Abstract
The failure to develop analgesic drugs is attributed not only to the complex and diverse pathophysiology of pain in humans but also to the poor experimental design and poor preclinical assessment of pain. Although considerable efforts have been devoted to overcoming the relevant problems, many features of the behavioral pain assessment remain to be characterized. For example, a decreased locomotor activity as a common presentation of pain-like behavior has yet to be described. Studies on mice experimentally induced with carrageenan have provided opportunities to explore pain-related behaviors in automated home-cage monitoring. Through this approach, the locomotor activities of mice with carrageenan-induced inflammatory pain can be precisely and objectively captured. Here, we found that the mobile behaviors of mice reduced, and their immobility increased, indicating that carrageenan induction in mice caused a significant decrease in locomotor activity. These non-reflexive pain behaviors were strongly correlated with the reflexive pain behaviors measured via von Frey and plantar tests. Furthermore, the pharmacological intervention using indomethacin improved the locomotor activity of mice with carrageenan-induced pain. Thus, the analysis of the locomotor activity in automated home-cage monitoring is useful for studying the behavioral analgesia and the pharmacological screening of analgesic drugs. The combined evaluation of reflexive and non-reflexive pain behaviors enhances the translational utility of preclinical pain research in rodents.
Highlights
The failure to develop analgesic drugs is attributed to the complex and diverse pathophysiology of pain in humans and to the poor experimental design and poor preclinical assessment of pain
The treatment with indomethacin reversed the locomotive impairment induced by carrageenan to the same level as the control group (Fig. 4). These results indicated that indomethacin could effectively enhance the exploratory behaviors impaired by carrageenan administration in LABORAS automated home-cage monitoring
This study revealed that the impairment of long-term locomotor activity of the carrageenan-treated group observed at nighttime significantly differed from that of the control group and this impairment could be improved by indomethacin (Fig. 8)
Summary
The failure to develop analgesic drugs is attributed to the complex and diverse pathophysiology of pain in humans and to the poor experimental design and poor preclinical assessment of pain. One of the non-evoked pain measures, has been utilized as an indicator of behavioral analgesia in numerous pain models, such as complete Freund’s adjuvant (CFA)-induced arthritis[16], postoperative pain[17], spinal cord injury18,19, pruritus[20], streptozotocin-induced diabetic neuropathy, and carrageenan-induced acute inflammatory p ain[21,22]. In these animal models of pain, locomotor activity is improved by the administration of standard analgesic drugs. Clinical studies have demonstrated the correlation of improved physical disability with the improved well-being and quality of life of patients experiencing p ain[25]
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