title: Abnormal gait, due to inflammation but not nerve injury, reflects enhanced nociception in preclinical pain models.
abstract: Validation of gait analysis has the potential to bridge the gap between data from animal pain models and clinical observations. The goal of these studies was to compare alterations in gait due to inflammation or nerve injury to traditional pain measurements in animals. Pharmacological experiments determined whether gait alterations were related to enhanced nociception, edema, or motor nerve dysfunction. Gait was analyzed using an automated system (DigiGait) after injection of an inflammatory agent (carrageenan; CARR or FCA; Freund's complete adjuvant) or nerve injury (axotomy; AXO, partial sciatic nerve ligation; PSNL, spinal nerve ligation; SNL or chronic constriction injury; CCI). All models caused significant alterations in gait and thermal (inflammatory) or mechanical (nerve injury) hyperalgesia. Both indomethacin and morphine were able to block or reverse thermal hyperalgesia and normalize gait in the CARR model. Indomethacin partially blocked and did not reverse paw edema, suggesting that gait alterations must be primarily driven by enhanced nociception. In nerve injury models, AXO, PSNL, CCI, and SNL caused changes to the largest number of gait indices with the rank order being AXO>PSNL=CCI >> SNL. Gabapentin and duloxetine reversed mechanical hyperalgesia but did not normalize gait in any nerve injury model. Collectively, these data suggest that pain is the primary driver of abnormal gait in models of inflammatory but not nerve injury-related pain and suggests that, in the latter, disruption in gait is due to perturbation to the motor system. Gait may therefore constitute an alternative and potentially clinically relevant measure of pain due to inflammation.
authors: Wyeth Research, Neuroscience Discovery Research, CN 8000, Princeton, NJ 08543, USA. pieslam@wyeth.com
authors: Michael J
authors: MJ
authors: Piesla
authors: Liza
authors: L
authors: Leventhal
authors: Brian W
authors: BW
authors: Strassle
authors: James E
authors: JE
authors: Harrison
authors: Terri A
authors: TA
authors: Cummons
authors: Peimin
authors: P
authors: Lu
authors: Garth T
authors: GT
authors: Whiteside
mesh_terms: D000588:Amines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D019771:Axotomy; D002351:Carrageenan; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D000068736:Duloxetine Hydrochloride; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D005620:Freund's Adjuvant; D000077206:Gabapentin; D005684:Gait / Q000187:drug effects* / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009437:Neuralgia / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology; D013876:Thiophenes / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003509:Cyclohexanecarboxylic Acids; D013876:Thiophenes; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D002351:Carrageenan; D005620:Freund's Adjuvant; D000068736:Duloxetine Hydrochloride; D007213:Indomethacin