Traumatic neuroma development in tail docked piglets is not associated with long-term changes in spinal nociceptive processing

Concerns exist over the long term consequences for tail stump pain experienced by piglets after docking, especially in relation to traumatic neuroma development in caudal nerves after docking injury. Neuroma formation may cause detrimental sensory changes in the tail due to altered axonal excitability leading to abnormal sensation or pain. The aims of this study were to characterize pig tail histopathology at time intervals up to 16 weeks after tail docking and to measure expression of key neuropeptides in caudal dorsal root ganglia and spinal cord neurons associated with (i) peripheral nerve regeneration; activating transcription factor-3 (ATF3), (ii) inflammatory pain; Calcitonin gene-related peptide (CGRP) and (iii) the maintenance of chronic pain; N-methyl D-aspartate (NMDA) ionotropic glutamate receptor subtype 2B (GRIN2B) at the same time points after tail docking injury. Thirty-two female piglets (Landrace/Large White x synthetic sireline) were used (16 docked/16 sham-docked). Piglets were tail docked (amputation of approx. 2/3 of the tail) on post-natal day 3 using a gas hot docking iron. Equivalent sham-docked piglets served as intact controls. Pigs were euthanized by barbiturate overdose 1, 4, 8 and 16 weeks after sham/tail docking. Tail stumps (2 cm) were collected post-mortem for histopathological assessment. Caudal dorsal root ganglia (Ca1-Ca4+) and associated spinal cord were collected for gene expression analysis by real-time quantitative PCR of mRNA. Non-neural inflammatory and reparative epidermal and dermal changes associated with healing were observed after tail docking. Mild inflammation, ulceration and oedema were present at 1 week. Traumatic neuroma development was a consistent feature from 4 weeks after tail docking. Neuroma axonal dispersion in the tail stump was on-going 16 weeks after tail docking. ATF-3 mRNA was significantly upregulated in caudal DRGs up to 8 weeks after tail docking, but did not differ at 16 weeks compared with sham controls. Both CGRP and GRIN2B mRNA expression was significantly upregulated 1 week after tail docking in caudal spinal cord neurons but were not significantly different from sham-docked pigs thereafter. Histopathological lesions that occur shortly after tail docking (beyond 1 week) are not likely to induce or maintain pain. The effects of tail docking on peripheral nerve axonal proliferation and dispersion are relatively short-lived and, although still present, are attenuated by 16 weeks after tail docking injury. Changes in peripheral and spinal nociceptive processing associated with possible inflammatory and chronic pain appear to resolve by 4 weeks after tail docking injury.