Analgesic properties of calcium phosphate apatite loaded with bupivacaine on postoperative pain.
Synthetic calcium-deficient apatites (CDA) are structurally similar to biological apatites and are well known as chemical precursors of biphasic calcium phosphates (BCP). BCP are mixtures of hydroxyapatite and beta-tricalcium phosphate and are widely used as bone substitutes in human surgery. Bupivacaine, a local anesthetic, has been loaded onto CDA using isostatic compaction. The purpose of this study was to evaluate the in vivo performance of such a local release on pain after having previously defined the in vitro release profile of bupivacaine. CDA was loaded with 1%, 4%, and 16% of bupivacaine using an isostatic compaction process. In vitro release profile assays performed indicated the complete release of bupivacaine after 24 h. Wistar male rats received 50 mg implants of CDA associated, respectively, with 0, 1%, 4%, and 16% of bupivacaine into the distal femur. Analgesia was measured using the electronic version of the Von Frey monofilament test, assessing the inflammatory response and a neurological score. During the first postoperative days, a dose-dependent analgesic effect was observed with the bupivacaine adsorbed on the resorbable implant. This combined device system thus appears to release local anesthetic in a manner that prevents or limits postoperative pain following bone surgery. This innovative approach could be integrated into a global pain management program, for example, in the context of bone harvesting where bone reconstruction is required.
Nantes Atlantique Universités, INSERM UMR 791, LIOAD, BP 84215, 44042 Nantes, France.
Elise
E
Verron
Olivier
O
Gauthier
Pascal
P
Janvier
Herve
H
Le Guen
Delphine
D
Holopherne
Remi
R
Cavagna
Jean-Michel
JM
Bouler
D000698:Analgesia; D000779:Anesthetics, Local / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001031:Apatites / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D002045:Bupivacaine / Q000737:chemistry / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008422:Materials Testing; D010149:Postoperative Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D000779:Anesthetics, Local; D001031:Apatites; D001672:Biocompatible Materials; D002130:Calcium Phosphates; D004337:Drug Carriers; D002045:Bupivacaine