Antinociceptive Activity of the Skin Secretion of Phyllomedusa rohdei (Amphibia, Anura).

Pain is a distressful experience that can have a major impact on an individual's quality of life. The need for new and better analgesics has been further intensified in light of the current opioid epidemic. Substances obtained from amphibians have been shown to contain bioactive peptides that exert analgesic effects. The genus Phyllomedusa represents an important source of peptides and bioactive components. The aim of this study was to investigate the antinociceptive effects of the skin secretion of Phyllomedusa rohdei in rodent models of pain. The crude skin extract of P. rohdei was tested in different pain models: acetic acid-induced writhing test (mice), formalin test (rats), Von Frey electronic test for hypernociception induced by PGE2 (rats), and hot plate test (mice). Motor-impairing effects were tested using the rota-rod test. The results showed that the skin extract of P. rohdei exerted antinociceptive effects in all pain models tested. Particularly, the highest dose tested of the skin extract decreased acetic acid-induced writhing by 93%, completely blocked formalin-induced nociception both during the acute and inflammatory phases of the test, PGE2-induced hypernociception by 73% and increased latency to paw withdrawal in the hot plate test by 300%. The effects observed in the hot plate test were reversed by pretreatment with selective µ and κ, but not δ, opioid receptor antagonists, indicating a mechanism of action dependent on µ and κ opioid receptors. The results were not influenced by sedative effects. Further studies remain necessary to reveal the specific compounds involved in the antinociceptive effects of P. rohdei skin extract as a new therapeutic tool in pain management.

Ocimum gratissimum Essential Oil and Its Isolated Compounds (Eugenol and Myrcene) Reduce Neuropathic Pain in Mice.

Ocimum gratissimum is used in popular medicine to treat painful diseases. The antihypernociceptive properties of O. gratissimum essential oil and two of its active components (eugenol and myrcene) were tested in a model of neuropathic pain induced by a chronic constriction injury of the sciatic nerve. In tests to determine chronic antinociception, adult male C57BL/6 J mice were treated orally with corn oil (control group), O. gratissimum essential oil at doses of 10, 20, or 40 mg/kg or eugenol or myrcene at doses of 1, 5, or 10 mg/kg for 14 days after surgery. Pregabalin (20 mg/kg) was used as a standard in this study. The treatment with 20 and 40 mg/kg of O. gratissimum essential oil and at doses of 5 and 10 mg/kg of the active components were able to promote antihypernociception in both mechanical (von Frey) and thermal (hot plate) tests. The treatment with the essential oil of the plant or eugenol was effective in reducing the levels of interleukin-1ß in the sciatic nerve. Our findings demonstrate that O. gratissimum essential oil and its isolated active components possess antihypernociceptive activity in neuropathic pain models.

Phyllanthus amarus does not affect hypernociception in experimental autoimmune encephalomyelitis.

Multiple sclerosis is an inflammatory disease of the central nervous system. Chronic pain is one of the main symptoms, affecting many patients. Studies show that the lignans or the apolar extracts of Phyllanthus amarus have antinociceptive effects in different animal models. To evaluate the antihypernociceptive effect of a hexanic extract of P. amarus in experimental autoimmune encephalomyelitis in mice, the chemical composition of the hexanic extract was analyzed by gas chromatography mass spectrometry. After EAE induction, animals were treated with the hexanic extract of P. amarus for 26 consecutive days. Motor coordination and mechanical hypernociception were evaluated on alternate days. The principal lignans found were phyllanthin, niranthin, and 5-demethoxyniranthin. The hexanic extract of P. amarus at a dose of 100, 200, or 400 mg/kg did not affect the development of the disease. The motor coordination and pain threshold of the treated animals were not altered in this experiment. In conclusion, in this test, the hexanic extract of P. amarus did not show evidence of antihypernociceptive activity in experimental autoimmune encephalomyelitis.