Impact of Opioid and Nonopioid Drugs on Postsurgical Pain Management in the Rat

Abstract

Aim. Nonsteroidal anti-inflammatory drugs or opioids are commonly used to control surgical pain following veterinary and clinical procedures. This study evaluated the efficacy of postoperative ketorolac or buprenorphine following abdominal surgery. Main Methods. Mean arterial pressure (MAP), heart rate, animal activity, corticosterone levels, and a nociceptive sensitivity assay were used to evaluate 18 adult male Sprague-Dawley rats which underwent aortic artery occlusion for implantation of a radiotelemetry device. The animals were treated postoperatively with intraperitoneal injections of vehicle, ketorolac (10 mg/kg), or buprenorphine (0.06 mg/kg) every 8 hours for 3 days. Key Findings. There were no consistent significant changes in any of the telemetry parameters after treatment with ketorolac compared with no saline treatment with the exception of increased MAP in the buprenorphine group during the first 48 hours when compared with other treatment groups. There was a sustained increase in fecal corticosterone levels from baseline on days 2–7 with buprenorphine compared with vehicle- or ketorolac-treated animals. All treatment conditions displayed reduced paw withdrawal thresholds (PWTs) from day 1 to day 21 following surgery. Compared with the vehicle treatment group, buprenorphine-treated animals exhibited significantly lower PWT levels from day 4 to 14 days. Significance. Given the prolonged increase in fecal corticosterone levels and pronounced changes in tactile hyperalgesia behavior in rodents subjected to buprenorphine treatment, these data suggest that ketorolac may be superior to buprenorphine for the treatment of postprocedure pain behavior in rodents.

Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats

“…Furthermore, these DAMPs, including HSP90 and fibronectin, may also mediate sustained allodynia with morphine-induced persistent sensitization. As opioids also induce persistent sensitization in other pain models, including inflammatory, postoperative, and spinal cord injury-induced pain (Ellis et al, 2016; Loram et al, 2012; Wilson et al, 2016), it remains to be determined whether DAMP signaling also plays a similar role to that described herein. As neuropathic pain is often intractable to current therapies, targeting DAMP signaling may be a novel strategy to alleviate the enormous burden of pain.…”

“…Such alterations in glutamate homeostasis can lead to excitotoxic release of DAMPs, as well as ATP release from glial cells (Liu et al, 2006; Queiroz et al, 1999). Furthermore, activation of P2X7R can induce release of ATP and reactive oxygen species, while the HMGB1 is also released as a consequence of inflammasome activation (Ficker et al, 2014; Lamkanfi et al, 2010; Suadicani et al, 2006). Therefore, the inflammasome may remain activated due to a positive feedback loop, wherein the initial amplified release of IL-1β after morphine administration creates cellular stress and release of DAMPs that signal back at TLR4 and P2X7R.…”

In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti‐inflammatory effects

“…Because the end‐point of these studies involved the vasculature, systemic administration was used to provide appropriate bioavailability. The bioavailability of ketorolac is widely known (43,44), and the dosing regimen was adopted accordingly…”

Effect of nalbuphine on patient controlled intravenous analgesia after radical resection of colon cancer

“…At present, morphine, fentanyl, sufentanyl and other opioids are commonly used drugs for postoperative analgesia after laparoscopic surgery, all of which are μ receptor agonists. The limited use of these drugs in clinical practice is due to their adverse reactions such as respiratory depression, nausea and vomiting, excessive sedation and dysuria (6). Nalbuphine is a new kind of analgesic, which belongs to opioids.…”