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Neuropharmacology. 2018 Mar 1;130:18-29. doi: 10.1016/j.neuropharm.2017.11.036. Epub 2017 Nov 27.

Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice.

Author information

1
Washington University Pain Center, St. Louis, MO 63110, USA; Department of Anesthesiology, St. Louis, MO 63110, USA. Electronic address: a.shepherd@wustl.edu.
2
Washington University Pain Center, St. Louis, MO 63110, USA; Department of Anesthesiology, St. Louis, MO 63110, USA; Center for the Investigation of Membrane Excitability Diseases, St. Louis, MO 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: d.p.mohapatra@wustl.edu.

Abstract

The urgent need for more effective analgesic treatment options has prompted a re-evaluation of the behavioral tests used to assess pain in pre-clinical research, with an emphasis on inclusion of more voluntary, un-evoked behavioral assessments of pain. In order to validate voluntary gait analysis and a voluntary mechanical conflict-avoidance assay, we tested mouse models of neuropathy (spared nerve injury) and inflammation (complete Freund's adjuvant) alongside reflexive measures of mechanical and thermal hypersensitivity. To establish whether the observed changes in behavioral responses were pain-related, known analgesics (buprenorphine, gabapentin, carprofen) were also administered. Spared nerve injury persistently altered several gait indices, whereas complete Freund's adjuvant caused only transient changes. Furthermore, known analgesics could not reverse these gait changes, despite demonstrating their previously established efficacy in reflexive measures of mechanical and thermal hypersensitivity. In contrast, the mechanical conflict-avoidance assay demonstrated aversion in mice with neuropathy and inflammation-induced hypersensitivity, which could both be reversed by analgesics. We conclude that voluntary gait changes in rodent neuropathic and inflammatory pain models are not necessarily indicative of pain-related adaptations. On the other hand, mechanical conflict-avoidance represents a valid operant assay for quantifying pain-related behaviors in mice that can be reversed by known analgesics.

KEYWORDS:

Catwalk; Conflict-avoidance; Gait; Inflammatory pain; Neuropathic pain

PMID:
29191755
PMCID:
PMC5743638
DOI:
10.1016/j.neuropharm.2017.11.036
[Indexed for MEDLINE]
Free PMC Article

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