Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

Abstract

Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

Lack of efficacy of a partial adenosine A1 receptor agonist in neuropathic pain models in mice

“…3a). By contrast, the positive control pregabalin (60 mg/kg [23,27]), significantly ameliorated the mechanical hypersensitivity, confirming that the SNI-induced neuropathic pain behavior is responsive to standard analgesic treatment. We then investigated whether capadenoson treatment may inhibit chemotherapy-induced neuropathic pain in the paclitaxel model.…”

“…By contrast, pregabalin, which in this experiment was given at 30 mg/kg p.o. [27], significantly inhibited the mechanical hypersensitivity in comparison to vehicle (Fig. 3c).…”

Herbal Medicine for Pain Management: Efficacy and Drug Interactions

“…Several pre-clinical studies have investigated interactions between curcumin and drugs. One such study in mouse models of acute nociceptive pain demonstrated a synergistic interaction in combination with pregabalin [ 61 ]. Curcumin was found to downregulate opioid-related nociceptin receptor 1 gene expression, which codes for nociceptin opioid peptide receptor (NOP), one of the four opioid receptors.…”

Synthesis, in vivo and in silico analgesic and anti-inflammatory studies of α-D-ribofuranose derivatives

“…The tail flick method is also broadly applied to assess anti-nociceptive property of compounds. Exposing the tail of mice to heat activates heat sensitive receptors, transient receptor potential vanilloid type 1 and 3 (TRPV1 and TRPV3) receptors promoting pain transmission ( Leksiri et al, 2020 ). Compound 3 exhibited potent analgesic activity in both the tests.…”