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.

UK Purine Club 2010 Abstracts

“…UTP and AP 3 A inhibit glucagon-stimulated cyclic AMP levels; 5. glucagon inhibition of EGF-stimulated cell cycle progression is abolished by UTP. These results are consistent with a dominant role for P2Y 1 Fluorescently-labeled ligands, in conjunction with advanced microscopy and spectroscopy, enable the study of pharmacology at the single-cell level. However, engineering a combination of the required pharmacological, photophysical and physicochemical properties of the ligand can be problematic.…”

“…The PCR products were sequenced and compared against predicted sequences. The presence of P2X [1][2][3] receptor subtypes in a variety of equine tissues including dorsal root ganglion and palmar digital nerve was confirmed by Western blot analysis using appropriate validated anti-P2X antibodies. Finally, the presence of P2X 2 and P2X 3 receptor in nervous tissue was confirmed by immunohistochemistry on equine dorsal root ganglion sections.These data provide evidence for the presence of P2X receptors in equine tissue and for the first time, expression of P2X 1-3 receptors in equine nervous tissue.…”

“…Identification of P2X [1][2][3] Laminitis is a condition of horses characterized by disruption of the dermo-epidermal laminar bond within the equine hoof and can result in chronic unremitting pain. The chronic pain state associated with laminitis has been demonstrated to have a neuropathic component 1 .…”

“…This suggests either that the donor molecule itself is a specific antagonist of P2X 4 receptors, or that the lipophilic donor is able to cross the plasma membrane more effectively than CO gas, and act on the inside of the cell. The effects of the CO donor on both P2X 2 and P2X 4 receptors were unaffected by application of 1 H- [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase. The effects of the CO donor were not mimicked by the application of 8-Br-cGMP or mitochondrial transport inhibitors such as potassium cyanide, suggesting no involvement by these signalling pathways.…”

Neuropathic Pain Management in Chronic Laminitis

“…23 It is during the early chronic or active chronic phase of the disease process that relenting pain may develop which often is very difficult to control with traditional antiinflammatory and analgesic drug treatment. 24 However, some animals may pass the early chronic phase rather rapidly without showing severe symptoms and enter the stage of chronic stable laminitis. At this stage they may not display any significant lameness allowing even athletic performance despite unequivocal radiographic evidence of displacement of the distal phalanx.…”