title: Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.
abstract: OBJECTIVE
  Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery.
  
  
  METHODS
  Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days.
  
  
  RESULTS
  Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated before the incision (group VI) reduced hypersensitivity for only approximately 2 hours, an overall insignificant effect.
  
  
  CONCLUSIONS
  Bupivacaine slowly released for 72 hours from microspheres adsorbed to the hernia mesh significantly suppresses evoked postoperative hypersensitivity for at least 1 week and is more effective than a suspension of these microspheres or preoperative single-shot infiltration of bupivacaine.
authors: From the *Covidien Surgical Solutions, Bedford, MA; †Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and ‡Mallinckrodt Pharmaceuticals, St. Louis, MO.
authors: Rachit
authors: R
authors: Ohri
authors: Jeffery Chi-Fei
authors: JC
authors: Wang
authors: Lan
authors: L
authors: Pham
authors: Phillip D
authors: PD
authors: Blaskovich
authors: Daniel
authors: D
authors: Costa
authors: Gary
authors: G
authors: Nichols
authors: William
authors: W
authors: Hildebrand
authors: Nelson
authors: N
authors: Scarborough
authors: Clifford
authors: C
authors: Herman
authors: Gary R
authors: GR
authors: Strichartz
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage*; D004343:Drug Implants; D008297:Male; D008863:Microspheres; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010149:Postoperative Pain / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013526:Surgical Mesh; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D004343:Drug Implants; D002045:Bupivacaine