The analgesic effects of ulinastatin either as a single agent or in combination with sufentanil: A novel therapeutic potential for postoperative pain
| Autor: | Zhong-Mou Shi, Xiao-Zhi Wu, Guo-Zhong Chen, Li-Ping Wang, Huang-Hui Wu, Fei Yang, Mei-Xiang Zhan, Chang-Lu Huang, Li Tang, Zhi-Bin Guo, Chen-Long Yang, Yi-Qing Zou |
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| Rok vydání: | 2021 |
| Předmět: |
Pain Threshold
0301 basic medicine Sufentanil medicine.medical_treatment Analgesic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Prostaglandin E2 Receptor Glycoproteins Pharmacology Analgesics Pain Postoperative business.industry Ulinastatin Rats 030104 developmental biology Nociception chemistry Opioid Hyperalgesia Anesthesia business Adjuvant 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Journal of Pharmacology. 907:174267 |
| ISSN: | 0014-2999 |
| Popis: | Ulinastatin is a broad-spectrum protease inhibitor widely used for the treatment of various inflammation-related diseases owing to its recognized excellent anti-inflammatory and cytoprotective properties. However, whether ulinastatin can relieve postoperative pain remains unclear. In this study, we evaluated the analgesic effects of ulinastatin administered either as a single agent or in combination with sufentanil in a validated preclinical rat model of postoperative pain induced by plantar incision. We found that incisional surgery on the hind paw of these rats induced sustained ipsilateral mechanical pain hypersensitivity that lasted for at least 10 days. A single intraperitoneal (i.p.) injection of ulinastatin prevented the development and reversed the maintenance of incision-induced mechanical pain hypersensitivity in a dose-dependent manner. However, ulinastatin had no effect on the baseline nociceptive threshold. Moreover, repeated i.p. injections of ulinastatin persistently attenuated incision-induced mechanical pain hypersensitivity and promoted recovery from the surgery. The rats did not develop any analgesic tolerance over the course of repeated injections of ulinastatin. A single i.p. injection of ulinastatin was also sufficient to inhibit the initiation and maintenance of incision-induced hyperalgesic priming when the rats were subsequently challenged with an ipsilateral intraplantar prostaglandin E2 injection. Furthermore, the combined administration of ulinastatin and sufentanil significantly enhanced the analgesic effect of sufentanil on postoperative pain, which involved mechanisms other than a direct influence on opioid receptors. These findings demonstrated that ulinastatin had a significant analgesic effect on postoperative pain and might be a novel pharmacotherapeutic agent for managing postoperative pain either alone or as an adjuvant. |
| Databáze: | OpenAIRE |
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