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Papers of the Week

Papers: 26 Oct 2019 - 1 Nov 2019

Animal Studies, Pharmacology/Drug Development

2020 Mar

Naunyn Schmiedebergs Arch Pharmacol



Antinociceptive and genotoxic assessments of the antagonist TRPV1 receptor SB-366791 on morphine-induced tolerance in mice.


Mazeto T K, Picada J N, Correa Á P, Rebelo I N, Ribeiro M T, Gomez M V, de Souza A H
Naunyn Schmiedebergs Arch Pharmacol. 2020 Mar; 393(3):481-490.
PMID: 31655852.


Chronic pain is mainly treated with opioid analgesics such as morphine. However, the use of these substances can cause adverse effects, including dependence and tolerance, necessitating the discovery of a new approach to analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) is linked to thermal sensibility and has been considered as a new therapeutic option for pain treatment. This study aims to investigate the antinociceptive effect and toxicity of SB-366791, a TRPV1 antagonist. Morphine-tolerant and morphine non-tolerant Swiss mice were submitted to the hot plate and thermal tail flick tests. Toxicological evaluations of the genotoxic and mutagenic activities of SB-366791 were assessed using a comet assay and micronucleus test, and the Salmonella/microsome mutagenicity assay. In the hot plate test, intrathecal injection of SB-366791 or morphine resulted in significantly increased antinociception in non-tolerant mice. SB-366791 also led to an analgesic effect in the tail flick test. Tolerant mice that received SB-366791 demonstrated a central antinociceptive effect in both thermal tests. No genotoxic effects were observed in the comet assay and no mutagenic effects were detected in the micronucleus test or in the Salmonella/microsome assay. Behavioral results of the thermal nociception tests show that SB-366791 has antinociceptive potential in both morphine-tolerant and non-tolerant mice and does not cause genotoxic or mutagenic effects. Nevertheless, new studies should be performed to clarify the activity and participation of vanilloid channels in the antinociception of SB-366791.