Analgesic effects of stem bark extracts of Trichilia monadelpha (Thonn.) JJ De Wilde

Abstract

Objectives: Various parts of Trichilia monadelpha (Thonn) JJ De Wilde (Fam. Meliaceae) are used in Ghanaian traditional medicine for the treatment of painful and inflammatory conditions. The present study examined the analgesic properties of the petroleum ether (PEE), ethyl acetate (EAE), and the hydro-ethanolic (HAE) extract of the stem bark of the plant in murine models.

Materials and methods: PEE, EAE, and HAE were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models. The possible mechanisms of the antinociceptive action were also examined with various antagonists in the formalin test.

Results: HAE, EAE, and PEE, each at doses of 10-100 mg/kg orally, and the positive controls (morphine and diclofenac) elicited significant dose-dependent antinociceptive activity in the chemical (acetic acid abdominal writhing and formalin tests), thermal (hot plate test), and mechanical (Randall-Selitto paw pressure test) pain models in rodents. The antinociceptive effect of HAE was partly or wholly reversed by systemic administration of atropine, naloxone, and glibenclamide. The antinociceptive effects of EAE and PEE were inhibited by atropine.

Conclusion: The extracts HAE, EAE, and PEE caused dose-related antinociception in chemical, thermal, and mechanical models of pain in animals. The mechanism of action of HAE involves an interaction with muscarinic cholinergic, adenosinergic, opioidergic pathways, and ATP-sensitive K+ channels while that of EAE and PEE involve the muscarinic cholinergic system.

Keywords: Formalin test; hot plate; pain; randall-selitto test; writhing test.

Figure 1

Effect of HAE (10–100 mg/kg), EAE (10–100 mg/kg), PEE (10–100 mg/kg) and diclofenac (3-30 mg/kg) on the time course curves (a, c, e, g) and the total nociceptive score (calc. as AUCs) (b, d, f, h) of acetic acid-induced writhing in mice. Nociceptive scores are shown in 5-minute time blocks up to 30 min for the time course curves. Data are presented as mean ± SEM (n = 5). The lower and upper margins of the boxes (b, d, f, h) represent the 25^th and 75^th percentiles, with the extended arms representing the 10^th and 90^th percentiles, respectively. The median is shown as the horizontal line within the box.*P < 0.05, **P < 0.01, ***P < 0.001 compared to the control group (ctrl) (two-way repeated measures ANOVA followed by Bonferroni's post hoc). ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001 compared to the control group (ctrl) (one-way ANOVA followed by Newman–Keuls post hoc)

Figure 2

Effect of HAE (10–100 mg/kg), EAE (10–100 mg/kg), PEE (10–100 mg/kg) and morphine (0.3-3 mg/kg) on the time course curves (a, c, e) and the total nociceptive score (calc. as AUCs) (b, d, f) of formalin-induced nociception in mice. Nociceptive scores are shown in 5-minute time blocks up to 60 min for the time course curves. Data are presented as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 compared to the control group (ctrl) (two-way repeated measures ANOVA followed by Bonferroni's post hoc). ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001 compared to the control group (ctrl) (one-way ANOVA followed by Newman–Keuls post hoc)

Figure 3

Effect of HAE (10–100 mg/kg), EAE (10–100 mg/kg), PEE (10–100 mg/kg) and morphine (0.3-3 mg/kg) on the time course curves (a, c, e) and the total antinociceptive effect (calc. as AUCs) (b, c, f) in the hot plate test in mice. Data are presented as mean ± S.E.M. (n = 5). The lower and upper margins of the boxes (b, d, f) represent the 25^th and 75^th percentiles, with the extended arms representing the 10^th and 90^th percentiles, respectively. The median is shown as the horizontal line within the box..*P < 0.05, **P < 0.01, ***P < 0.001 compared to the control group (ctrl) (two-way repeated measures ANOVA followed by Bonferroni's post hoc). ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001 compared to the control group (ctrl) (one-way ANOVA followed by Newman–Keuls post hoc).

Figure 4

Effect of HAE (10–100 mg/kg), EAE (10–100 mg/kg), PEE (10–100 mg/kg) and morphine (0.3-3 mg/kg) on the time course curves (a, c, e, g) and the total nociceptive score (AUCs) (b, d, f, h) of carrageenan-induced mechanical hyperalgesia in rats. Data are presented as mean ± S.E.M. (n = 5). The lower and upper margins of the boxes (b, d, f, h) represent the 25^th and 75^th percentiles, with the extended arms representing the 10^th and 90^th percentiles, respectively. The median is shown as the horizontal line within the box.*P < 0.05, **P < 0.01, ***P < 0.001 compared to the control group (ctrl) (two-way repeated measures ANOVA followed by Bonferroni's post hoc). ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001 compared to the control group (ctrl) (one-way ANOVA followed by Newman–Keuls post hoc).

Figure 5

Effects of pretreatment of rats with atropine (5 mg/kg, i.p.), naloxone (2 mg/kg, i.p.), theophylline (10 mg/kg, i.p.); glibenclamide (8 mg/kg, p.o.) and yohimbine (3 mg/kg, p.o.) on the antinociceptive effects of (a) HAE (100 mg/kg, p.o.), (b) EAE (100 mg/kg, p.o.), (c) PEE (100 mg/kg, p.o.) or (d) morphine (1 mg/kg, i.p.) in the formalin test. Each column represents mean ± S.E.M. (n = 5). *P < 0.05; **P < 0.001; ***P < 0.0001 compared to the vehicle-treated group. (two-way ANOVA followed by Bonferroni's post hoc test). ^††P < 0.01; ^†††P < 0.0001 compared to the HAE-, EAE- or PEE-treated group (one-way ANOVA followed by Newman=Keuls post hoc).