Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug–drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56–320 mg/kg), antiallodynic (100–562 mg/kg), and antihyperalgesic and anti-inflammatory (10–178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.
Highlights
Pain is the most common symptom by which diseases manifest themselves
nonsteroidal anti-inflammatory drugs (NSAIDs) that are selective cyclooxygenase-2 inhibitors (Coxibs) reduce the incidence of gastrointestinal complications, they have been linked to kidney problems and an increased risk of cardiovascular complications [5,6,7]
The effective dose resulting in a 50% reduction (ED50) in the hyperalgesic response was 101.6 ± 30.9 mg/kg for polyalthic acid and 20.1 ± 4.8 mg/kg for naproxen
Summary
The main function of pain is to protect the integrity of the organism against potentially damaging factors. The same painful stimulus can be perceived in different intensities (mild, moderate, intense) by distinct individuals, depending on psychological, social and cultural factors, among others. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications [3]. NSAIDs can trigger adverse events, such as gastrointestinal ulcers (with consequent bleeding, perforation and/or obstruction), kidney dysfunction, and cardiovascular events, all entailing the risk of death [4]. NSAIDs that are selective cyclooxygenase-2 inhibitors (Coxibs) reduce the incidence of gastrointestinal complications, they have been linked to kidney problems and an increased risk of cardiovascular complications [5,6,7].
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