Investigations of the origins of altered pain perception in a commercial pig strain

Lameness affects over 20% of commercial pigs in the UK and is a significant threat to the sustainability of current pig production techniques worldwide, raising animal welfare, economic and food security concerns. Among the most common causes of porcine lameness are joint diseases such as osteochondrosis (OC), a skeletal disease affecting bone growth, and osteoarthritis (OA), which results from the progressive breakdown of articular cartilage. OC and OA are reported to affect over 80% of commercial pigs, however, despite this prevalence, the diseases are poorly characterised in pigs. OA also affects over 8.75 million people in the UK, so spontaneous porcine OA could provide a useful animal model of the human condition. The aims of this thesis were to characterise the pathological features of spontaneous OC and OA in a commercial pig strain, examining their relationship to pain and inflammation and identifying the molecular mechanisms involved. Spontaneous porcine OA could then be evaluated as a model for the human disease. The presence of lameness and pain-related behaviours were investigated in female commercial pigs at a number of ages between 9 and 42 months old. Knee joint OC and OA were assessed macroscopically and the synovium was examined histologically for synovitis. Expression of matrix metalloproteinases (MMP) and their inhibitors (TIMP) and pro-inflammatory cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor α (TNFα) were determined by qPCR. Cytokine protein levels were also assessed using an immunoassay. Activation of astrocytes and microglia in the lumbar spinal cord and the phenotype of primary afferent fibres in dorsal root ganglia (DRG) were examined using immunohistochemistry. Mild OC, consistent with osteochondrosis latens and manifesta, was identified in 91% of knee joints in skeletally immature pigs (9 and 15 months). OA was identified in 95% of knee joints in skeletally mature pigs (24 and 42 months) and ranged from slight cartilage erosion to end-stage disease with subchondral bone exposure. Severity of OC and OA significantly correlated with lameness, but a number of subclinical cases of both conditions were identified. It could not be confirmed whether the pain associated with porcine OC or OA was chronic, but astrocytes and microglia were generally activated suggesting there may be a chronic pain component. Synovitis was identified in 57% of knee joints and was increased in more severe OA. However, synovitis showed no correlation to OC severity, therefore mild OC may have a weaker association with inflammation than more severe forms of the disease. OC showed an unclear association with synovium pro-inflammatory cytokines, although slightly increased TNFα expression was observed. However, OC was associated with elevated MMP but unchanged TIMP expression. Increased MMP and limited inhibition by TIMP may lead to degradation of cartilage matrix components; this could help OC lesions spontaneously repair but may also leave cartilage vulnerable to further damage and disease progression. OA was associated with increased synovium pro-inflammatory cytokines but not in end-stage disease, suggesting the inflammatory profile changes as OA progresses. OA was also associated with elevated MMP and reduced TIMP expression. The increase in MMPs and their disinhibition could lead to further cartilage degeneration and worsen the OA pathology. The findings of this thesis highlight the poor state of joint health in commercial pigs and provide new insight into the involvement of inflammation and the molecular changes occurring in the synovium during spontaneous OC and OA. Spontaneous porcine OA showed a number of similarities to human OA and animal models, suggesting pigs could be a good model, however, the limited availability of healthy pigs may restrict their use. The findings of this thesis will support future studies to characterise spontaneous OC and OA in pigs, enabling these conditions to be better prevented or treated, thereby improving the sustainability of the commercial pig industry worldwide