Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain

Abstract

Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1b concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1b induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1b. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1b, in a model of mice PSNL which could be due to an inhibition of glial function.Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system and is characterized by dysaesthesia (an unpleasant abnormal sensation), hyperalgesia (an increased response to painful stimuli) and allodynia (pain in response to a stimulus that does not normally provoke pain) [1]. Different animal models have been developed to model various types of nerve injury, such as spinal cord injury, excitotoxic models, sciatic nerve (neuroma model), sciatic nerve chronic constriction injury, sciatic nerve chronic constriction injury, spinal nerve ligation, polyethylene cuff, partial saphenous nerve injury in mouse, mouse model of trigeminal neuralgia, injection of TNF-a, multiple sclerosis, post-herpetic peripheral neuropathic pain model, HIV-associated sensory neuropathy, diabetic peripheral neuropathic pain model, vincristine-induced peripheral neuropathy model, paclitaxel (taxol)-induced peripheral neuropathy model and cisplatin-induced peripheral neuropathy [2]. The pharmacotherapy of neuropathic pain includes the following: duloxetine, pregabalin, gabapentin, enacarbil, capsaicin, tramadol, botulinum toxin A, lidocaine oxycodone, venlafaxine, amitriptyline, pentadol, valproate, morphine [3]. Amongst drugs that have been tested in neuropathic pain are tramadol and gabapentin. Tramadol, an atypically opioid, is used globally for the treatment of moderate to moderately severe pain, including neuropathic pain [4,5]. On the other hand, gabapentin was developed as an anticonvulsant agent but is helpful for the treatment of chronic neuropathic pain [6]. In addition, gabapentin is recommended as first-line therapy in clinical neuropathy [3]. Furthermore, either ...

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