The Involvement of l-Arginine-Nitric Oxide-cGMP-ATP-Sensitive K+ Channel Pathway in Antinociception of BBHC, a Novel Diarylpentanoid Analogue, in Mice Model

The present study focuses on the possible involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperitoneal pre-treatment of l-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K+ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC’s antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p < 0.05). Altogether, these findings suggest that the systemic administration of BBHC is able to establish a significant antinociceptive effect in a mice model of chemically induced pain. BBHC’s antinociception is shown to be mediated by the involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway, without any potential sedative or muscle relaxant concerns.

Analgesic, anti-inflammatory and antipyretic activities of ethanol extract of Annona senegalensis leaves in experimental animal models

Background: This study was carried out to establish the analgesic, anti-inflammatory and antipyretic effects of the ethanol extract of Anonna senegalensis leaves in experimental animals.Methods: The analgesic activity was measured using the abdominal constriction and tail flick tests. The anti-inflammatory activity was performed using xylene and egg-albumen paw induced tests, while the antipyretic activity was measured using brewer’s yeast and 2, 4 dinitrophenol induced pyrexia tests, respectively.Results: The leaf extract at all doses used exhibited significant (p<0.05) analgesic, anti-inflammatory and antipyretic activities.Conclusions: Results show that ethanol leaf extract of Anonna senegalensis possess therapeutic potential against pains and feverish conditions, supporting the claims of its this plant as remedy for similar ailments.

The Effect of Single or Multiple Doses of Grapefruit Juice on the Analgesic Effect of Ibuprofen in Mice

Grapefruit juice (GFJ) is a rich source of nutritional compounds but has been shown to alter the concentrations of several clinically useful drugs. Ibuprofen is a commonly used over-the counter-drug. Aim: This study aims to examine the effect of a single or multiple dose of GFJ on the analgesic effect of ibuprofen. Methodology: CD1 male mice were randomly distributed into four equal groups (n=9, each). The first group served as a control, the second group was given ibuprofen (100 mg/Kg) by oral gavage, the third group was given a single dose of GFJ (10 mg/Kg) by oral gavage followed by ibuprofen, and the fourth group was given a single dose of GFJ for five days and on the fifth day was given ibuprofen. The analgesic effect was tested using two methods with different mechanisms: thermal (hot plate) and chemical (acetic acid-induced abdominal constriction) pharmacologic stimuli models. Results: Both GFJ dosing regimen significantly increased the duration of abdominal constriction test when compared with ibuprofen group and did not exert any significant effect on the hot plate effect. This suggest that GFJ may affect the peripherally modulated analgesic effect of ibuprofen. Conclusion: The observed effect of GFJ on ibuprofen analgesic effect warrants further studies on their impact and clinical significance on humans.

The struggle with rheumatism through Dracunculus vulgaris Schott: In the light of ethnobotanical information.

Background: The fruits with the seeds of Dracunculus vulgaris Schott. (Araceae) are used against inflammatory diseases in Turkey. Objective: Present study was designed to justify this folkloric usage type of the plant. Therefore, the aim of this study is to investigate the anti-inflammatory activity of D. vulgaris. Methods: Petroleum ether, ethyl acetate and methanol extracts were prepared from the fruits, successively. Carrageenan-, serotonin-, and prostaglandin E2-induced hind paw edema; acetic acid–induced capillary permeability and 12-O-tetradecanoyl-phorbol-13-acetate–induced mouse ear edema models were used to assess the antiinflammatory activity of the extracts. The analgesic activity was experienced by using p-benzoquinone-induced abdominal constriction test. Results: The petroleum ether extract displayed the highest activities in all of the used test models compared with the control group. Therefore, the constituents of this extract were determined by using gas chromatography–mass spectroscopy (GC–MS). Linoleic acid was found to be major constituent of the petroleum ether extract of D. vulgaris. Conclusion: This study has provided some justification for the folkloric use of the plant.

THE ADDITIVITY ANTINOCICEPTIVE INTERACTIONS BETWEEN DICLOFENAC AND THE DERRIS SCANDENS EXTRACT DRUG IN MICE.

Objective: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. The objective was to determine the effects of coadministered diclofenac and the Derris scandens extract drug.Methods: Acetic acid-induced abdominal constriction test in mice was used to determine the type of interaction between components. The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of diclofenac with the D. scandens extract drug. The ED50 was compared to the theoretical additive ED50 calculated from the ED50 of diclofenac and of the D. scandens extract drug alone.Results: Diclofenac and the D. scandens extract drug dose‐dependently and significantly reduced the abdominal writhing. The combination was the additive effect, the experimental ED50 being smaller than the theoretically calculated ED50. Interaction index of the combination was 0.89.Conclusion: The present study demonstrates the additivity antinociceptive interactions between diclofenac and the D. scandens extract drug and may be used as a combination analgesic in the treatment of pain conditions.

THE ADDITIVITY ANTINOCICEPTIVE INTERACTIONS BETWEEN DICLOFENAC AND THE DERRIS SCANDENS EXTRACT DRUG IN MICE.

Objective: Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. The objective was to determine the effects of coadministered diclofenac and the Derris scandens extract drug.Methods: Acetic acid-induced abdominal constriction test in mice was used to determine the type of interaction between components. The effective dose that produced 50% antinociception (ED50) was calculated from the log dose-response curves of fixed ratio combinations of diclofenac with the D. scandens extract drug. The ED50 was compared to the theoretical additive ED50 calculated from the ED50 of diclofenac and of the D. scandens extract drug alone.Results: Diclofenac and the D. scandens extract drug dose‐dependently and significantly reduced the abdominal writhing. The combination was the additive effect, the experimental ED50 being smaller than the theoretically calculated ED50. Interaction index of the combination was 0.89.Conclusion: The present study demonstrates the additivity antinociceptive interactions between diclofenac and the D. scandens extract drug and may be used as a combination analgesic in the treatment of pain conditions.

Evidence for the absence of visceral pain in C57BL6/N mice subjected to therapeutically relevant O3/O2-pneumoperitoneum

Each different gas that is used to induce a pneumoperitoneum (PP) exhibits individual effects within the peritoneal cavity. This might include adverse effects such as pain and/or inflammatory reactions. The acute effects of ozonized oxygen (O3/O2), a highly oxidative gas mixture, after being insufflated into the peritoneal cavity are analysed in this study. Using the abdominal constriction response (‘writhing’) assay of chemical nociception in C57BL6/N mice, O3/O2-PP was found not to be associated with visible pain responses and did not alter the c-fos expression in the spinal cord. In addition, mRNA expression levels of the pro-inflammatory cytokines, interleukin (IL)-1β and IL-6, were found unaltered in the spleen 2 h after insufflation. In conclusion, O3/O2-PP is free of adverse pain and does not trigger inflammatory immune responses.

Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction

ABSTRACT Geissospermum vellosii (Pao pereira) is a Brazilian tree whose stem barks are rich in indole alkaloids that present intense anticholinesterase activity. The present study evaluated the effects of a stem bark fraction (PPAC fraction) and ethanolic extract (EE) of Pao pereira in classic murine models of inflammation and pain. The EE and PPAC fraction, both at a dose of 30 mg/kg, significantly reduced mice abdominal constriction induced by acetic acid by 34.8% and 47.5%, respectively. In the formalin test, EE (30 mg/kg) and PPAC fraction (30 and 60 mg/kg) inhibited only the second phase, by 82.8%, 84.9% and 100%, respectively. Compared with indomethacin, similar doses of EE or PPAC fraction were approximately twice as effective in causing antinociception. PPAC fraction was not effective in the hot plate test but reduced the inflammatory response at the second (50.6%) and third (57.8%) hours of rat paw edema induced by carrageenan. Antihyperalgesic activity was observed within 30 min with a peak at 2 h (60.1%). These results demonstrate that compounds in PPAC fraction have anti-inflammatory and antinociceptive activity by a mechanism apparently unrelated to the opioid system. Regardless of similar responses to indomethacin, the effects of PPAC fraction are mainly attributed to acetylcholine actions.

Mechanisms of α-Mangostin-Induced Antinociception in a Rodent Model

Objective: Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn. Methods: Male mice/rats ( n = 6/group) were used in this between-group study. To determine α-mangostin’s antinociceptive profile, animals were given α-mangostin orally (3, 30, or 100 mg/kg) 60 min before the start of the abdominal constriction or formalin tests. In the hot plate test, the noxious stimulus was applied before and 60, 90, 120, 150, 180, and 210 min after treatment with test solutions. Positive controls received 100 mg/kg acetylsalicylic acid (ASA; oral) or 5 mg/kg morphine (intraperitoneal injection) for the abdominal constriction and hot plate tests, respectively, and either ASA or morphine for the formalin test. Negative controls received vehicle only. To explore α-mangostin’s mechanisms of action, we performed (i) the hot plate test with naloxone (5 mg/kg) pretreatment to verify involvement of opioid receptors; (ii) the abdominal constriction test with 20 mg/kg l-arginine, NG-nitro-l-arginine methyl esters (l-NAME), methylene blue (MB), l-arginine plus l-NAME, or l-arginine plus MB or 10 mg/kg glibenclamide pretreatment to verify involvement of the l-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) and K+-ATP pathways; and (iii) the paw-licking test using capsaicin (1.6 μg capsaicin/paw), glutamate (10 μmol glutamate/paw), or phorbol 12-myristate 13-acetate (PMA; 0.05 µg/paw) to verify involvement of vanilloid receptors, the glutamatergic system, and protein kinase C (PKC). Results: α-mangostin significantly inhibited nociception ( p < .05) in all models. Only naloxone, l-arginine, methylene blue, PMA, and glibenclamide affected α-mangostin antinociception significantly ( p < .05). Conclusion: α-mangostin exhibits peripheral and central antinociception through modulation of opioid and vanilloid receptors, the glutamatergic system, and the l-arginine/NO/cGMP/PKC/K+-ATP pathways.