Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain
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 in...
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| Veröffentlicht in: | Life sciences (1973) 2023-07, Vol.324, p.121736-121736, Article 121736 |
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| container_title | Life sciences (1973) |
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| creator | Murakami, Toru Ishida, Takashi Tanaka, Satoshi Nakayama, Jun Tsurugizawa, Tomokazu Takahashi, Yukari Kato, Fusao Kawamata, Mikito |
| description | 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 |
| doi_str_mv | 10.1016/j.lfs.2023.121736 |
| format | Article |
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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.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2023.121736</identifier><identifier>PMID: 37121542</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>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</subject><ispartof>Life sciences (1973), 2023-07, Vol.324, p.121736-121736, Article 121736</ispartof><rights>2023 The Authors</rights><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-cdae862bbc7a7dcfacb86e2476c5ea719f45e5b3f54ae6b3b37c5a705cfbc7c93</citedby><cites>FETCH-LOGICAL-c462t-cdae862bbc7a7dcfacb86e2476c5ea719f45e5b3f54ae6b3b37c5a705cfbc7c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320523003703$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37121542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murakami, Toru</creatorcontrib><creatorcontrib>Ishida, Takashi</creatorcontrib><creatorcontrib>Tanaka, Satoshi</creatorcontrib><creatorcontrib>Nakayama, Jun</creatorcontrib><creatorcontrib>Tsurugizawa, Tomokazu</creatorcontrib><creatorcontrib>Takahashi, Yukari</creatorcontrib><creatorcontrib>Kato, Fusao</creatorcontrib><creatorcontrib>Kawamata, Mikito</creatorcontrib><title>Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>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.</description><subject>Adjuvant-induced arthritis</subject><subject>Animals</subject><subject>Bone afferent neurons</subject><subject>Bone Marrow - pathology</subject><subject>Disease Models, Animal</subject><subject>Electrophysiology</subject><subject>Hyperalgesia - etiology</subject><subject>Inflammation - complications</subject><subject>Lidocaine</subject><subject>Local anesthetics</subject><subject>Male</subject><subject>Nociceptors</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis - pathology</subject><subject>Osteoarthritis pain</subject><subject>Pain - etiology</subject><subject>Pain - pathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Wide dynamic range neuron</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEURYMoTk_rD3AjWbqpNh-VSjWuZBidgQE3ug4vqRcmTVXSJukWXfjbTVOjSyEQSM69cA8hbzjbccaH94fd7MtOMCF3XHAth2dkw0e979gg-XOyYUz0nRRMXZHrUg6MMaW0fEmupG686sWG_L6PfoZlgRpSpBAnWk624PcTxkpjcsHhsaZMC8YSavi1ciHS-ojUpoh0gZzTDwoZ2_M5zWecLv9wOWGBmS5pwpkmT1OpmCDXx9yaCj1CiK_ICw9zwddP95Z8-3T79eaue_jy-f7m40Pn-kHUzk2A4yCsdRr05Dw4Ow4oej04haD53vcKlZVe9YCDlVZqp0Az5XyLuL3ckndr7zGntq1Us4TicJ4hYjoVI0Y2NoNjk7glfEVdTqVk9OaY247803BmLtrNwTTt5qLdrNpb5u1T_ckuOP1L_PXcgA8rgG3kOWA2xQWMDqeQ0VUzpfCf-j_YAJbt</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Murakami, Toru</creator><creator>Ishida, Takashi</creator><creator>Tanaka, Satoshi</creator><creator>Nakayama, Jun</creator><creator>Tsurugizawa, Tomokazu</creator><creator>Takahashi, Yukari</creator><creator>Kato, Fusao</creator><creator>Kawamata, Mikito</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20230701</creationdate><title>Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain</title><author>Murakami, Toru ; Ishida, Takashi ; Tanaka, Satoshi ; Nakayama, Jun ; Tsurugizawa, Tomokazu ; Takahashi, Yukari ; Kato, Fusao ; Kawamata, Mikito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-cdae862bbc7a7dcfacb86e2476c5ea719f45e5b3f54ae6b3b37c5a705cfbc7c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adjuvant-induced arthritis</topic><topic>Animals</topic><topic>Bone afferent neurons</topic><topic>Bone Marrow - pathology</topic><topic>Disease Models, Animal</topic><topic>Electrophysiology</topic><topic>Hyperalgesia - etiology</topic><topic>Inflammation - complications</topic><topic>Lidocaine</topic><topic>Local anesthetics</topic><topic>Male</topic><topic>Nociceptors</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis - pathology</topic><topic>Osteoarthritis pain</topic><topic>Pain - etiology</topic><topic>Pain - pathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Wide dynamic range neuron</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murakami, Toru</creatorcontrib><creatorcontrib>Ishida, Takashi</creatorcontrib><creatorcontrib>Tanaka, Satoshi</creatorcontrib><creatorcontrib>Nakayama, Jun</creatorcontrib><creatorcontrib>Tsurugizawa, Tomokazu</creatorcontrib><creatorcontrib>Takahashi, Yukari</creatorcontrib><creatorcontrib>Kato, Fusao</creatorcontrib><creatorcontrib>Kawamata, Mikito</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murakami, Toru</au><au>Ishida, Takashi</au><au>Tanaka, Satoshi</au><au>Nakayama, Jun</au><au>Tsurugizawa, Tomokazu</au><au>Takahashi, Yukari</au><au>Kato, Fusao</au><au>Kawamata, Mikito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>324</volume><spage>121736</spage><epage>121736</epage><pages>121736-121736</pages><artnum>121736</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>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.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>37121542</pmid><doi>10.1016/j.lfs.2023.121736</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Life sciences (1973), 2023-07, Vol.324, p.121736-121736, Article 121736 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| 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 |
| title | Inflammation and subsequent nociceptor sensitization in the bone marrow are involved in an animal model of osteoarthritis pain |
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