Abstract
A primary goal in pain treatment is restoration of behaviors that are disrupted by pain. Measures of pain interference indicate the degree to which pain interferes with activities in pain patients, and these measures are used to evaluate the effects of analgesic drugs. As a result of the emphasis on the expression and treatment of functional impairment in clinical settings, preclinical pain researchers have attempted to develop procedures for evaluation of pain-related functional impairment in laboratory animals. The goal of the present study was to develop and validate a low cost procedure for the objective evaluation of pain-related depression of home cage behavior in mice. On test days, a 5 × 5 cm Nestlet was weighed prior to being suspended from the wire lid of the home cage of individually housed male and female ICR mice. Over the course of experimental sessions, mice removed pieces of the suspended Nestlet, and began to build a nest with the material they removed. Thus, the weight of the pieces of Nestlet that remained suspended at various time points in the session provided an indicator of the rate of this behavior. The results indicate that Nestlet shredding was stable with repeated testing, and shredding was depressed by intra-peritoneal injection of 0.32% lactic acid. The non-steroidal anti-inflammatory drug ketoprofen blocked 0.32% lactic acid-induced depression of shredding, but did not block depression of shredding by a pharmacological stimulus, the kappa opioid receptor agonist U69,593. The μ-opioid receptor agonist morphine did not block 0.32% lactic acid-induced depression of shredding when tested up to doses that depressed shredding in the absence of lactic acid. When noxious stimulus intensity was reduced by decreasing the lactic acid concentration to 0.18%, morphine was effective at blocking pain-related depression of behavior. In summary, the data from the present study support consideration of the Nestlet shredding procedure for use in studies examining mechanisms, expression, and treatment of pain-related functional impairment.
Highlights
Pain remains a significant public health issue with some estimates suggesting that close to 40% of adults experience some sort of chronic pain condition [1]
One-way analysis of variance (ANOVA) indicates that lactic acid produced concentration-dependent depression of shredding [F(2.240,24.64) = 19.88; p < 0.05], and Dunnett’s multiple comparison’s test indicates shredding is significantly depressed by 0.18 and 0.32% compared to lactic acid vehicle
The 0.32% concentration of lactic acid was selected for use in drug experiments based on the robust depression of shredding produced by this stimulus
Summary
Pain remains a significant public health issue with some estimates suggesting that close to 40% of adults experience some sort of chronic pain condition [1]. Attempts to mimic clinically relevant pain states (e.g., neuropathic pain, inflammatory pain, disease state) in clinically relevant anatomical features in preclinical models is one example of clinical phenomena informing basic research This example reflects usage of the phrase “pain model” where emphasis is placed on the variables associated with the pain state [4]. An alternative but complementary approach to using clinical phenomena to inform basic science, is the use of models of pain-related functional impairment [5] This approach reflects an acknowledgment of the importance of the dependent variable or target behavior that is used, and the potential value of “modeling” clinically relevant consequences of pain including disruption of behavior
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
