Open AccessSpider peptide Phα1β induces analgesic effect in a model of cancer pain
Author(s) -
Rigo Flavia Karine,
Trevisan Gabriela,
Rosa Fernanda,
Dalmolin Gerusa D.,
Otuki Michel Fleith,
Cueto Ana Paula,
Castro Junior Célio José,
RomanoSilva Marco Aurelio,
Cordeiro Marta do N.,
Richardson Michael,
Ferreira Juliano,
Gomez Marcus V.
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12209
Subject(s) - morphine , analgesic , cancer pain , medicine , adverse effect , pharmacology , cancer , neuropathic pain , nociception , anesthesia , receptor
The marine snail peptide ziconotide (ω‐conotoxin MVIIA ) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side‐effects of spider peptide P hα1β in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B 16‐ F 10 cells into the hind paw of C 57 BL /6 mice. After 14 days, painful hypersensitivity was detected and P hα1β or ω‐conotoxin MVIIA (10–100 pmol/site) was intrathecally injected to evaluate the development of antinociception and side‐effects in control and morphine‐tolerant mice. The treatment with P hα1β or ω‐conotoxin MVIIA fully reversed cancer‐related painful hypersensitivity, with long‐lasting results, at effective doses 50% of 48 (32–72) or 33 (21–53) pmol/site, respectively. Phα1β produced only mild adverse effects, whereas ω‐conotoxin MVIIA induced dose‐related side‐effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol/site). In addition, we observed that P hα1β was capable of controlling cancer‐related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 ± 5% of inhibition). In this study, P hα1β was as efficacious as ω‐conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid‐tolerant mice, indicating that P hα1β has a good profile for the treatment of cancer pain in patients.