Description of Novel Molecular Factors in Lumbar DRGs and Spinal Cord Factors Underlying Development of Neuropathic Pain Component in the Animal Model of Osteoarthritis

• Published in: Molecular neurobiology Vol. 61; no. 3; pp. 1580 - 1592
• Main Authors: Malek, Natalia, Mlost, Jakub, Kostrzewa, Magdalena, Rajca, Jolanta, Starowicz, Katarzyna
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2024; Springer Nature B.V
• Subjects: Animal models; Animals; Arthritis; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cord Factors - metabolism; Disease Models, Animal; Dorsal root ganglia; Drug therapy; Ganglia, Spinal - metabolism; Gene expression; Humans; Knee; Male; Neuralgia; Neuralgia - metabolism; Neurobiology; Neurology; Neuropeptide Y; Neurosciences; Osteoarthritis; Osteoarthritis - complications; Osteoarthritis - diagnostic imaging; Osteoarthritis - metabolism; Pain; Pain perception; Phenotypes; Rats; Rats, Sprague-Dawley; Rats, Wistar; Spinal cord; Spinal Cord - metabolism; Behavioral studies; Osteoarthritis pain; MIA model; Pain chronicity factors expression; Neuropathic pain component; Knee microtomography
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-023-03619-x

Osteoarthritis (OA) is one of the most common joint disorder, with pain accompanied by functional impairment, as the most pronounced clinical symptom. Currently used pharmacotherapy involves symptomatic treatment that do not always provide adequate pain relief. This may be due to concomitance of central sensitization and development of neuropathic features in OA patients. Here we performed studies in the animal model of OA to investigate of the neuropathic component. Intraarticular injection of monoiodoacetate (MIA, 1 mg) was used to induce OA in Wistar male rats. Development of pain phenotype was assessed by behavioral testing (PAM test and von Frey’s test), while corresponding changes in dorsal root ganglia (DRGs L3–L5) and spinal cord (SC) gene expression were assessed by means of qRT-PCR technique. We also performed microtomography of OA-affected knee joints to correlate the level of bone degradation with observed behavioral and molecular changes. We observed gradually developing remote allodynia after MIA treatment, indicating the presence of neuropathic component. Our results showed that, among DRGs innervating knee joint, development of central sensitization is most likely due to peripheral input of stimuli through DRG L5. In SC, development of secondary hypersensitivity correlated with increased expression of TAC1 and NPY. Our studies provided molecular records on abnormal activation of pain transmission markers in DRG and SC during development of OA that are responsible for the manifestation of neuropathic features. The obtained results increase insight into molecular changes occurring in the neuronal tissue during OA development and may contribute to readdressing treatment paradigms.