119
presentedalong withLII inthegait patternanalysisto measureOA-
related pain development in the ACLT model.Ifthere is aswitch of
limb idling strategies or compensatory changes, evaluations on
individual ratios and LII will provide more information.
There are several limitations for the use of LII to measure
symptomatic OA in animal model. Firstly, it is only applicable for
unilateral injury. Any unanticipated changes on the contralateral
limb would have chance to confound the assessment of limb idle-
ness, such as spontaneous development of primary OA.
Buprenorphine-sensitivechanges inLII may mean changes inpain
levels in target side or contralateral side. Therefore, it is important
toassessthestatusofcontralateral sidewhenLII isusedtomeasure
painful responses in animal model of unilateral injury. Secondly,
although we detected significant correlations between LII and
osteoarthritic structural changes, the mere co-existence of OA
changes and gait changes at one single time point might not
provide strong evidence for association. Longitudinal studies that
include data from more time points would be more appropriate.
Thirdly, LII only reveals activity-related pain,whilepaininOA may
have other elements which are not activity-related
18
.Thus LII may
reveal only parts ofthe whole picture for the development ofpain
medication in animal model. Finally, other functional changes
which are not related to pain may also affect limb idleness, for
example, knee stiffness, extension deficit or altered limb coordi-
nationmay leadto changesin gait parameters andaffectsymmetry
in walking gait. Although LII cannot differentiate different painful
conditions (OA vs tendinopathies) that trigger limb idleness, it is
possible to extend the use of LII for evaluation of functional
recovery as a restoration of gait symmetry after unilateral injury,
such as tendon injuries, muscle weakness or some neural injuries.
Further exploration on the use of LII to monitor limb functional
recovery in animal models is possible.
Conclusion
LII isauseful parameterto measureOA-relatedkneepaininarat
model.
Author contributions
Experimental design and intellectual input: SCF, KMC,LKH.
Data acquisition, analysis, manuscript writing: SCF, YCC.
Final approval ofmanuscript: All authors.
Role of funding source
This study was supported by the Direct Grant (Reference No.:
2010.2.041) from The Chinese University of Hong Kong.
Conflicts of interest
All authors declare no conflicts of interest.
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Please cite this article in press as: Fu SC, et al., Limb Idleness Index (LII): a novel measurement of pain in a rat model of osteoarthritis,
Osteoarthritis and Cartilage (2012), http://dx.doi.org/10.1016/j.joca.2012.08.006
Appendix IIIB