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Prolonged Amelioration of Experimental Postoperative Pain by Bupivacaine Released From Microsphere-Coated Hernia Mesh
  1. Rachit Ohri, PhD*,
  2. Jeffery Chi-Fei Wang, MD,
  3. Lan Pham, MS*,
  4. Phillip D. Blaskovich, BS*,
  5. Daniel Costa, BS*,
  6. Gary Nichols, PhD,
  7. William Hildebrand, MS,
  8. Nelson Scarborough, PhD*,
  9. Clifford Herman, PhD and
  10. Gary R. Strichartz, PhD
  1. *Covidien Surgical Solutions, Bedford, MA
  2. Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
  3. Mallinckrodt Pharmaceuticals, St. Louis, MO
  1. Address correspondence to: Gary R. Strichartz, PhD, Brigham and Women’s Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, 75 Francis St, MRB 613, Boston, MA 02115-6110 (e-mail: gstrichartz{at}partners.org).

Abstract

Background and Objectives 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.

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Footnotes

  • The authors declare no conflict of interest.

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