418 THE CLINICAL AND LABORATORIAL EVALUATION OF TRANSDERMAL KETAMINE, FENTANYL, CLONIDINE OR THEIR COMBINATION IN CHRONIC LOW BACK PAIN

Objectives: chronic low back pain may result in central sensitization, with involvement of different receptors. The aim of this study was to evaluate the analgesic action of transdermal (T) ketamine (a NMDA antagonist), clonidine (an α2-agonist), fentanyl (an opioid agonist), or their combination in chronic low back pain. Methods: after the institutional approval and informed consent signature, 54 patients were prospectively randomized into 6 groups. Each patient had two of the T preparations applied in different arms. The effect of either T ketamine (1 mg/h), T clonidine (25 μg/h) or T fentanyl (25 μg/h), combined with T placebo (CloG, KetG and FenG); or the combination of T ketamine and clonidine RESUMO Objetivos: a dor lombar cronica pode resultar em sensibilizacao central, com a participacao de diferentes tipos de receptores. O objetivo deste estudo foi avaliar a acao analgesica por via transdermica (T) do fentanil, cetamina, clonidina ou suas associacoes para o alivio da dor lombar cronica. Metodos: apos aprovacao do Comite de Etica em Pesquisa e assinatura do termo de consentimento livre e esclarecido, 54 pacientes foram avaliados de forma prospectiva, aleatoria e duplamente-encoberta, sendo divididos em 6 grupos. Cada paciente recebeu duas preparacoes por via transdermica, aplicadas em bracos diferentes (T cetamina (1 mg/h), T clonidina (25 μg/h) ou T fentanil (25 μg/h), associados a T placebo (CloG, CetG and RESUMEN Objetivos: el dolor lumbar cronico puede resultar en sensibilizacion central, con la participacion de diferentes tipos de receptores. El objetivo de este estudio fue evaluar la accion analgesica por via transdermica (T) del fentanyl, cetamina, clonidina o sus asociaciones en dolor lumbar cronico. Metodos: despues de la aprobacion por el Comite de Etica en Investigacion y Consentimiento, 54 pacientes fueron evaluados de forma prospectiva, aleatoria e duplamenteciego siendo divididos en seis grupos. Cada paciente recibio dos preparaciones por via transdermica, aplicadas en brazos diferentes (T cetamina (1 mg/h), T clonidina (25 μg/h) o T fentanyl (25 μg/h), asociados a T placebo (CloG, CetG y FenG); o la Study carried out at Clinica para o Tratamento da Dor of the Hospital das Clinicas of the Faculdade de Medicina de Ribeirao Preto of Universidade de Sao Paulo – USP – Ribeirao Preto (SP), Brazil. 1Associate Professor at Faculdade de Medicina de Ribeirao Preto of Universidade de Sao Paulo – USP– Ribeirao Preto (SP), Brazil. 2Postgraduate Student of Orthopedic Area at Faculdade de Medicina de Ribeirao Preto of Universidade de Sao Paulo – USP– Ribeirao Preto (SP), Brazil. 3Assistant Professor at Faculdade de Medicina de Ribeirao Preto of Universidade de Sao Paulo – USP – Ribeirao Preto (SP), Brazil. 4Professor at Faculdade de Ciencias Farmaceuticas de Ribeirao Preto of Universidade de Sao Paulo – USP – Ribeirao Preto (SP), Brazil. 5Assistant Professor at Faculdade de Ciencias Farmaceuticas de Ribeirao Preto of Universidade de Sao Paulo – USP – Ribeirao Preto (SP), Brazil. Recebido: 10/10/2009 Aprovado: 20/11/2009 The clinical and laboratorial evaluation of transdermal ketamine, fentanyl, clonidine or their combination in chronic low back pain COLUNA/COLUMNA. 2009;8(4):434-440 435 (Ket-CloG), T fentanyl and ketamine (Fen-KetG), or T fentanyl and clonidine (Fen-CloG) was searched for pain and adverse effects. Pain was evaluated by: 1) VAS pain scores, and 2) noradrenaline plasma levels at 0-h (just prior to T application), 3and 6-h after the T application of two medications, by HPLC. Results: clinically, the pain VAS score at 6-h was smaller in comparison to the 0-h in all groups (p<0.02), and lower when compared to the Fen-CloG and Fen-KetG at the 6-h in relation to the administration of each correspondent T drug alone (p<0.05). The laboratorial data revealed that administration of T fentanyl alone (FenG) resulted in plasma noradrenaline decrease at 6-h (p<0.01), while the association of T fentanyl with clonidine resulted in plasma noradrenaline decrease at 3and 6-h as compared to the others (p<0.01). The combination of both T ketamine and clonidine (Ket-CloG) did not result in a better analgesic profile and resulted in excessive sedation during the evaluation (p<0.02). Conclusions: all the studied drugs resulted in clinical analgesia (VAS) at 6-h. However, T fentanyl analgesia was corroborated by lower plasma noradrenaline levels at 6-h when applied alone or at 3-h when combined with T clonidine.