title: Platelet-rich plasma exerts antinociceptive activity by a peripheral endocannabinoid-related mechanism.
abstract: In regenerative medicine, platelet by-products containing factors physiologically involved in wound healing, have been successfully used in the form of platelet-rich plasma (PRP) for the topical therapy of various clinical conditions since it produces an improvement in tissue repair as well as analgesic effects. Measurement of endocannabinoids and related compounds in PRP revealed the presence of a significant amount of anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide. Investigation of the activity of PRP on the keratinocyte cell line NCTC2544 in physiological and inflammatory conditions showed that, under inflammatory conditions, PRP induced in a statistically significant manner the production of these compounds by the cells suggesting that PRP might induce the production of these analgesic mediators particularly in the physiologically inflamed wounded tissue. Studies in a mouse model of acute inflammatory pain induced by formalin injection demonstrated a potent antinociceptive effect against both early and late nocifensive responses. This effect was observed following intrapaw injection of (1) total PRP; (2) lipids extracted from PRP; and (3) an endocannabinoid-enriched lipid fraction of PRP. In all conditions, antagonists of endocannabinoid CB1 and CB2 receptors, injected in the paw, abrogated the antinociceptive effects strongly suggesting for this preparation a peripheral mechanism of action. In conclusion, we showed that PRP and PRP lipid extract exert a potent antinociceptive activity linked, at least in part, to their endocannabinoids and related compound content, and to their capability of elevating the levels of these lipid mediators in cells.
authors.affiliation: DIMES, University of Genova, Largo Rosanna Benzi 10, Genoa, Italy. fiorella.descalzi@istge.it
authors.forename: Fiorella
authors.initials: F
authors.lastname: Descalzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Ulivi
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.forename: Luisa
authors.initials: L
authors.lastname: Gatta
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000577:Amides; D000700:Analgesics / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D063388:Endocannabinoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D004983:Ethanolamines / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009829:Oleic Acids / Q000737:chemistry; D010146:Pain / Q000188:drug therapy; D010169:Palmitic Acids / Q000737:chemistry; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000737:chemistry
chemical_list: D000577:Amides; D000700:Analgesics; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C005958:palmidrol; C094503:glyceryl 2-arachidonate; C078814:anandamide