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Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

ABSTRACT: This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-?, IL-6, VEGF, and IL-1?) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-?, IL-6, and IL-1? while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

SUBMITTER: Wu MH

PROVIDER: S-EPMC5653328 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

Wu Meng-Huang MH Shih Ming-Hung MH Hsu Wei-Bin WB Dubey Navneet Kumar NK Lee Wen-Fu WF Lin Tsai-Yu TY Hsieh Meng-Yow MY Chen Chin-Fu CF Peng Kuo-Ti KT Huang Tsung-Jen TJ Shi Chung-Sheng CS Guo Ren-Shyang RS Cai Chang-Jhih CJ Chung Chiu-Yen CY Wong Chung-Hang CH

PloS one 20171023 10

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) ...[more]

PMID: 29059223

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Project description:Background and Objectives: This study aimed to identify the analgesic properties of immature Rubus occidentalis extract (iROE) using a postoperative-pain rat model. We also aimed to compare the analgesic effects of iROE to those of mature R. occidentalis extract (mROE) and examine the proinflammatory cytokine response and associated underlying mechanisms. Materials and Methods: In adult male Sprague Dawley rats, acute postoperative pain was induced through plantar hind-paw incisions. After the plantar incisions were made, the rats were intraperitoneally administered with normal saline or various doses of iROE and mROE to investigate and compare the analgesic effects of iROE and mROE. The mechanisms underlying iROE-induced analgesia were investigated via post-incisional administration of yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine, followed by iROE. Mechanical withdrawal threshold (MWT) evaluations with von Frey filaments were carried out at different time points. Serum levels of tumor necrosis factor α, interleukin (IL)-1β, and IL-6 were measured to assess inflammatory responses. Multivariate analysis of variance (MANOVA) and linear mixed-effects model (LMEM) analysis were used to analyze the analgesic effect data. Results: The MWTs demonstrated significant increases in iROE in a dose-dependent manner up to 2 h after the plantar incisions were made. An LMEM analysis demonstrated that iROE yielded a significantly greater analgesic effect than mROE, but there was no significant difference between the two according to MANOVA. Dexmedetomidine enhanced the MWT-confirmed iROE response, while yohimbine and naloxone diminished it. Administration of iROE significantly attenuated the post-incisional increases in serum IL-1β and IL-6 levels. Conclusions: The iROE demonstrated analgesic and anti-inflammatory effects in a rat model of incisional pain, which were more pronounced than those associated with mROE. The analgesic activity of iROE may be associated with α2-adrenergic and opioid receptors.

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Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

Publications

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

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