METHODS: The antinociceptive potential of orally administered PECN (100, 250, 500 mg/kg) was studied using the abdominal constriction-, hot plate- and formalin-induced paw licking-test in mice (n = 6). The effect of PECN on locomotor activity was also evaluated using the rota rod assay. The role of opioid receptors was determined by pre-challenging 500 mg/kg PECN (p.o.) with antagonist of opioid receptor subtypes, namely β-funaltrexamine (β-FNA; 10 mg/kg; a μ-opioid antagonist), naltrindole (NALT; 1 mg/kg; a δ-opioid antagonist) or nor-binaltorphimine (nor-BNI; 1 mg/kg; a κ-opioid antagonist) followed by subjection to the abdominal constriction test. In addition, the role of L-arg/NO/cGMP pathway was determined by prechallenging 500 mg/kg PECN (p.o.) with L-arg (20 mg/kg; a NO precursor), 1H-[1, 2, 4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 2 mg/kg; a specific soluble guanylyl cyclase inhibitor), or the combinations thereof (L-arg + ODQ) for 5 mins before subjection to the abdominal constriction test. PECN was also subjected to phytoconstituents analyses.

RESULTS: PECN significantly (p  0.05) affect the locomotor activity of treated mice. The antinociceptive activity of PECN was significantly (p  0.05) affected by ODQ. HPLC analysis revealed the presence of at least cinnamic acid in PECN.

MATERIALS AND METHODS: The MEZZ was prepared by macerating oven-dried (50 degrees C) powdered rhizomes (1.2 kg) of Z. zerumbet in 80% methanol in a ratio of 1:20 (w/v) for 48 h. The supernatant was collected, filtered and evaporated to dryness under reduced pressure (50 degrees C) yielding approximately 21.0 g of the crude dried extract. The crude dried extract was stored at -20 degrees C prior to use and was dissolved in normal saline (0.9% NaCl) immediately before administration at concentrations required to produce doses of 25, 50 and 100 mg/kg.

RESULTS: All dosages of MEZZ showed significant (p < 0.05) antiedema activity when assessed using the carrageenan-induced paw edema test and the cotton-pellet-induced granuloma test. The MEZZ exhibited significant (p < 0.05) antinociceptive activity when assessed by the writhing, hot plate and formalin tests. Pretreatment with naloxone (5 mg/kg) significantly decreased the latency of discomfort produced by the 100 mg/kg dose of MEZZ in the hot plate test.

AIM OF THE STUDY: To explore the antinociceptive (acute pain) and anti-neuropathic (chronic pain) activities of Lotus corniculatus leaves essential oil (LCEO) in addition to uncovering the possible mechanisms of antinociception.

MATERIALS AND METHODS: LCEO as well as the pure oleanolic acid (OA) compound, were assayed for their effects on acute (formalin induced paw licking test or FIPT) and chronic (cervical contusion injury models on the fifth cervical vertebra or CCS; 14-day intervals) pain. The possible involvements of NO-cGMP-K+ channel, TRPV, dopamine, cannabinoid, PPAR, adrenergic, and opioid mechanisms in the antinociceptive activity of LCEO have studied by formalin test. The levels of p53 and inflammatory markers were measured using a streptavidin biotin immune peroxidase complex and ELISA methods, respectively.

RESULTS: The LCEO and OA exerted antinociceptive activity in the first-phase of FIPT. Pretreatment with antagonists of TRPV1, dopamine D2, cannabinoid type1 and 2, and NO-cGMP-K+ channel blockers (glibenclamide, L-NAME and methylene blue) attenuated the antinociceptive effect of LCEO in FIPT. In addition, LCEO and OA meaningfully reduced hyperalgesia (days 6-14) and mechanical allodynia (days 2-14) in the CCS model. LCEO suppressed the apoptotic marker (p53) in CCS model and also ameliorated IL-2, TNF-α, and IL-1 in the spinal cord.

METHODS: Formalin-induced paw licking model was used to assess the anti-nociceptive activity of CMEO and its major constituent, terpinolene (TP). The anti-nociceptive activity of these compounds was determined by investigating the roles of various non-opioid and NO-cGMP-K+ channels. Additionally, the anti-neuropathic potential of CMEO and TP was determined using cervical spinal cord contusion/CCS technique.

RESULTS: The CMEO exerted significant anti-nociceptive activity with a remarkable activity seen in the second phase of formalin-induced paw licking model and this activity were remarkably reversed by pre-treatment of naloxone (an opioid antagonist). Pretreatment with several types of NO-cGMP-potassium channel pathway meaningfully reversed the anti-nociceptive potential of CMEO in phase II of formalin model. Moreover, pre-treatment with several antagonists of non-opioid receptors revealed that only the antagonist of TRPV-1, serotonin type 3, 5-HT2, α2 adrenergic, and CB1 receptors (capsaicin, ondansetron, ketanserin, yohimbine, and SR141716A, respectively) reversed CMEO anti-nociception. CMEO and TP also remarkably reversed hyperalgesia and mechanical allodynia in the CCS technique.