[Carbon Monoxide and Pain Regulation: A Review].

Carbon monoxide (CO) is an endogenous gasotransmitter produced by the degradation of heme in the presence of heme oxygenase (HO) in mammals. It has been demonstrated that CO participates in a variety of physiological activities and pathological processes, and is closely related to cell protection and homeostasis maintenance in organ tissues. It has been shown by a growing number of studies that CO may play a regulatory and interventional role in the process of the occurrence and development of pain through a variety of mechanisms of action. However, its mechanism of action is still not fully understood and the uncontrollable factors concerning CO administration also placed considerable limitation to its application. This paper reviews the potential targets and pathways of CO in pain regulation and discusses the challenges and opportunities in the clinical application of CO in order to provide suggestions for further exploration and development of CO analgesics.

Anti-inflammatory and anti-hyperalgesic effects of milnacipran in inflamed rats: involvement of myeloperoxidase activity, cytokines and oxidative/nitrosative stress.

BACKGROUND: Many injuries cause pain and inflammation, which are one of the major challenges for physicians. In this study, the analgesic and the anti-inflammatory effects of milnacipran were investigated on carrageenan-induced nociception and inflammation in male rats. METHODS: Pain and inflammation were induced by injection of λ-carrageenan (1% v/v) into the hind paw. Indomethacin (10 mg/kg: ip) or milnacipran (10, 20 and 40 mg/kg: ip) were administered 30 min before carrageenan. Analgesia and inflammation were measured by hot plate and plethysmometer. Finally, lipid peroxidation, tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1ß), Interleukin 6 (IL-6), myeloperoxidase (MPO) activity, nitric oxide (NO) and total antioxidant capacity (TAC) status evaluated in the hind paw tissue. RESULTS: The results showed that carrageenan caused hyperalgesia and inflammation in the hind paw tissue. Milnacipran (20 and 40 mg/kg) significantly and dose-dependently attenuated (65 ± 3.2%; p ≤0.01 and 42 ± 6.2%; p ≤ 0.001, respectively) carrageenan-induced inflammation and significantly increased (p ≤ 0.001) nociception threshold. Also, milnacipran (20 and 40 mg/kg) significantly suppressed levels of malondialdehyde (MDA), NO (p ≤ 0.05), MPO activity, TNF-α, IL-1ß and IL-6 (p ≤ 0.001) following carrageenan injection. Additionally, milnacipran (10, 20 and 40 mg/kg) significantly augmented (p ≤ 0.05) TAC status following carrageenan in the hind paw tissue. CONCLUSION: In the present study, milnacipran showed anti-nociceptive and anti-inflammatory effects on carrageenan-induced hyperalgesia and inflammation in a dose-dependent manner. Milnacipran reduced inflammatory edema and increased the paw withdrawal threshold probably through suppression of MDA, NO, TNF-α, IL-1ß, IL-6 and MPO activity, and increase of TAC status in the hind paw tissue. Therefore, milnacipran holds important potential as an anti-inflammatory and anti-nociceptive drug. Although, further clinical trials to confirm this issue, is required.

Role of nociceptin/orphanin FQ opioid peptide receptor in pain modulation / 国际药学研究杂志

Pain is not only a common syndrome in clinic,but also a disease harming people′s health and quality of life. Dis?covery of potent and low-or non-addictive analgesic agent is a great challenge and our expectation. Nociceptin/orphanin FQ opioid pep?tide (NOP)receptor,the fourth member of the opioid receptor family,was discovered in 1994. Growing evidence has revealed that NOP receptor plays an important role in pain transduction and modulation and becomes a potential target for novel analgesics develop?ment. This review focuses on the progresses in exploring the biological characteristics of NOP receptor and its complex role in pain modulation,as well as the discovery of novel analgesic agents targeting NOP receptor,which provides reference for understanding the mechanisms of pain and analgesia and finding ideal analgesics.

Role of nociceptin/orphanin FQ opioid peptide receptor in pain modulation / 国际药学研究杂志

Pain is not only a common syndrome in clinic, but also a disease harming people’s health and quality of life. Discovery of potent and low-or non-addictive analgesic agent is a great challenge and our expectation. Nociceptin/orphanin FQ opioid peptide (NOP)receptor, the fourth member of the opioid receptor family, was discovered in 1994. Growing evidence has revealed that NOP receptor plays an important role in pain transduction and modulation and becomes a potential target for novel analgesics development. This review focuses on the progresses in exploring the biological characteristics of NOP receptor and its complex role in pain modulation, as well as the discovery of novel analgesic agents targeting NOP receptor, which provides reference for understanding the mechanisms of pain and analgesia and finding ideal analgesics.