Antihypernociceptive effects of Petersianthus macrocarpus stem bark on neuropathic pain induced by chronic constriction injury in rats.

Petersianthus macrocarpus (Lecythidaceae) stem bark is traditionally used in West and Central Africa for the treatment of boils and pain. The present study examined the chemical composition of the aqueous and methanolic stem bark extracts of P. macrocarpus by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) . Their antinociceptive effect was evaluated using chronic constriction injury (CCI)-induced neuropathic pain in a rat model. On the ninth day post-surgery, the pain perception (allodynia and hyperalgesia) of the animals was assessed after the administration of aqueous and methanolic extracts at the doses of 100 and 200 mg/kg. In addition, the effect of the extracts was evaluated on nitric oxide activity and on the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and NF-κB). The LC-ESI-MS analysis revealed the presence of ellagic acid as the major constituent in the methanol extract. Both extracts at the employed doses (100 and 200 mg/kg), significantly (p < 0.01 and p < 0.001) reduced the spontaneous pain, tactile and cold allodynia, and mechanical hyperalgesia. The methanolic extract used at the dose of 200 mg/kg significantly reduced the nitric oxide level (p < 0.001) and the gene expression levels of NF-κB (p < 0.05) and TNF-α (p < 0.01) in the brain. These data may indicate that stem bark extracts of P. macrocarpus possess a potent anti-hypernociceptive effect on CCI neuropathic pain. The inhibition of the nitric oxide pathway as well as the reduction in NF-κB and TNF-α gene expression in the brain may at least partially contribute to this effect. The results further support the use of this plant by traditional healers in pain conditions.

Antinociceptive, anti-inflammatory and antioxidant effects of Boerhavia coccinea extracts and fractions on acute and persistent inflammatory pain models.

Background Boerhavia coccinea (Nyctaginaceae) is an herbaceous plant used for the treatment of pain. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the aqueous (AEBC) and ethanol (EEBC) extracts of Boerhavia coccinea as well as the major fractions (F1, F2 and F3) from EEBC. Methods The antinociceptive effect of the extracts and fractions was evaluated using formalin test. AEBC, EEBC and F1 were selected and further evaluated acutely (24 h) and chronically (16 days) in Complete Freund's Adjuvant (CFA)-induced persistent inflammatory pain for their antihyperalgesic and anti-inflammatory effects. They were administered orally (100 and 200 mg/kg/day) from 48 h following the intraplantar injection of 100 µL of CFA. After the 16 days of chronic treatment, rats' spinal cord and brain were collected for the evaluation of oxidative stress parameters namely nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT). Results AEBC, EEBC and F1 significantly inhibited the first and second phases of the formalin-induced pain. They significantly reduced the hyperalgesia both in acute and chronic treatments. These extracts showed no acute anti-inflammatory effect. AEBC and EEBC exhibited anti-inflammatory activities after repeated administration. AEBC, EEBC and F1 significantly reduced MDA level and significantly increased SOD and catalase activities, mainly in the spinal cord. AEBC and EEBC also reduced the NO production in the spinal cord. Conclusions Boerhavia coccinea extracts and F1 possess potent antinociceptive activity which is not related to their anti-inflammatory properties. Their antioxidant effects may contribute to these activities in chronic treatment.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

BACKGROUND: Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. METHODS: The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. RESULTS: AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. CONCLUSION: AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Antihypernociceptive and antioxidant effects of Petersianthus macrocarpus stem bark extracts in rats with complete Freund's adjuvant-induced persistent inflammatory pain.

Background Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is a plant used in Cameroonian folk medicine to cure ailments such as inflammation and pain. Previous work showed that aqueous (AEPM) and methanol (MEPM) extracts from the stem bark of P. macrocarpus possess acute analgesic activities. The present study evaluates whether the same extracts could inhibit persistent hyperalgesia induced by complete Freund's adjuvant (CFA) in rats. Methods Inflammatory pain was induced by intraplantar injection of CFA into the left hind paw of Wistar rats. AEPM and MEPM were administered either acutely or chronically by the oral route at the doses of 100 and 200 mg/kg/day. The mechanical hyperalgesia was tested using an analgesimeter, while the locomotion activity at the end of experiment was evaluated with an open-field device. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were assayed in the brain and spinal cord of rats subjected to 14 days chronic treatment. Results AEPM and MEPM at both doses significantly (p<0.001) inhibited the acute and chronic mechanical hyperalgesia induced by CFA. Although not significant, both extracts increased the mobility of CFA-injected animals. AEPM significantly (p<0.01) reduced the level of nitrate at 100 mg/kg, MDA at 200 mg/kg and significantly (p<0.05) increased the SOD in the spinal cord. MEPM significantly increased the SOD content and reduced the MDA concentration in the brain but had no effect on the nitrate. Conclusions AEPM and MEPM exhibit acute and chronic antihyperalgesic activities. In addition, both extracts possess antioxidant properties that might strengthen their chronic antihyperalgesic effects.

Antinociceptive properties of the aqueous and methanol extracts of the stem bark of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous maceration from the stem barks of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is taken orally in the central Africa for the management of various ailments, including pain. AIM OF THE STUDY: This work was carried out to evaluate in mice, the antinociceptive effects of the aqueous and methanol extracts of the stem bark of P. macrocarpus. MATERIALS AND METHODS: The chemical composition of the aqueous and methanol extracts prepared as cold macerations was determined by high performance liquid chromatography coupled with mass spectrometry (LCMS). The antinociceptive effects of these extracts administered orally at the doses of 100, 200 and 400 mg/kg were evaluated using behavioral pain model induced by acetic acid, formalin, hot-plate, capsaicin and glutamate. The rotarod test was also performed at the same doses. The oral acute toxicity of both extracts was studied at the doses of 800, 1600, 3200 and 6400 mg/kg in mice. RESULT: The LCMS analysis revealed the presence of ellagic acid as the major constituent in the methanol extract. Both extracts of P. macrocarpus significantly and dose dependently reduced the time and number of writhing induced by acetic acid. They also significantly inhibited the two phases of formalin-induced pain. These effects were significantly inhibited by a pretreatment with naloxone, except for the analgesic activity of the methanol extract at the earlier phase. In addition, nociception induced by hot plate, intraplantar injection of capsaicin or glutamate was significantly inhibited by both extracts. Acute toxicity test showed no sign of toxicity. CONCLUSION: These results demonstrate that aqueous and methanol extracts of P. macrocarpus are none toxic substances with good central and peripheral antinociceptive effects that are at least partially due to the presence of ellagic acid. These extracts may induce their antinociceptive effect by interfering with opioid, capsaicin and excitatory amino acid pathways.