1. Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain 
J.J. McDougall, S. Albacete, N. Schuelert, P.G. Mitchell, C. Lin, J.L. Oskins, H.H. Bui, M.G. Chambers 
Osteoarthritis and Cartilage 
Volume 25, Issue 6, Pages (June 2017)
DOI: /j.joca
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

2. Fig. 1
Concentration of LPA in human synovial fluid taken from normal knees as well as knees with either mild, moderate or severe OA. Intra-articular LPA levels rose as OA severity increased. (****P <  one-way ANOVA with Dunnett's post hoc test). Data are means ± S.E.M. (n = 11–21 patients/group).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

3. Fig. 2
(A): Electron micrographs of saphenous nerve sections taken from rats treated with either vehicle, LPA, or a combination of LPA and the LPA antagonist Ki Myelin sheath thickness decreased at day 21 following LPA administration which was inhibited by co-administration of Ki (B): G-ratio calculations showing that LPA caused significant demyelination (i.e., greater G-ratio value) which could be blocked by co-injection of Ki (***P < 0.001 one-way ANOVA with Tukey's post hoc test). Data are means ± S.E.M. (n = 321–581 neurones from three animals).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

4. Fig. 3
(A): Immunohistochemical micrographs of DRGs stained with the nerve injury marker ATF-3. Cell bodies were harvested at day 21 from control (vehicle), LPA, and LPA + the LPA1 receptor antagonist Ki treated animals. (B): Percentage of DRGs that stained positive for ATF-3 was increased in LPA-treated rats. This neurodegenerative effect was blocked by Ki (*P < 0.05 Kruskal–Wallis test with Dunn's multiple comparisons test). Data are means ± S.E.M. (n = 180–295 sections from three animals).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

5. Fig. 4
(A): Reduction in saphenous nerve conduction velocity following LPA treatment indicative of demyelination. (*P < 0.05, unpaired Student t-test). (B): Firing frequency of joint afferents in response to knee rotation by different levels of torque. Compared to vehicle, LPA increased joint mechanosensitivity, but only during hyper-rotation of the knee. (**P.0.01 Two-way ANOVA with Bonferroni post hoc test). Data are means ± S.E.M. (n = 8–9 rats).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

6. Fig. 5
(A): Time-course showing a weight bearing deficit in response to intra-articular injection of different doses of LPA compared to vehicle treated knees. (B): Inhibition of the pro-nociceptive effect of LPA by pre-treatment of animals with Ki (****P <  one-way ANOVA). Data are means ± S.E.M. (n = 5 rats/group).
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

7. Fig. 6
Treatment of MIA rats with Ki reduced saphenous nerve g-ratio measurements (A), DRGs ATF-3 expression (B), and pain behaviour (C) indicating an anti-neuropathic effect of LPA receptor blockade in OA joints. By day 71, MIA rats exhibited a robust pain response which was unresponsive to diclofenac treatment, but could be inhibited by Ki (D). (*P < 0.05, ***P < 0.001, ****P <  Student's t-test or Mann–Whitney test). Data are means ± S.E.M.
Osteoarthritis and Cartilage  , DOI: ( /j.joca )
Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions