Mesenchymal Stem Cell Secretome Ameliorates Hyperalgesia in a Post-operative Pain Model

Abstract BackgroundThe treatment and management of post-operative pain remain a significant challenge. There is a significant unmet need that requires novel therapeutics. The aim of this study was to investigate the effects of the mesenchymal stem cell secretome (MSC-S) in a rat incisional post-operative pain model. MethodsA post-operative pain model in rats was used to assess the human adipose-derived MSC-S therapeutic benefits. Male Sprague Dawley (SD) rats (n=40) underwent surgery whereby a 1 cm longitudinal incision was made over the plantar surface of the right hind paw where the plantaris muscle was incised longitudinally. The incision was closed with two stitches. At 1-hour post-surgery, test and control articles were administered topically for 15 minutes to the incision site. Von Frey and hotplate testing were conducted to assess mechanical and thermal pain responses, respectively. Statistical analysis of thermal and mechanical withdrawal thresholds was undertaken using an ordinary 2-way analysis of variance (ANOVA) utilising uncorrected Fishers LSD test with individual variances computed for each comparison.ResultsA statistically significant increase in thermal nociceptive threshold (analgesia) was observed in the high dose MSC-S group when compared to vehicle at 1.5 hours (p<0.0001) and 3 hours post-surgery (p<0.0001). High dose MSC-S had a more potent analgesic effect than low dose MSC-S. A statistically higher analgesic effect was observed in the high dose MSC-S group compared to morphine at the 3 hours post-surgery hot plate assessment (p<0.002). Morphine (10mg/kg) administration resulted in a significant increase in hot plate withdrawal threshold compared to vehicle at 1.5 hours (p<0.0001) and 3hours (p<0.008) post-surgery. Animals that received morphine displayed significantly less allodynia than vehicle control animals at 1.5 hours post-surgery (p<0.0001).ConclusionsThe present study demonstrated that the MSC-S topically administered in a rat post-operative pain model significantly improved thermal nociceptive thresholds. The MSC-S has potential as a non-opioid based therapy for the treatment of acute post-operative pain.