Injury of primary afferent neurons may contribute to osteoarthritis induced pain: an experimental study using the collagenase model in rats

• Published in: Osteoarthritis and cartilage 2015-06, Vol.23 (6), p.914-924
• Main Authors: Adães, S, Ferreira-Gomes, J, Mendonça, M, Almeida, L, Castro-Lopes, J.M, Neto, F.L
• Format: Article
• Language: English
• Subjects: Amines - pharmacology; Analgesics - pharmacology; Animal model; Animals; Arthritis, Experimental - complications; Arthritis, Experimental - pathology; Arthritis, Experimental - physiopathology; Calcium Channels - metabolism; Calcium Channels, L-Type; CatWalk; Collagenases; Cyclohexanecarboxylic Acids - pharmacology; gamma-Aminobutyric Acid - pharmacology; Ganglia, Spinal - metabolism; Knee-Bend; Male; Motor Activity - physiology; Movement-induced nociception; Neuronal injury; Neurons, Afferent - physiology; Nociception - drug effects; Nociception - physiology; Nociceptive Pain - etiology; Nociceptive Pain - pathology; Nociceptive Pain - physiopathology; Osteoarthritis - complications; Osteoarthritis - pathology; Osteoarthritis - physiopathology; Rats; Rats, Wistar; Rheumatology
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2015.02.010

Summary Objective Pain exacerbated by movement and loading on the joint is the major symptom of osteoarthritis (OA), but the mechanisms of chronic pain in this pathology are still poorly understood. Using the intra-articular (i.a.) injection of collagenase in the knee of rats as a model of OA, we aimed at evaluating whether injury of sensory neurons may contribute to the development of OA-associated nociception. Design OA was induced by i.a. injection of collagenase into the left knee joint of adult male Wistar rats. Histopathological changes and movement and loading-induced nociception were assessed for 6 weeks. A time-course analysis of the expression of the neuronal injury markers activating transcription factor-3 (ATF-3) and neuropeptide Y (NPY) and of the neuropeptide SP in the dorsal root ganglion (DRG) was performed. Gabapentin's effect on nociception was evaluated, as well as the expression of the α2δ-1 voltage-gated calcium channel subunit. Results Collagenase induced the development of OA-like histopathological changes and of movement-induced nociception. Altered expression of ATF-3, NPY and SP was observed in the DRG, correlating with the degree of articular degeneration after 6 weeks of disease progression. Repeated administration of gabapentin reversed the nociceptive responses 6 weeks after the induction of OA. α2δ-1was upregulated in the DRG. Conclusion By inducing nociceptive behaviours associated with relevant joint structural changes, the i.a. injection of collagenase presents itself as a pertinent model for the study of OA pain. The findings in this study support the hypothesis that injury of sensory neurons innervating OA joints may be a significant element in the mechanisms of OA-associated pain.