quercetin and Pain

We report the design, the synthesis and the biological evaluation of the analgesic and anti-inflammatory activities of furoxanyl N-acylhydrazones (furoxanyl-NAH) by applying molecular hybridization approach. Hybrid compounds with IL-8-release inhibition capabilities were identified. Among them, furoxanyl-NAH, 17, and benzofuroxanyl-derivative, 24, together with furoxanyl-NAH derivative, 31, without IL-8 inhibition displayed both orally analgesic and anti-inflammatory activities. These hybrid derivatives do not have additional LOX- or COX-inhibition activities. For instance, LOX-inhibition by furoxanyl-NAH derivative, 42, emerged as a structural lead to develop new inhibitors. The lack of mutagenicity of the active derivatives 17, 31, and 42, allow us to propose them as candidates for further clinical studies. These results confirmed the success in the exploitation of hybridization strategy for identification of novel N-acylhydrazones (NAH) with optimized activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Cell Line; Cyclooxygenase Inhibitors; Drug Design; Female; Humans; Hydrazones; Inflammation; Interleukin-8; Lipoxygenase Inhibitors; Male; Mice; Oxadiazoles; Pain; Rats

The level of analgesia has been investigated in mice of two genotypes C57BL/6J Bl/6j and CBA/CaLac with the somatic pain caused by the formalin test after irradiation of acupuncture point E-36 by microwaves of low intensity (30-300 GHz, density of a stream of capacity of 3-10-9 B(T)/cm2) on a background entered corvitin (20 mg/kg). It is shown, that the action of these two factors causes significant analgesia with different levels: 43% in C57BL/6J Bl/6j mice and 33% in CBA/CaLac mice. The intensity of analgesia after action of microwaves and corvitin exceeds the level attained during separate use of these factors.

Topics: Acupuncture Points; Analgesia; Analgesics; Animals; Combined Modality Therapy; Flavonoids; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Microwaves; Pain; Pain Management; Pain Measurement; Species Specificity

In experiments on mice of lines C57BL/6J and CBA/CaLac, the possibility of strengthening of analgesic effect of corvitin by the action of red polarized light (PL) on the acupoint (AP) E-36 was studied. The pain behavioral response (licking of the painful area) was caused by injection of 5% formalin in hind limb (0.25 microl subcutaneously). The duration of pain response was studied before and after systemic introduction of corvitin (10 mg/kg, intraperitoneal) or joint use of corvitin and red PL (10 minute session). It is established, that after application of red PL on the antinociceptive AP E-36 in all animals an authentic strengthening of antinociceptive effect of corvitin takes place. In C57BL/6J mice, application of corvitin alone weakened the pain response by 29.7% and during combined use of red PL and corvitin, it grew up to 53.1%. Mice of line CBA/CaLac were less sensitive both to corvitin, and PL. In this line, corvitin used alone reduced the duration of pain response by 14%, and by 32.4% during combined use with red PL. Non-traumatic, without side effects, the method of influence by low-intensive PL can be recommended to patients accepting corvitin for strengthening its efficiency.

Topics: Acupuncture Points; Analgesics; Animals; Behavior, Animal; Combined Modality Therapy; Flavonoids; Light; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Pain; Pain Management; Pain Measurement; Pain Threshold; Species Specificity

Quercetin (1) is known to have both antioxidant and antinociceptive effects. However, the mechanism involved in its antinociceptive effect is not fully elucidated. Cytokines and reactive oxygen species have been implicated in the cascade of events resulting in inflammatory pain. Therefore, we evaluated the antinociceptive mechanism of 1 focusing on the role of cytokines and oxidative stress. Intraperitoneal and oral treatments with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid and phenyl-p-benzoquinone and also the second phase of formalin- and carrageenin-induced mechanical hypernociception. Compound 1 also inhibited the hypernociception induced by cytokines (e.g., TNFalpha and CXCL1), but not by inflammatory mediators that directly sensitize the nociceptor such as PGE2 and dopamine. On the other hand, 1 reduced carrageenin-induced IL-1beta production as well as carrageenin-induced decrease of reduced glutathione (GSH) levels. These results suggest that 1 exerts its analgesic effect by inhibiting pro-nociceptive cytokine production and the oxidative imbalance mediation of inflammatory pain.

Topics: Analgesics; Antioxidants; Biological Products; Cytokines; Inflammation; Molecular Structure; Oxidative Stress; Pain; Quercetin