Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · May 2013
Optimization and characterization of a rat model of prostate cancer-induced bone pain using behavioral, pharmacological, radiological, histological and immunohistochemical methods.
The major limitation of currently utilized rodent models of prostate cancer (PCa)-induced bone pain (PCIBP) involving intra-osseous injection of PCa cells, is their relatively short-term applicability due to progressive deterioration of animal health necessitating euthanasia. Here, we describe establishment of an optimized rat model of PCIBP where good animal health was maintained for at least 90-days following unilateral intra-tibial injection (ITI) of PCa cells. We have characterized this model using behavioral, pharmacological, radiological, histological and immunohistochemical methods. ⋯ Importantly, the histological and radiological assessments confirmed that tumor formation and development of osteosclerotic metastases was confined to the APCC-injected tibial bones. In our rat model of PCIBP, single bolus doses of morphine, gabapentin, meloxicam and amitriptyline produced dose-dependent relief of mechanical allodynia and thermal hyperalgesia in the bilateral hindpaws. The optimized rat model of PCIBP characterized herein has potential to provide new insights into the pathophysiological mechanisms associated with long-term (mal)adaptive pain due to advanced PCa-induced bony metastases and for screening novel compounds with potential for improved alleviation of this condition.