Effect of Conditioned Pain Modulation on Somatosensory Profile in Surgical Models of Osteoarthritis Pain in Rats and Dogs

Introduction: The objective was to compare the effect of conditioning stimulus (CS) on somatosensory changes in animal models of osteoarthritis (OA) pain.

Materials and Methods: OA model was surgically induced in right hind stifle at day (D) 0. Rats (n = 48/Sprague-Dawley/female/ovariectomized–OVX–) were divided in four groups: OA-OVX placebo/ OA-OVX positive analgesic–PA–: pregabalin; oral; 30 mg/kg and carprofen; subcutaneous; 5 mg/kg/naïve-OVX/naïve-normal. OA-dogs (n = 6/sterilized: female = 4; male = 2) received a placebo. Quantitative sensory testing (QST) included punctate tactile (rats; paw withdrawal threshold (PWT); D–1; D7; D14; D21; D35; D49: D56) and mechanical (dogs; D–1, week–W–4; W7; W9) allodynia evaluation, pre- and post-CS. Mixed model and Student’s t tests were applied (α = 0.05).

Results: Dynamic CS increased QST (D–1) threshold in rats (p < 0.023), but not in dogs (p > 0.922). Secondary allodynia (ipsilateral) was noted in OA rats (D7; p < 0.035) and in placebo group (D7-D56). CS increased PWT in placebo group, corresponding to an efficient conditioning pain modulation (CPM) (D21; D35; p > 0.107). Central sensitization (contralateral) was observed in placebo rats compared with PA (D14) and all other groups (D56); p < 0.004. The post-CS contralateral PWT increase counteracted the secondary allodynia present pre-CS (p > 0.062). An efficient CPM effect was observed for all time-points in PA and placebo OA rats. Primary allodynia was present in OA dogs at W4 with a nadir at W7; p = 0.038 without a CPM effect.

Discussion: OA animals developed allodynia, supporting peripheral and central sensitization. Post-CS response was variable in rats within time, supporting a possible fatigue in CPM (activation–alteration). In laboratory dogs, the stress-induced analgesia (baseline) complexified the CPM manifestation.

Acknowledgements: The authors would like to thank ArthroLab’s personnel for their technical assistance. There was not proprietary interest or funding provided for this project. Dr. Beatriz Monteiro is a recipient of the Vanier Canada Graduate Scholarship.