Effects of putative chronic pain models on locomotor activity in female and male mice

Behavioral depression is a cardinal sign of clinically relevant pain and a target of pain treatment. Accordingly, preclinical assays of pain-depressed behavior can serve as tools for translational research on the expression and treatment of this key manifestation of pain. We recently validated a procedure to assess expression and pharmacological treatment of acute pain-related depression of locomotor activity produced in mice by acute treatment with intraperitoneal lactic acid (IP acid). The present study evaluated the utility of this procedure for research on locomotor depression produced by four putative models of chronic pain: (1) a model of episodic visceral pain produced by repeated daily IP acid injection, (2) a laparotomy model of postsurgical pain, (3) a cutaneous inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant (Ipl CFA), and (4) a spared nerve injury (SNI) model of neuropathic pain. Locomotor activity in male and female ICR mice was objectively and quantitatively assessed in chambers with two compartments separated by a wire-mesh barrier that could be surmounted to cross between compartments. Primary dependent measures were vertical activity represented by Crosses between compartments and horizontal activity represented by the sum of photobeam breaks (Movement Counts) within each compartment. Repeated IP acid and laparotomy depressed both Crosses and Movement, and effects were alleviated by analgesics. Ipl CFA and SNI produced weak effects too small and variable to permit drug testing. These results support utility of repeated IP acid and laparotomy models for research on pain-related behavioral depression using locomotor endpoints in mice. PERSPECTIVE: Clinically relevant pain commonly produces behavioral depression. This article compared locomotor depression in mice produced by four chronic pain models. Two models (episodic visceral pain, postsurgical pain) produced locomotor depression alleviated by analgesics. Inflammatory and neuropathic pain models produced weak effects that limit their utility for research on pain-depressed behavior.