Effects of a Lidocaine-Loaded Poloxamer/Alginate/CaCl2 Mixture on Postoperative Pain and Adhesion in a Rat Model of Incisional Pain.
Pain and adhesion are problematic issues after surgery. Lidocaine has analgesics and anti-inflammatory properties, and poloxamer/alginate/CaCl2 (PACM) is a known antiadhesive agent. We hypothesized that the novel combination of lidocaine as chemical barrier and PACM as physical barrier would be beneficial for both postoperative pain and adhesion. The purpose of this study was to investigate the effects of lidocaine-loaded PACM in a rat model of incisional pain. Primary outcome was to evaluate between-group differences for the mechanical withdrawal threshold (MWT) measured by von Frey filament in various concentrations of lidocaine-loaded PACM applied, PACM applied, and sham-operated groups.



Male Sprague-Dawley rats were used for the postoperative pain model. After plantar incision and adhesion formation, 0.5%, 1%, 2%, and 4% lidocaine-loaded PACM, PACM only, nothing, and 4% lidocaine only were applied at the incision site in groups PL0.5, PL1, PL2, PL4, P, S, and L4, respectively. MWT using a von Frey filament and serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and high-sensitivity C-reactive protein were measured. Rats were euthanized 2 weeks after surgery, and inflammation and fibrosis were assessed with microscopy. Data were analyzed using the Kruskal-Wallis test, multivariate analysis of variance, and linear mixed-effect model. To compare MWT at each time point, analysis of variance with Bonferroni correction was used.



Multivariate analysis of variance showed that 4% lidocaine-loaded PACM significantly raised the MWT up to 6 and 8 hours after surgery compared with lidocaine-unloaded groups S and P, respectively; 2% lidocaine-loaded PACM significantly increased the MWT at 4 hours after surgery compared with groups S and C. Linear mixed-effect model showed that the MWT (estimated difference in means [95% confidence interval]) was significantly increased in groups PL2 and PL4 (6.58 [2.52-10.63], P = .002; 11.46 [7.40-15.51], P < .001, respectively) compared with group P. Inflammation and fibrosis seen on microscopic evaluation were significantly decreased in groups PL2 and PL4 compared with group S. Four percent of lidocaine only showed a significant reduction in inflammation. Serum levels of tumor necrosis factor-α, IL-1β, IL-6, and high-sensitivity C-reactive protein were decreased in lidocaine-loaded groups compared with group S or P at 1, 2, and 48 hours, and 2 weeks after surgery, respectively.



Lidocaine-loaded PACM reduced postoperative pain, and lidocaine strengthened the antiadhesive effect of PACM.
From the *Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea; †Department of Pathology, College of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; ‡Department of Anesthesiology and Pain Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; §Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea; and ‖R&D Center, Genewel Co, Ltd, Sungnam, Republic of Korea.
Geun Joo
GJ
Choi
Hyun
H
Kang
Min Eui
ME
Hong
Hwa Yong
HY
Shin
Chong Wha
CW
Baek
Yong Hun
YH
Jung
Younsuk
Y
Lee
Jeong Wook
JW
Kim
I L Kyu
ILK
Park
Wan Jin
WJ
Cho
D000464:Alginates / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001522:Behavior, Animal; D002122:Calcium Chloride / Q000008:administration & dosage*; D004195:Disease Models, Animal; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D008012:Lidocaine / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D020442:Poloxamer / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000601:surgery*; D016896:Treatment Outcome
D000464:Alginates; D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D006603:Hexuronic Acids; D020442:Poloxamer; D020723:Glucuronic Acid; D008012:Lidocaine; D002122:Calcium Chloride