Assessing the long-term consequences for pain in tail amputated pigs: A cautionary tail?

Description

Tail amputation by tail docking or as a consequence of tail biting in pig production systems has serious implications for animal welfare, has been implicated in peripheral nerve injury and may result in chronic pain. The current study, part of the ‘FareWellDock’ project investigating the long-term consequences of pain in tail amputated pigs, provides new evidence to support this. Histopathological analysis of tail stumps collected 1, 4, 8 and 16 weeks after tail docking revealed widespread development of traumatic neuromas from 4 weeks after amputation injury. Traumatic neuromas are often associated with residual stump and phantom limb pain, both recognised as neuropathic pain states. Neuronal dispersion and proliferation within a granulation tissue bed was observed 16 weeks after amputation, in conjunction with epidermal re-innervation. Mechanical nociceptive thresholds were quantified in pigs with intact, 1/3rd and 2/3rds tail amputation pigs at 8 weeks. Significant decreases in tail sensitivity thresholds were observed in both tail amputated groups, 1 and 16 weeks post-amputation (p<0.05). Transcriptome analysis was performed on dorsal root ganglia (DRG) from 2/3rds tail amputated and sham-treated pigs 1, 8 and 16 weeks following amputation at either 3 or 63 days of age. Amputation induced significant changes in gene expression (up and down) compared to sham-treated intact controls for both treatment ages and all time points after tail treatment (p<0.05). Sustained changes in gene expression in tail-amputated pigs were evident four months after tail injury. Correlation network analysis revealed two gene clusters associated with tail amputation: Cluster A (759 down-regulated) and Cluster B (273 up-regulated) genes. Gene ontology analysis identified 124 genes in Cluster A and 61 genes in Cluster B associated with both ‘inflammatory pain’ and ‘neuropathic pain’. In Cluster A, ion channel gene family members, e.g. voltage-gated potassium channels, and receptors, e.g. GABA receptors, were significantly down-regulated compared to shams, both of which are linked to increased peripheral nerve excitability after axotomy. Up-regulated gene families in Cluster B were linked to transcriptional regulation, inflammation, tissue remodelling and regulatory neuropeptide activity. These transcriptomic findings, coupled with observations of long-term reductions in tail stump mechanical nociceptive thresholds, support the suggestion that tail amputation causes sustained changes in peripheral nerve DRG neuron and glial cell function involving key mediators of inflammation and neuropathic pain, which might cause long-term stump pain in pigs.

Period	25 Sep 2019
Event title	Laboratory Animal Science Association (LASA) 3Rs Section/UFAW Meeting: Pain assessment and control
Event type	Workshop
Location	Ware, United Kingdom
Degree of Recognition	National