Efficacy of the World Health Organization analgesic ladder in the paclitaxel-induced pain syndrome in rats
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Inflammopharmacology
ORIGINAL ARTICLE
Efficacy of the World Health Organization analgesic ladder in the paclitaxel‑induced pain syndrome in rats Kelly de Vargas Pinheiro1 · Indiara Brusco2 · Bruna dos Santos Hausen3 · Rafael Noal Moresco1,3 · Flávia K. Rigo2,4 · Sara Marchesan Oliveira2 · Juliano Ferreira1,2,5 Received: 28 November 2019 / Accepted: 15 March 2020 © Springer Nature Switzerland AG 2020
Abstract Paclitaxel use in cancer treatment is limited by a painful syndrome that has no effective treatment. Despite new therapies, drugs of the World Health Organization (WHO) analgesic ladder remain a useful therapeutic tool for cancer pain relief. Since cancer pain is caused by both tumor and chemotherapy, we assessed the efficacy of drugs from the WHO analgesic ladder for cancer pain relief in a paclitaxel-induced pain syndrome (P-IPS) model. P-IPS was induced in rats by one or four injections of paclitaxel on alternate days. The acute and chronic phases were assessed 24 h and 15 days after the first paclitaxel injection, respectively. The mechanical allodynia was evaluated after (step 1 of the ladder) paracetamol, (step 2) codeine alone or plus paracetamol and (step 3) morphine treatment in the acute or chronic phase of P-IPS. Paracetamol, codeine and morphine were equally efficacious in reducing the acute phase of the P-IPS. Codeine plus paracetamol had similar efficacy and potency when administered together in the acute phase of the P-IPS, but produced a longer-lasting effect than when separately managed. Moreover, paracetamol, codeine and morphine partially reduced the chronic phase of P-IPS, losing their efficacy and, in the case of codeine, potency when compared to the acute phase. However, paracetamol plus codeine increased the potency and efficacy of the codeine when compared to codeine administered alone in the chronic phase of P-IPS, producing a long-lasting anti-allodynic effect. Together, analgesics of WHO analgesic ladder reduce both acute and chronic phases of P-IPS, with codeine plus paracetamol presenting more potent, efficacious and long-lasting effect. Thus, in addition to tumor pain, drugs of WHO analgesics ladder could also be useful to treat P-IPS. Graphic abstract
Keywords Allodynia · Neoplasms · Opioids · Chemotherapy · Nsaids * Sara Marchesan Oliveira [email protected]; [email protected] * Juliano Ferreira [email protected] Extended author information available on the last page of the article
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Introduction Cancer is an important cause of morbidity and mortality, and it was responsible for 18.1 Mio. new cases and 9.6 Mio. cancer deaths worldwide in 2018 (Bray et al. 2018; WHO 2018). Pain is one of the most important symptoms presented by cancer patients, causing a great impact on their quality of life (Schug, Chandrasena 2015). Cancer pain may be originated from different processes, such as direct infiltration/involvement of the tumor (tumor-induced pain) or even as an adverse effect of the cancer therapy (e.g., chemotherapy-induced pain) (Quasth
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