Abstract
Cancer-induced bone pain (CIBP) is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS) in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100mg/kg) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200mg/kg) significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord.
Highlights
Cancer-induced bone pain (CIBP) is a frequent complication in patients suffering from bone metastases [1,2]
Given that the mechanical allodynia in CIBP rats could be substantially alleviated by a non-specific Reactive oxygen species (ROS) scavenger, we examined the analgesic effect of a superoxide selective scavenger Tempol
We demonstrated that (1) i.p. injection of a non-specific ROS scavenger PBN reversed the established mechanical allodynia in CIBP rats, (2) i.p. injection of a superoxide selective scavenger Tempol suppressed the established mechanical allodynia in CIBP rats, (3) repeated injection of PBN and Tempol produced cumulative analgesic effect on CIBP without tolerance, (4) early treatment with PBN
Summary
Cancer-induced bone pain (CIBP) is a frequent complication in patients suffering from bone metastases [1,2]. The World Health Organization (WHO) analgesic ladder remains the golden standard for the management of CIBP in clinic [3,4]. The production of ROS is tightly regulated by antioxidant defense systems [9]. Excessive ROS levels due to increased ROS production and/or decreased antioxidant defense ability leads to lipid peroxidation, protein oxidation, and nucleic acid oxidation [10]. Emerging evidence suggested that ROS scavengers showed potent analgesic effect in rodent models of inflammatory pain and neuropathic pain [11,12,13,14]. The present study examined the antinociceptive effect of two ROS scavengers in a well-established CIBP model
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