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<article dtd-version="3.0" article-type="Invited Methods Article - JoVE Produced Video">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher">jove</journal-id>
      <journal-id journal-id-type="email">editorial-office@jove.com</journal-id>
      <journal-title-group>
        <journal-title>Journal of Visualized Experiments</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">1940-087X</issn>
      <issn pub-type="epub"></issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JoVE59024</article-id>
      <article-id pub-id-type="manuscript">JoVE59024</article-id>
      <article-categories>
        <subj-group subj-group-type="Article Type">
          <subject>Invited Methods Article - JoVE Produced Video</subject>
        </subj-group>
        <subj-group subj-group-type="Category">
          <subject>JoVE Medicine</subject>
        </subj-group>
        <subj-group subj-group-type="Classification">
          <subject>Neurologic Manifestations</subject>
          <subject>Pain</subject>
          <subject>Chronic Pain</subject>
          <subject>Joint Diseases</subject>
          <subject>Arthritis</subject>
          <subject>Arthritis, Rheumatoid</subject>
          <subject>Osteoarthritis</subject>
          <subject>Diseases</subject>
          <subject>Nervous System Diseases</subject>
          <subject>Musculoskeletal Diseases</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Spontaneous and Evoked Measures of Pain in Murine Models of Monoarticular Knee Pain.</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes">
          <role content-type="1" />
          <name>
            <surname>Krug</surname>
            <given-names>Hollis</given-names>
          </name>
          <email>Hollis.Krug@va.gov</email>
          <xref ref-type="aff" rid="aff1" />
          <xref ref-type="aff" rid="orcid3" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="2" />
          <name>
            <surname>Dorman</surname>
            <given-names>Christopher</given-names>
          </name>
          <email>christopher.dorman@va.gov</email>
          <xref ref-type="aff" rid="aff2" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="3" />
          <name>
            <surname>Blanshan</surname>
            <given-names>Nicole</given-names>
          </name>
          <email>nicole.blanshan@va.gov</email>
          <xref ref-type="aff" rid="aff3" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="4" />
          <name>
            <surname>Frizelle</surname>
            <given-names>Sandra</given-names>
          </name>
          <email>sandra.frizelle@va.gov</email>
          <xref ref-type="aff" rid="aff4" />
        </contrib>
        <contrib contrib-type="author">
          <role content-type="5" />
          <name>
            <surname>Mahowald</surname>
            <given-names>Maren</given-names>
          </name>
          <email>mahow001@gmail.com</email>
          <xref ref-type="aff" rid="aff5" />
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Navani</surname>
            <given-names>Dipesh</given-names>
          </name>
          <degrees>Ph.D.</degrees>
          <email>dipesh.n@jove.com</email>
          <xref ref-type="aff" rid="aff6" />
        </contrib>
        <aff id="aff1">
          <institution>Minneapolis VAHCS</institution>
          <institution content-type="dept">MEdicine</institution>
          <addr-line content-type="addrline1">One Veterans Drive</addr-line>
          <addr-line content-type="addrline2">Rheumatology (111R)</addr-line>
          <country>UNITED STATES</country>
          <addr-line content-type="city">Minneapolis</addr-line>
          <addr-line content-type="state">MN</addr-line>
          <addr-line content-type="zipcode">55417</addr-line>
          <institution>University of Minnesota</institution>
        </aff>
        <aff id="orcid3">0000-0001-8285-5202</aff>
        <aff id="aff2">
          <institution>Minneapolis VAHCS</institution>
          <addr-line content-type="addrline1">One Veterans Drive</addr-line>
          <country>UNITED STATES</country>
          <addr-line content-type="city">Minneapolis</addr-line>
          <addr-line content-type="zipcode">55417</addr-line>
          <institution>Research Department, VA Health Care Center, Minneapolis, MN, USA</institution>
        </aff>
        <aff id="aff3">
          <institution>Minneapolis VAHCS</institution>
          <addr-line content-type="addrline1">One Veterans Drive</addr-line>
          <country>UNITED STATES</country>
          <addr-line content-type="city">Minneapolis</addr-line>
          <addr-line content-type="zipcode">55417</addr-line>
          <institution>Research Department, VA Health Care Center, Minneapolis, MN, USA</institution>
        </aff>
        <aff id="aff4">
          <institution>Minneapolis VAHCS</institution>
          <addr-line content-type="addrline1">One Veterans Drive</addr-line>
          <country>UNITED STATES</country>
          <addr-line content-type="city">Minneapolis</addr-line>
          <addr-line content-type="zipcode">55417</addr-line>
          <institution>Research Department, VA Health Care Center, Minneapolis, MN, USA</institution>
        </aff>
        <aff id="aff5">
          <institution>Minneapolis VAHCS</institution>
          <addr-line content-type="addrline1">One Veterans Drive</addr-line>
          <country>UNITED STATES</country>
          <addr-line content-type="city">Minneapolis</addr-line>
          <addr-line content-type="zipcode">55417</addr-line>
          <institution>Department of Medicine, University of Minnesota, Minneapolis, MN, USA. Research Department, VA Health Care Center, Minneapolis, MN, USA</institution>
        </aff>
        <aff id="aff6">
          <institution>JoVE</institution>
          <addr-line>1 Alewife Center</addr-line>
          <addr-line>Suite 200</addr-line>
          <addr-line>Cambridge, MA  02140</addr-line>
          <country>UNITED STATES</country>
        </aff>
      </contrib-group>
      <history>
        <date date-type="received">
          <day>30</day>
          <month>08</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>10</day>
          <month>11</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>07</day>
          <month>11</month>
          <year>2018</year>
        </date>
        <date date-type="accepted">
          <day>13</day>
          <month>11</month>
          <year>2018</year>
        </date>
      </history>
      <abstract>
        <p>Pain is the main cause of disability from arthritis. There is currently an unmet need for adequate treatments for arthritis pain. Pre-clinical models are necessary and useful for studying the mechanisms of pain and for evaluating efficacy of arthritis therapies. Measuring pain in animal models of arthritis is challenging. We have developed methods for measuring evoked and spontaneous pain in three models of murine arthritis. We quantitate the evoked pain responses of mice subjected to firm palpation of a painful knee. We also evaluate spontaneous pain by the proportion of weight and the amount of time placed on each of their 4 limbs after induction of arthritis pain in one knee. Joint pain in these mouse models produces a significant increase in evoked pain responses and an alteration in weight bearing. Since mice are quadrupeds, they offload the painful limb to the contralateral limb, to the forelimbs or some combination. These methods are simple, require minimal equipment, and are reproducible and sensitive for detecting pain. They are useful for studying both disease modifying arthritis treatments and analgesics in mice.</p>
      </abstract>
      <kwd-group>
        <kwd>mouse</kwd>
        <kwd>arthritis</kwd>
        <kwd>pain</kwd>
        <kwd>Animal Models</kwd>
        <kwd>joint</kwd>
        <kwd>behavior</kwd>
      </kwd-group>
      <funding-group />
      <counts>
        <fig-count count="0" />
      </counts>
      <custom-meta-group>
        <custom-meta>
          <meta-name>Please indicate whether this article will be Standard Access or Open Access. </meta-name>
          <meta-value>Standard Access (US$2,400);</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Please indicate the &lt;b&gt; city, state/province, and country&lt;/b&gt; where this article will be &lt;b&gt;filmed&lt;/b&gt;. Please do not use abbreviations.</meta-name>
          <meta-value>Minneapolis, MN, USA</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Black and White Image Count</meta-name>
          <meta-value>0</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Color Image Count</meta-name>
          <meta-value>0</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Production Notes</meta-name>
          <meta-value>RE: Author's notes regarding section 4 of the protocol: "We believe this is essentially the most crucial part of this paper to share with readers as it is technically highly reliant on technique. Please understand that the reason this is difficult is that the pain is very mild so that it is hard to discern when the animals are actually in pain and when they are just uncomfortable being restrained. I think once you see what we are doing, it will not be disturbing to film. But alternatively, demonstrating placement and restraint technique would be helpful. Video graphics depicting the types of pain responses we grade might be an acceptable substitute."
So, it may be acceptable to film, but probably more thorough vet review and IACUC review as well is warranted.</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Acquisitions Editor</meta-name>
          <meta-value>ronald myers</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>Assistant who entered lead</meta-name>
          <meta-value>n/a</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>ALA Access Type</meta-name>
          <meta-value>JPV Open Access ($4200)</meta-value>
        </custom-meta>
        <custom-meta>
          <meta-name>ALA Comment</meta-name>
          <meta-value>See author's note-they say it has to be open but have checked standard - LS: Invoiced Open per note. Asking for updated ALA</meta-value>
        </custom-meta>
      </custom-meta-group>
    </article-meta>
  </front>
  <body>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 1.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 2a.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 2b.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 3a.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 3b.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <table-wrap>
      <label>Table of Materials</label>
      <graphic xlink:href="Copy of JoVE_Materials.xlsx" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </table-wrap>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 1.tif" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 2.tif" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure</label>
      <graphic xlink:href="Figure 3.tif" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <table-wrap>
      <label>Table of Materials</label>
      <graphic xlink:href="Copy of essential supplies table.xlsx" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </table-wrap>
    <fig>
      <label>Figure 1</label>
      <graphic xlink:href="Fig 1.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure 2</label>
      <graphic xlink:href="Fig 2.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <fig>
      <label>Figure 3</label>
      <graphic xlink:href="Fig 3.pdf" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </fig>
    <table-wrap>
      <label>Table of Materials</label>
      <graphic xlink:href="Table of Materials 111318.xlsx" xmlns:xlink="http://www.w3.org/1999/xlink" />
    </table-wrap>
  </body>
</article>