Evaluation of the efficacy of intrathecal injection of amitriptyline and doxepin in spinal anesthesia in comparison with bupivacaine in rats

BACKGROUND: Tricyclic antidepressants (TCAs) are commonly used orally for treating chronic pain states, such as neuropathic pain. TCAs produce analgesia by various mechanisms, including sodium channels, N-methyl-d-aspartate receptors, biogenic amines, opioids, inflammatory mediators, and substance P. Studies have shown that intrathecal tricyclic administration effectively attenuates pain and thermal hyperalgesia in inflammatory and neuropathic pain in rats. OBJECTIVES: The aim of this study was to evaluate the effect of two tertiary TCAs in sensory and motor block. We also used bupivacaine as a strong local anesthetic for the control group. MATERIALS AND METHODS: In a double-blind randomized controlled trial in an animal lab, intrathecal injection of drugs was performed in 30 Wistar male rats. We divided the subjects into 3 groups: group 1: 90 µL Doxepine (50 mM), group 2: 90 µl amitriptyline (60 mM). and group 3: 90 µL bupivacaine (23 mM). Then sensory, motor, and proprioceptive changes were measured at 1, 2, 3, 4, 6, and 12 hours by one examiner. RESULTS: In Groups 1 and 2, a total of 3 rats died. After adjusting the concentrations, amitriptyline had a similar potency but a longer duration of spinal blockade of motor, proprioception, and nociception than did bupivacaine (p < 0.05), whereas doxepin had a reasonable but lower efficacy and shorter duration of spinal blockade than did bupivacaine (p < 0.05). The full recovery time for Group 2 was significantly longer. CONCLUSIONS: It seems that tertiary amine drugs such as amitriptyline and doxepin had reasonable potencies of spinal blockade when compared to bupivacaine. However, amitriptyline had a more potent and long-acting spinal anesthetic effect. Amitriptyline may turn out to be a clinically valuable local anesthetic.