The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain.

BACKGROUND: Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. METHODS: Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. RESULTS: Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. CONCLUSION: Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

ANTECEDENTES: A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. MéTODOS: Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. RESULTADOS: Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. CONCLUSãO: A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain / O efeito da dexmedetomidina na expressão do óxido nítrico sintase neuronal na medula espinhal dorsal em um modelo rato com dor neuropática crônica

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

Resumo Antecedentes A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. Métodos Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. Resultados Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. Conclusão A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

LONG-TERM OUTCOMES OF LIGATION OF INTERSPHINCTERIC FISTULA TRACT FOR COMPLEX FISTULA-IN-ANO: MODIFIED OPERATIVE PROCEDURE EXPERIENCE.

BACKGROUND: It is important but difficult to treat complex fistula-in-ano due to the high recurrent rate and following incontinence. Ligation of the intersphincteric fistula tract (LIFT), a novel surgical procedure with the advantage of avoiding anal incontinence, has a variable success rate of 57-94.4 %. AIM: To evaluate the long-term outcomes of modified LIFT operative procedure - ligation of intersphincteric fistula tract - to treat complex fistula-in-ano. METHODS: Retrospective analysis of 62 cases of complex fistula-in-ano. The group was treated with the modified approach of LIFT (curved incision was made in the anal canal skin; purse-string suture was performed around the fistula; the residual fistulas were removed in a tunnel-based way) and had a follow-up time of more than one year. Patient´s preoperative general condition, postoperative efficacy and their anal function were compared. RESULTS: The median age of the participants was 34, and 43 (69.4%) cases were male. Forty-one (66.1%) cases were of high transsphincteric fistula, four (6.5%) cases of high intrasphincter fistula, and 17 (27.4%) cases of anterior anal fistula in female. The median follow-up duration was 24.5 (range, 12-51) months. The success rate in the end of follow-up was 83.9% (52/62). The anorectal pressure and Cleveland Clinic Florida Fecal Incontinence (CCF-FI) evaluated three months before and after the operation did not find apparent changes. CONCLUSIONS: Compared with LIFT, the modified LIFT remarkably reduces postoperative failure and the recurrence rate of complex fistula with acceptable long-term outcomes.

Long-term outcomes of ligation of intersphincteric fistula tract for complex fistula-in-ano: modified operative procedure experience / Resultados em longo prazo da ligadura da fístula interesfincteriana no complexo das fístulas perianais: modificação técnica de procedimento cirúrgico

ABSTRACT Background: It is important but difficult to treat complex fistula-in-ano due to the high recurrent rate and following incontinence. Ligation of the intersphincteric fistula tract (LIFT), a novel surgical procedure with the advantage of avoiding anal incontinence, has a variable success rate of 57-94.4 %. Aim: To evaluate the long-term outcomes of modified LIFT operative procedure - ligation of intersphincteric fistula tract - to treat complex fistula-in-ano. Methods: Retrospective analysis of 62 cases of complex fistula-in-ano. The group was treated with the modified approach of LIFT (curved incision was made in the anal canal skin; purse-string suture was performed around the fistula; the residual fistulas were removed in a tunnel-based way) and had a follow-up time of more than one year. Patient´s preoperative general condition, postoperative efficacy and their anal function were compared. Results: The median age of the participants was 34, and 43 (69.4%) cases were male. Forty-one (66.1%) cases were of high transsphincteric fistula, four (6.5%) cases of high intrasphincter fistula, and 17 (27.4%) cases of anterior anal fistula in female. The median follow-up duration was 24.5 (range, 12-51) months. The success rate in the end of follow-up was 83.9% (52/62). The anorectal pressure and Cleveland Clinic Florida Fecal Incontinence (CCF-FI) evaluated three months before and after the operation did not find apparent changes. Conclusions: Compared with LIFT, the modified LIFT remarkably reduces postoperative failure and the recurrence rate of complex fistula with acceptable long-term outcomes.

RESUMO Racional: É importante, mas difícil de se tratar fístula anal complexa devido à alta taxa de recorrência e de incontinência pós-operatória. A ligadura do trajeto da fístula interesfincteriana (LIFT) - um novo procedimento cirúrgico com a vantagem de evitar a incontinência anal - tem taxa de sucesso variável entre 57-94,4%. Objetivo: Avaliar os resultados em longo prazo do procedimento cirúrgico LIFT modificado - ligadura do trato interesfincteriano com fístula - para tratar fístula complexa anal. Métodos: Análise retrospectiva de 62 casos de fístula complexa no ânus tratados com abordagem modificada de LIFT (incisão curva na pele do canal anal; sutura em bolsa realizada em torno da fístula; as fístulas residuais removidas em um túnel) e teve tempo de acompanhamento de mais de um ano. A condição geral pré-operatória dos pacientes, a eficácia pós-operatória e a função anal foram comparadas. Resultados: A mediana de idade dos participantes foi de 34 anos, e 43 (69,4%) dos casos eram de homens. Quarenta e um (66,1%) casos eram de fístula transesfincteriana alta, quatro (6,5%) de fístula intra-esfincteriana alta e 17 (27,4%) de fístula anal anterior em mulheres. A mediana da duração do acompanhamento foi de 24,5 meses (12-51). A taxa de sucesso no final do acompanhamento foi de 83,9% (52/62). A pressão anorretal e a Incontinência Fecal da Cleveland Clinic Florida (CCF-FI) avaliadas três meses antes e após a operação não encontraram alterações aparentes. Conclusões: Comparado com o LIFT, o LIFT modificado reduz notavelmente a falha pós-operatória e a taxa de recorrência de fístula complexa com resultados aceitáveis em longo prazo.