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Efficacy of the World Health Organization analgesic ladder in the paclitaxel-induced pain syndrome in rats

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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.

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Acknowledgements

This study was supported by the Conselho Nacional de Desenvolvimento Científico (CNPq; Brasília, Distrito Federal, Brazil) and the Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES; Brasília, Distrito Federal, Brazil). SMO is a recipient of a fellowship from CNPq [process #307220/2017-6]. IB is recipient of fellowship from CAPES/PROEX [process #88882.182148/2018-01]. We also acknowledge the receipt of fellowships from CNPq and CAPES.

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Authors and Affiliations

  1. Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Kelly de Vargas Pinheiro, Rafael Noal Moresco & Juliano Ferreira

  2. Graduate Program in Biological Sciences: Biochemistry Toxicology, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Camobi, Santa Maria, 97105-900, RS, Brazil

    Indiara Brusco, Sara Marchesan Oliveira & Juliano Ferreira

  3. Graduate Program in Pharmaceutics Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Bruna dos Santos Hausen & Rafael Noal Moresco

  4. Graduate Program in Health Sciences, University of Extrem South Catarina, Criciuma, SC, Brazil

    Flávia K. Rigo

  5. Graduate Program in Pharmacology, Department of Pharmacology, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, Trindade, Florianópolis, 88040-900, SC, Brazil

    Juliano Ferreira

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  1. Kelly de Vargas Pinheiro
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Pinheiro, K.V., Brusco, I., Hausen, B.S. et al. Efficacy of the World Health Organization analgesic ladder in the paclitaxel-induced pain syndrome in rats. Inflammopharmacol 28, 1677–1689 (2020). https://doi.org/10.1007/s10787-020-00702-w

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