Day 15 and Day 21. For cold al- lodynia, the injured site displayed significant less sensitivity to the cold stimulus within 1 hour after LT. For long term, the sensitivity to the cold stimulus returned to the control level after 5 days post-LT (Day 12). For mechanical hyperalgesia, the injured site indicated significant less sen- sitivity to the pin prick stimulus within 1 hour after irradiation with LT. For long term, the sensi- tivity to the pin prick stimulus also returned to the control level after 5 days post-LT on Day 12. For mechanical allodynia using electronic Von Frey test, no significant difference was seen for both immediate effect and long-term effect of LT between control and LT group. PART II: All patients in the local anesthetic and laser treatment groups reported a pain reduction of at least 50% immediately post-procedure and 10 out of 11 patients in the radiofrequency group reported a pain reduction of at least 50%. At 1 month post-treatment, the laser treatment group had the greatest number of patients who reported more than 50% pain relief, based on PRS (7 out of 10 patients), while only 5 out of 10 patients and 3 out of 11 patients in the lidocaine and radiofre- quency treatment groups, respectively, reported more than a 50% pain relief. In the radiofre- quency treatment group, for long term follow up (1 year), all the patients evaluated (9 out of 9) increased their pain to the same level to the previous procedure and also could not return to their daily life activities. In the lidocaine group, 1 out of 8 patients reported 50% pain relief based on PRS and this patient returned to his daily life activities. In the laser group, 4 out of 7 patients de- scribed more than 50% on PRS, but just one of them returned to her daily life activities, the other complained about disabled hip joint pain. Both patients considered themselves satisfied with the procedure, then pointing general improvement of their quality of life. CONCLUSION: Photobio- modulation therapy of the second lumbar dorsal root ganglion revealed a successful and long- lasting pain control when compared to lidocaine and pulsed radiofrequency. The decrease in mi- tochondrial metabolism and associated morphological changes in the neuritis may be directly re- lated to the mechanistic basis of photoneuromodulation of chronic low back pain observed clini- cally. This long-lasting conduction blockage presented in the clinical study is related to the mor- phological changes based on the components of the cytoskeleton of the different types of neurons, due to the use of a high-level irradiance in the interval of 270-300mW/cm2. Laser irradiation was more effective than the other two treatments employed, for long term chronic low back pain con- trol, without side-effects, and with cost-effectiveness.
publishDate 2016
dc.date.issued.fl_str_mv 2016-11-04
dc.date.accessioned.fl_str_mv 2021-11-25T18:13:16Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv Holanda, Vanessa Milanesi. Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido. 2016. 114 f. Tese( Programa de Pós-Graduação em Biofotônica Aplicada às Ciências da Saúde) - Universidade Nove de Julho, São Paulo.
dc.identifier.uri.fl_str_mv http://bibliotecatede.uninove.br/handle/tede/2780
identifier_str_mv Holanda, Vanessa Milanesi. Análise da resposta da fotobiomodulação no gânglio da raiz dorsal para tratamento da dor lombar crônica: estudo clínico e experimental na determinação do mecanismo de ação envolvido. 2016. 114 f. Tese( Programa de Pós-Graduação em Biofotônica Aplicada às Ciências da Saúde) - Universidade Nove de Julho, São Paulo.
url http://bibliotecatede.uninove.br/handle/tede/2780
dc.language.iso.fl_str_mv por
language por
dc.relation.cnpq.fl_str_mv 8765449414823306929
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Universidade Nove de Julho
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Biofotônica Aplicada às Ciências da Saúde
dc.publisher.initials.fl_str_mv UNINOVE
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Saúde
publisher.none.fl_str_mv Universidade Nove de Julho
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