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 ...

BackgroundOpioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated.ResultsThe potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.ConclusionThese results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Background and Methods: Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis. Results: Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED₅₀ of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1 ratio of their ED₅₀, had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively. Conclusion: The data showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alternative that can be used for neuropathic pain management.

These results suggest that gabapentin produce antinociception partly via the activation nitridergic pathways and opioid system.

Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.