Stephalagine, an aporphinic alkaloid with therapeutic effects in acute gout arthritis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Gout is an inflammatory disease characterized by the accumulation of monosodium urate crystals (MSU) in the joints, leading to severe pain and inflammation. Stephalagine is a Brazilian Savanna aporphine alkaloid isolated from Annona crassiflora Mart. Fruit peel, that has been popularly used to treat rheumatism and have been described with antinociceptive properties. However, no studies evaluated the possible therapeutic properties of stephalagine in arthritic pain. AIM OF THE STUDY: To evaluate the possible antinociceptive and anti-inflammatory effects of stephalagine in an acute gout attack in mice. MATERIALS AND METHODS: Adult male wild type C57BL/6/J/UFU mice (20-25 g) were used (process number 018/17). The treated group received stephalagine (1 mg/kg, by gavage) and the vehicle group received saline (10 mL/kg, by gavage), both 1 h before the MSU crystals (100 µg/ankle joint) administration. All groups were analyzed for mechanical allodynia, thermal hyperalgesia, overt pain-like behaviors, and edema development at 2, 4, 6 and 24 h after injections. Synovial fluid and the ankle articulation from the injected joint were collected 4 h after administrations for myeloperoxidase enzyme activity, IL-1ß measurement, and histological analysis. RESULTS: Stephalagine had a significant antinociceptive effect on mechanical allodynia, when compared to vehicle group at 2-24 h after intra-articular injection of MSU and 2 h for spontaneous and cold thermal sensitivity. Stephalagine was also able to significantly reduce the articular edema (45 ± 1%), the activity of the myeloperoxidase enzyme (37 ± 6%), and IL-1ß levels (43 ± 3%). The histological analysis confirms that stephalagine dramatically reduced the number of infiltrating inflammatory cells (75 ± 6%) in MSU injected animals. Also, stephalagine treatment did not alter the uric acid levels, xanthine oxidase activity, AST and ALT activities, urea and creatinine levels, neither cause any macroscopic changes in the mice's weight, deformations, changes in the coat, or feces. CONCLUSION: Stephalagine may be an alternative for the management of gout, once it was able to induce antinociceptive and anti-inflammatory effects without causing adverse effects on the evaluated parameters.

Analgesic potential of different available commercial brands of botulinum neurotoxin-A in formalin-induced orofacial pain in mice.

The use of botulinum neurotoxin-A (BoNT-A) is an alternative for the management of orofacial pain disorders. Although only Botox has labeled, there are other commercial brands available for use, among them: Dysport, Botulift, Prosigne, and Xeomin. The objective of the present study was to evaluate the possible differences in the antinociceptive effect evoked by different commercially available formulations of BoNT-A in an animal model of inflammatory orofacial pain induced by formalin injection. Male C57/BL6 mice (20-25 g) were submitted to the pre-treatment with five different commercial brands of BoNT-A (Botox, Botulift, Xeomin, Dysport, or Prosigne; with doses between 0.02 and 0.2 Units of Botulinum Toxin, in 20 µL of 0.9% saline) three days prior the 2% formalin injection. All injections were made subcutaneously into the right perinasal area. After formalin injections, nociceptive behaviors like rubbing the place of injection were quantified during the neurogenic (0-5 min) and inflammatory (15-30 min) phases. The treatment using Botox, Botulift, and Xeomin were able to induce antinociceptive effects in both phases of the formalin-induced pain animal model, however, Dysport and Prosigne reduced the response in neither of them. Our data suggest that the treatment using different formulations of BoNT-A is not similar in efficacy as analgesics when evaluated in formalin-induced orofacial pain in mice.