Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats

Abstract

Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.

Sigma‐1 receptor antagonist (BD‐1063) potentiates the antinociceptive effect of quercetin in neuropathic pain induced by chronic constriction injury

“…The evidence is related to the use of traditional drugs for the treatment of this type of pain such as gabapentinoids in combination with opioid drugs, such as morphine, oxycodone and tapentadol, or with antidepressants, such as duloxetine, as well as the combination of antidepressants with opioid drugs (Chaparro, et al, 2012; Christoph, De Vry, Schiene, Tallarida, & Tzschentke, 2011; De la O‐Arciniega et al, 2009; García‐Martínez et al, 2016). Some studies have used NSAIDs with antiepileptic or opioid drugs that showed promising results at the preclinical level (Abass, Mosbah, Rizk, Karrouf, & Zaghloul, 2014; Espinosa‐Juárez, Jaramillo‐Morales, Corona‐Ramos, Medina‐López, & López‐Muñoz, 2016). All these combinations tend to induce additive or synergistic effects; however, in these works, it was not possible to determine which combinations could produce the best effect.…”

Synergistic Interaction of a Gabapentin‐ Mangiferin Combination in Formalin‐Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO‐Cyclic GMP‐ATP‐Sensitive K+ Channel Pathway

“…Gabapentin injected intradermally into the hindpaw can induce analgesia [Todorovic et al, ] and gabapentin is also effective in acute and chronic models of inflammatory pain [Singh et al, ; Heughan and Sawynok et al, ; Hurley et al, ] and reverses allodynia and hyperalgesia induced by 1% formalin [Salinas‐Abarca et al, ]. Gabapentin can decrease allodynia induced by nerve lesions in a neuropathic rat model [Chen et al, ; Field et al, ; Mixcoatl‐Zecuatl et al, ; Yamama et al, ; Miranda et al, ; Corona‐Ramos et al, ; Espinosa‐Juárez et al, ]. The antiallodynic effect of gabapentin may result from binding to the α2δ1 subunit of L‐type voltage‐dependent Ca 2+ channels [Gee et al, ] although it could activate other targets.…”

“…For our knowledge, this study shows for the first time the synergistic interaction of these two drugs. However, gabapentin has been co‐administered with (1) NSAIDs like naproxen [Hurley et al, ], meloxicam [Espinosa‐Juárez et al, ], ibuprofen [Yoon and Yaksh, ], diclofenac [Picazo et al, ] and metamizol [Ortega‐Varela et al, ]. (2) antidepressants like venlafaxine [Rode et al, ], nortriptyline [Miranda et al, ], and amitriptyline [Heughan and Sawynok, ].…”

The positive and negative effects of using transdermal nonsteroidal anti-inflammatory drugs: chemoreactome analysis

“…5, в). В эксперименте было показано, что мелоксикам усиливал анальгетический эффект агониста ГАМК-рецепторов габапентина у крыс с моделью невропатической боли [19]. Заключение.…”