Abstract
The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.
Highlights
Pain generated from operation or inflammation is an important clinical concern
We have demonstrated that SN can alleviate acute pain, neuropathic pain and chronic inflammatory pain arising from rheumatoid arthritis, without introducing tolerance or observable side effects (Gao et al, 2013, 2014, 2015)
We have shown that SN could enhance the analgesic potency of ligustrazine (LGZ, known as Tetramethylpyrazine, the active substance extracted from plant Ligusticum chuanxiong Hort), which is effective on acute inflammatory pain (Liang et al, 2004), and pain after traumatic injury (Gao et al, 2019a)
Summary
Pain generated from operation or inflammation is an important clinical concern. Less than half of patients report adequate postoperative pain relief (Chou et al, 2016) following operation, and up to 60% of patients with inflammatory rheumatic diseases experience persistent pain left to be treated (Häuser and Fitzcharles, 2017). Undermanaged pain prevents recovery and induces physical and mental impairments. Antinociceptive Effects of Sinomenine Combinations (Breivik et al, 2006; Langley, 2011). When left untreated, the acute pain may undergo a “chronification” process to produce treatment-resistant pain, leading to a tremendous reduction in quality of life (Breivik et al, 2006). Finding effective analgesic methods has become a pressing challenge
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