title: Neuropathic changes in equine laminitis pain.
abstract: Laminitis is a common debilitating disease in horses that involves painful disruption of the lamellar dermo-epidermal junction within the hoof. This condition is often refractory to conventional anti-inflammatory analgesia and results in unremitting pain, which in severe cases requires euthanasia. The mechanisms underlying pain in laminitis were investigated using quantification of behavioural pain indicators in conjunction with histological studies of peripheral nerves innervating the hoof. Laminitic horses displayed consistently altered or abnormal behaviours such as increased forelimb lifting and an increased proportion of time spent at the back of the box compared to normal horses. Electron micrographic analysis of the digital nerve of laminitic horses showed peripheral nerve morphology to be abnormal, as well as having reduced numbers of unmyelinated (43.2%) and myelinated fibers (34.6%) compared to normal horses. Sensory nerve cell bodies innervating the hoof, in cervical, C8 dorsal root ganglia (DRG), showed an upregulated expression of the neuronal injury marker, activating transcription factor-3 (ATF3) in both large NF-200-immunopositive neurons and small neurons that were either peripherin- or IB4-positive. A significantly increased expression of neuropeptide Y (NPY) was also observed in myelinated afferent neurons. These changes are similar to those reported in other neuropathic pain states and were not observed in the C4 DRG of laminitic horses, which is not associated with innervation of the forelimb. This study provides novel evidence for a neuropathic component to the chronic pain state associated with equine laminitis, indicating that anti-neuropathic analgesic treatment may well have a role in the management of this condition.
authors.affiliation: Centre for Neuroscience Research, Division of Veterinary Biomedical Sciences, R(D)SVS, The University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, United Kingdom Division of Veterinary Clinical Sciences, R(D)SVS, The University of Edinburgh, Roslin, Midlothian EH25 9RG, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.forename: Ignacio
authors.initials: I
authors.lastname: Viñuela-Fernandez
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Eager
authors.forename: Ada
authors.initials: A
authors.lastname: Delaney
authors.forename: Heather
authors.initials: H
authors.lastname: Anderson
authors.forename: Anisha
authors.initials: A
authors.lastname: Patel
authors.forename: Darren C
authors.initials: DC
authors.lastname: Robertson
authors.forename: Andrew
authors.initials: A
authors.lastname: Allchorne
authors.forename: Eva C
authors.initials: EC
authors.lastname: Sirinathsinghji
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: Milne
authors.forename: Neil
authors.initials: N
authors.lastname: MacIntyre
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Shaw
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Waran
authors.forename: Joe
authors.initials: J
authors.lastname: Mayhew
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fleetwood-Walker
mesh_terms: D000818:Animals; D005260:Female; D005534:Foot Diseases / Q000473:pathology* / Q000662:veterinary*; D006724:Hoof and Claw / Q000473:pathology*; D006734:Horse Diseases / Q000473:pathology*; D006736:Horses; D008297:Male; D009437:Neuralgia / Q000473:pathology* / Q000662:veterinary*; D010146:Pain / Q000473:pathology / Q000662:veterinary; D010147:Pain Measurement / Q000662:veterinary; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000662:veterinary