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Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV1, glutamate, and opioid receptors. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although bradykinin is a potent algogenic peptide, the roles of this peptide and kinin receptors in cancer pain are unclear. Aims: The present study was conducted to clarify whether kinin B1 and B2 receptors would be involved in pain using a mouse model of skin cancer pain. Methods: B16-BL6 melanoma cells were inoculated into the hind paw of C57BL/6 mice. Licking, an index of spontaneous pain, allodynia and hyperalgesia were observed. Expression of kinin receptor mRNAs was analyzed with reverse transcription and polymerase chain reaction. The contents of kininogen and bradykinin-related peptides were assayed with Western blotting and enzyme immunoassay, respectively. Results: Melanoma inoculation induced spontaneous licking of the melanoma-bearing paw from day 18 post-inoculation, which was inhibited by local injections of B1 and B2 receptor antagonists. Allodynia was briefly attenuated by B2, but not B1 antagonist and hyperalgesia was not inhibited by either B1 or B2 antagonist. Local injections of B1 and B2 receptor agonists increased licking behavior in melanoma-bearing, but not healthy, paw. The expression of kinin B1, but not B2, receptor mRNA was markedly increased in the L4/5 dorsal root ganglia on the melanoma-bearing side. Melanoma cells expressed B1 and B2 receptors and kininogen. The content of bradykinin and related peptides was increased in the melanoma mass as compared with healthy skin. Conclusions: Bradykinin and related peptides released from melanoma cells may cause spontaneous pain and allodynia in the melanoma-bearing paw, in which B1 and B2 receptors on primary afferent and melanoma cells may have different roles. [Copyright &y& Elsevier]

Abstract: The present study was conducted to determine whether bradykinin would affect the secretion and expression of endothelin-1 (ET-1) in B16-BL6 melanoma cells. Bradykinin administered to cultured melanoma cells increased preproET-1 mRNA level and the secretion of ET-1. Although kinin B1 and B2 receptor mRNAs are expressed in the melanoma cells, the increase of preproET-1 mRNA expression and the secretion of ET-1 were inhibited by kinin B2, but not by B1, receptor antagonist. These results suggest that bradykinin regulates the secretion and biosynthesis of ET-1 through kinin B2 receptor in tumor cells, especially melanoma cells. [Copyright &y& Elsevier]

Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals. [ABSTRACT FROM AUTHOR]

Abstract: The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall–Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening. [Copyright &y& Elsevier]