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.

中文翻译：

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世界卫生组织止痛梯在紫杉醇诱发的大鼠疼痛综合征中的功效。

紫杉醇在癌症治疗中的使用受到无法有效治疗的疼痛综合征的限制。尽管有新疗法，世界卫生组织（WHO）止痛药仍然是缓解癌症疼痛的有用治疗工具。由于癌症疼痛是由肿瘤和化学疗法共同引起的，因此我们在紫杉醇诱发的疼痛综合征（P-IPS）模型中评估了WHO止痛阶梯药物缓解癌症疼痛的功效。在隔日通过一或四次紫杉醇注射在大鼠中诱导P-IPS。第一次紫杉醇注射后24小时和15天分别评估急性期和慢性期。在P-IPS的急性或慢性阶段（阶梯的第1步）对乙酰氨基酚，（第2步）可待因单独或加对乙酰氨基酚和（第3步）吗啡治疗后评估机械性异常性疼痛。扑热息痛，可待因和吗啡在减少P-IPS急性期方面同样有效。可待因加扑热息痛在P-IPS急性期一起给药时具有相似的功效和效力，但与单独给药时相比，效果更持久。此外，扑热息痛，可待因和吗啡可部分减轻P-IPS的慢性期，与急性期相比，会降低其功效，并且在可待因的情况下会降低药效。但是，与在P-IPS慢性期单独给药的可待因相比，扑热息痛加可待因提高了可待因的效力和功效，产生了持久的抗痛觉过敏作用。一起，WHO止痛梯的止痛药可减少P-IPS的急性期和慢性期，可待因加对乙酰氨基酚的作用更强，更有效且更持久。从而，