Abstract
Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR), as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53). Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.
Highlights
Bone pain is a common and severe symptom in cancer patients, especially in advanced stage (Jimenez-Andrade et al, 2010; Kane, Hoskin & Bennett, 2015; Mantyh, 2014; Mantyh & Hunt, 2004)
The present study aimed to examine the potential application of lappaconitine in leukemia bone pain
The K562 cell transplanted group exhibited spontaneous pain which was began at 7–9 days after injection of K562 cells, lasting for the rest of the experiment; the treatment with lappaconitine at 4 mg/kg on day 15, 17 and 19 reduced the spontaneous pain significantly compared to the untreated K562 group, but did not alleviate the pain completely (Fig. 2, ∗P < 0.05, ∗∗∗P < 0.001, compared with the control groups; ##P < 0.01, ###P < 0.001, compared with the K562 cells group)
Summary
Bone pain is a common and severe symptom in cancer patients, especially in advanced stage (Jimenez-Andrade et al, 2010; Kane, Hoskin & Bennett, 2015; Mantyh, 2014; Mantyh & Hunt, 2004). The available pharmacological tools for bone pain analgesia are limited, with unstable efficacy and sometimes adverse side effects (Kane, Hoskin & Bennett, 2015; Mantyh, 2014). Lappaconitine is one bioactive component isolated from aconitum sinomonatum nakai with clinical efficacy in chronic pain and inflammation (Ono & Satoh, 1988; Ono & Satoh, 1991; Wang et al, 2009; Wright, 2001), which is the most effective drug presently available for the treatment of malignant tumor and other intractable pain (Wang et al, 2009). Using methods for screening of analgesics, the results obtained from Ono and Satoh showed that the analgesic effects of lappaconitine were generally about 2 to 5 times less potent than
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