Deficit in voluntary wheel running in chronic inflammatory and neuropathic pain models in mice: Impact of sex and genotype

Behav Brain Res. 2021 Feb 5:399:113009. doi: 10.1016/j.bbr.2020.113009. Epub 2020 Nov 9.


Patients with chronic pain report decreased general activity and emotional distress. Therefore, the development of various animal models that encompass different aspects of pain are crucial for the discovery of genetic differences and the assessment of novel analgesics to improve quality of life. C57BL/6J and DBA/2J mice received unilateral intraplantar injections of 100 % CFA, paclitaxel, or CCI surgery to compare their distance traveled in a voluntary wheel running assay, paw edema diameter, and mechanical sensitivity. Mechanical withdrawal thresholds were lower in both strains of mice that received CFA when compared to their vehicle. However, a decrease in distance traveled was observed in CFA-treated C57BL/6J but not DBA/2J mice. In a separate group, chemotherapy agent paclitaxel 8 mg/kg, i.p. was administered to both strains of mice to induce CIPN which was confirmed by lower mechanical thresholds in paclitaxel-treated mice compared to vehicle-treated mice. Only female C57BL/6J mice showed attenuation of distance traveled following treatment, whereas male C57BL/6J and DBA/2J mice did not. Lastly, C57BL/6J mice underwent chronic constriction injury (CCI) or sham surgery to observe the impact of another chronic neuropathic pain model in wheel running assay. CCI mice showed a gradual decrease in mechanical withdrawal threshold and a decrease in distance traveled compared to sham 5 days following the procedure. Comparing these chronic inflammatory and neuropathic pain models in different mouse strains may help us better understand genetic differences underlying pain perception and its impact on reflexive and nonreflexive outcome measures.

Keywords: CFA; Inflammatory pain; Neuropathic pain; Paclitaxel; Wheel running.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Chronic Pain
  • Disease Models, Animal*
  • Female
  • Freund's Adjuvant / administration & dosage
  • Genotype
  • Hyperalgesia / physiopathology*
  • Inflammation / chemically induced
  • Inflammation / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Motor Activity / physiology*
  • Neuralgia / physiopathology*
  • Nociceptive Pain / chemically induced
  • Nociceptive Pain / physiopathology*
  • Paclitaxel / administration & dosage
  • Peripheral Nerve Injuries / etiology
  • Peripheral Nerve Injuries / physiopathology*
  • Running
  • Sex Factors


  • Adjuvants, Immunologic
  • Antineoplastic Agents, Phytogenic
  • Freund's Adjuvant
  • Paclitaxel