Antinociceptive Activity of a Synthetic Curcuminoid Analogue, 2,6‐bis‐(4‐hydroxy‐3‐methoxybenzylidene)cyclohexanone, on Nociception‐induced Models in Mice

Abstract

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 ID 50 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 ID 50 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 ID 50 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.

TRPA1 receptor is upregulated in human oral lichen planus

“…Although no direct link has been established, literature data could eventually suggest a possible implication of TRPA1 in OLP: (i) plant‐derived TRPA1 agonists such as cinnemaldehyde can cause lichenoid (OLP‐like) lesions (Schlosser, ; Behzad et al , ); (ii) avoiding spicy foods and mint or cinnamon flavored oral hygiene products can alleviate OLP (Schlosser, ; Olson et al , ); and (iii) anti‐inflammatory and nociceptive curcuminoids used in OLP therapy may rapidly desensitize TRPA1 (Leamy et al , ; Ming‐Tatt et al , ; Olson et al , ).…”

Antinociceptive Activity of Asiaticoside in Mouse Models of Induced Nociception

“…The acetic acid-induced abdominal constriction or writhing assay employed in this study has been utilized as a standard assay that explores the possible peripheral antinociceptive activities of new drugs and compounds from natural sources. In principle, acetic acid acts directly by activating the nociceptors or indirectly by triggering the release of autacoid mediators in the event of an inflammation [27]. A single dose of acetic acid given intraperitoneally can aggravate the serous membrane inside the peritoneal cavity causing further tissue damage, an event which is manifested in the form of abnormal physical response like writhing [28].…”

“…A full writhing is characterized by the elongation of the abdomen followed by stretching of at least one or both hind legs. The inhibition of abdominal constriction was calculated by the following formula: Hot plate-induced nociception Heat-induced nociception was conducted as described by [27], with modifications. A total of 36 mice (6 mice in each group) were preselected 1 day before the experiment.…”

Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin fromNaja naja atra

“…In the formalin test, mice were subcutaneously injected 20  μ L 1.5% formaldehyde into the right hind paw. Then, time spent in licking the injected paw, divided into phase 1 (0–5 min) and phase 2 (15–30 min), was recorded [13, 27, 28]. …”