Abstract

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.

Highlights

  • Pain is a major global public health problem

  • Animals treated with the lowest dose (0.3 mg/kg) of skin extract of Phyllomedusa rohdei (SEPr) extract showed no significant differences compared to the control acetic acid group

  • Animals treated with the lowest dose (0.3 mg/kg) of SEPr extract doses of a skin extract of Phyllomedusa rohdei (SEPr) on the acute or inflammatory phases of the showed no significant compared to the control acetic produce acid group

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Summary

Introduction

According to the World Health Organization (WHO), one in every five adults frequently experience pain, and one in every ten adults, or 30% of the world. Toxins 2020, 12, 589 population, is diagnosed with chronic pain each year [1,2]. Inflammation is one of the main features associated with chronic pain. Pain and inflammation are regulated by a bidirectional interaction between nociceptor sensory neurons and immune cells, which contributes to pathology in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, asthmatic lung disease, and colitis [4]. The available therapeutic options for chronic pain, including opioids, are associated with a high number of adverse reactions, tolerance and dependence [5]. In light of the current opioid epidemic, new research on treatment alternatives for chronic pain remains necessary

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