Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain

• Published in: Life sciences (1973) Vol. 324; p. 121736
• Main Authors: Murakami, Toru, Ishida, Takashi, Tanaka, Satoshi, Nakayama, Jun, Tsurugizawa, Tomokazu, Takahashi, Yukari, Kato, Fusao, Kawamata, Mikito
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2023
• Subjects: Adjuvant-induced arthritis; Animals; Bone afferent neurons; Bone Marrow - pathology; Disease Models, Animal; Electrophysiology; Hyperalgesia - etiology; Inflammation - complications; Lidocaine; Local anesthetics; Male; Nociceptors; Osteoarthritis; Osteoarthritis - pathology; Osteoarthritis pain; Pain - etiology; Pain - pathology; Rats; Rats, Sprague-Dawley; Wide dynamic range neuron; Osteoarthritis pain; Adjuvant-induced arthritis; Electrophysiology; Wide dynamic range neuron; Lidocaine; Osteoarthritis; Bone afferent neurons; Local anesthetics
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121736

This study aimed to determine whether pathological changes in the bone marrow cause Osteoarthritis (OA) pain based on magnetic resonance imaging (MRI), immunohistochemistry, and electrophysiology. Adjuvant-induced arthritis (AIA) was achieved by injecting 150 μL of complete Freund's adjuvant into the right knee joints of male Sprague-Dawley rats. AIA rats were compared with saline-injected rats. AIA significantly induced mechanical hyperalgesia and spontaneous pain in the right hind paw 1–14 days after induction. Intratibial injection of 50 μL of 1 % lidocaine significantly suppressed AIA-induced mechanical hyperalgesia (p = 0.0001) and spontaneous pain (p = 0.0006) 3 days after induction. In T2-weighted MRI, AIA induced high-signal intensity within the proximal tibial metaphysis, and the mean T2 values in this area significantly increased on days 3 (p = 0.0043) and 14 (p = 0.0012) after induction. AIA induced intraosseous edema and significantly increased the number of intraosseous granulocytes on days 3 (p < 0.0001) and 14 (p < 0.0001) after induction. The electrophysiological study on days 3–7 after induction showed significantly increased spontaneous firing rates (p = 0.0166) and evoked responses to cutaneous stimuli (brush, p < 0.0001; pinching, p = 0.0359) in the right hind paw plantar surface and intratibial stimuli (p = 0.0002) in wide-dynamic-range neurons of the spinal dorsal horn. Intraosseous changes caused by OA induce hypersensitivity in the sensory afferents innervating bone marrow may be involved in OA pain. Novel bone marrow-targeted therapies could be beneficial for treating OA pain. •We studied bone marrow pathological changes implicated in osteoarthritis (OA) pain.•Adjuvant-induced arthritis (AIA) induced inflammatory changes in the bone marrow.•Intratibial lidocaine injection suppressed AIA-induced pain-related behaviors.•AIA increased the firing rate of the spinal dorsal horn to intramedullary stimuli.•Intraosseous changes due to OA induced hypersensitivity and are involved in OA pain.