An effective buprenorphine analgesic protocol increases post-operative adhesions in rats after laparotomy

Abstract

The use of analgesics in post-operative adhesion (POA) research is problematic due to POA-inhibiting effects of anti-inflammatory agents and bowel motility-inhibiting effects of opioids, which may increase adhesion formation. This study was conducted to assess a buprenorphine (BUP) protocol for analgesic efficacy and its effects on POA formation in a rat cecal abrasion model. The protocol was approved by the University of Florida's Institutional Animal Care and Use Committee (IACUC). Forty-one female Sprague-Dawley rats were randomized into two groups (n = 20 or 21 group). Body weight, food and water intake were recorded daily from 2 days before until 7 days after surgery. Treatment rats received 0.05 mg kg–1 BUP SQ at anesthesia induction and 0.3 mg kg–1 BUP orally in flavored gelatin 6 hours after surgery. Control rats received saline placebo injection and plain gelatin. All rats underwent laparotomy and controlled cecal abrasion. At 3, 6 and 24 hours post-operatively rats were individually observed in 10-minutes periods for pain related behavior incidence: ‘twitch’ (contraction of muscles along dorsum and/or head), ‘back arch’ (cat-like position with front legs extended and pushing backward), ‘writhe’ (flank contraction), and ‘stagger/fall’ (momentary loss of balance while grooming or ambulating), using the method of Roughan and Flecknell (Pain 2001,90, 65–74). On post-op day seven rats were euthanized by CO2 inhalation and POA evaluated (0 to 4 scale; ³Grade 2 = clinically significant.) BUP treated rats had lower mean pain scores than control rats at 3 hours (1.6 ± 1.7 versus 20.3 ± 13.5 (mean ± SD); p < 0.001) and 6 hours (2.1 ± 2.7 versus 23.7 ± 12.9; p < 0.001) but not 24 hours (1.5 ± 1.3 versus 4.9 ± 6.6; p = 0.35) post-operatively. Predominant pain behavior was ‘writhe’ (flank contraction) in contrast to ‘twitch,’‘back arch,’ and ‘stagger/fall’ reported as most common pain indicators in other rat strains. BUP rats had greater mean adhesion incidence (2.4 ± 1.7 versus 1.4 ± 1.8; p < 0.03) and severity (90%³Gr.2 versus 65% of controls; p < 0.05). The BUP protocol appeared to provide effective analgesia for at least 24 hours post-operatively. Strain of rat may affect pain related behavior. BUP should be used with caution after abdominal surgical procedures having high risk of POA formation.