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.

Quality of Life in Patients with Lumbosacral Radicular Syndrome and Complete Rehabilitation Program (PRISUM PHSD/1/2022)

“…• Reduced the intensity and quality of pain in patients suffering from chronic neuropathic low back pain and was an efficacious adjuvant of the multimodal approach for treating chronic neuropathic lumbar pain [27].…”

“…It has demonstrated the effectiveness of administering medications containing pyrimidine nucleotides (uridine triphosphate -U.T.P., cytidine monophosphate -C.M.P.) in reducing pain intensity associated with diabetic neuropathy, back pain, cervical pain, and trauma-compressive disorders [27], with neuro regenerative properties in the medium term [28]. The use of uridine and cytidine nucleotides associated with hydroxocobalamin had positive control of the intensity of chronic neuropathic low back pain, with a reduction in the consumption of rescue analgesics, thus improving and enhancing the quality of treatment [27,29], and in reducing the pain and improving the motor activity of the patients with alcoholic polyneuropathy [30].…”

“…in reducing pain intensity associated with diabetic neuropathy, back pain, cervical pain, and trauma-compressive disorders [27], with neuro regenerative properties in the medium term [28]. The use of uridine and cytidine nucleotides associated with hydroxocobalamin had positive control of the intensity of chronic neuropathic low back pain, with a reduction in the consumption of rescue analgesics, thus improving and enhancing the quality of treatment [27,29], and in reducing the pain and improving the motor activity of the patients with alcoholic polyneuropathy [30]. Another combination -uridine monophosphate, folic acid, and hydroxycobalamin has been controlled in pain for patients with peripheral neuropathy and neuropathic pain and reduced the adjunctive use of analgesic or anti-inflammatory drugs [31].…”

Transdermal Ketamine and S(+)-Ketamine as Adjuvants Following Orthopaedic Surgery under Bupivacaine Spinal Anaesthesia

“…The analgesic action of transdermal ketamine or S(+)-ketamine analgesia could be due to a central effect, a peripheral effect [20][21][22] or both, secondary to its plasmatic absorption [1,[7][8][9][10][11]. Studies in volunteers described the isomer S(+)-ketamine as a potent analgesic at already low plasma concentrations [23], even at sub anaesthetic plasmatic doses [24].…”

“…As an example, the topical application of a compounded amitriptyline-ketamine formulation improved pain in 75% of patients suffering from erythromelalgia [6] and the use of topical 10% ketamine, might be a useful tool for the treatment of Hidradenitis Supprurativa pain [7]. Proposed mechanisms of ketamine´s analgesia are controversial and include blockade of N-methyl-D-aspartate receptors in a non-competitive fashion [7], analgesia secondary to the absorption of topical ketamine into circulation [1,[8][9][10][11][12], resulting in attenuation of central sensitization [10], or peripheral mechanism of action [13] at cutaneous nociceptors [14].…”