The clinical and laboratorial evaluation of transdermal ketamine, fentanyl, clonidine or their combination in chronic low back pain

Abstract

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 (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), 3- and 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 3- and 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.