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This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID50 of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID50 of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID50 of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators. [ABSTRACT FROM AUTHOR]

The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K channel pathway possibly participated in the antinociceptive action induced by FKB. [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]

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]