Mechanisms coupled to kinin B1 and B2 receptors have been implicated in sensory changes associate... more Mechanisms coupled to kinin B1 and B2 receptors have been implicated in sensory changes associated to various models of neuropathy. The current study aimed to investigate if kinins also participate in orofacial thermal hyperalgesia induced by constriction of the infraorbital nerve (CION), a model of trigeminal neuropathic pain which displays persistent hypersensitivity to orofacial sensory stimulation, in rats and mice. Male Swiss mice (30–35 g) or Wistar rats (200–250 g; n = 6–10 per group in both cases) underwent CION or sham surgery and were submitted repeatedly to application of heat (∼50 °C) to the ipsilateral or contralateral snout, delivered by a heat source placed 1 cm from the vibrissal pad. Decreases in latency to display head withdrawal or vigorous snout flicking were considered indicative of heat hyperalgesia. CION caused long-lasting heat hyperalgesia which started on Day 2 after surgery in both species and lasted up to Day 17 in mice and Day 10 in rats. Administration of DALBK or HOE-140 (peptidic B1 and B2 receptor antagonists, respectively; each at 3 nmol in 10 μl) onto the exposed infraorbital nerve of mice at the moment of surgery delayed the development of the thermal hyperalgesia. Systemic treatment on Day 5 (mice) or Day 4 (rats) with Des-Arg9, Leu8-Bradykinin (DALBK, B1 receptor antagonist, 0.1–1 μmol/kg, i.p.) or HOE-140 (B2 receptor antagonist, 0.001–1 μmol/kg, i.p.) transiently reduced heat hyperalgesia in both species. Due to the peptidic nature of DALBK and HOE-140, it is likely that their effects reported herein resulted from blockade of peripheral kinin receptors. Thus, mechanisms operated by kinin B1 and B2 receptors, contribute to orofacial heat hyperalgesia induced by CION in both mice and rats. Perhaps kinin B1 and B2 receptor antagonists might constitute effective preventive and curative treatments for orofacial thermal hyperalgesia induced by nerve injury.
Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic e... more Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30–1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, α-spinasterol and oleanolic acid (0.00001–10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300–1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30–600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-α and interleukin-1β. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, α-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
Mechanisms coupled to kinin B1 and B2 receptors have been implicated in sensory changes associate... more Mechanisms coupled to kinin B1 and B2 receptors have been implicated in sensory changes associated to various models of neuropathy. The current study aimed to investigate if kinins also participate in orofacial thermal hyperalgesia induced by constriction of the infraorbital nerve (CION), a model of trigeminal neuropathic pain which displays persistent hypersensitivity to orofacial sensory stimulation, in rats and mice. Male Swiss mice (30–35 g) or Wistar rats (200–250 g; n = 6–10 per group in both cases) underwent CION or sham surgery and were submitted repeatedly to application of heat (∼50 °C) to the ipsilateral or contralateral snout, delivered by a heat source placed 1 cm from the vibrissal pad. Decreases in latency to display head withdrawal or vigorous snout flicking were considered indicative of heat hyperalgesia. CION caused long-lasting heat hyperalgesia which started on Day 2 after surgery in both species and lasted up to Day 17 in mice and Day 10 in rats. Administration of DALBK or HOE-140 (peptidic B1 and B2 receptor antagonists, respectively; each at 3 nmol in 10 μl) onto the exposed infraorbital nerve of mice at the moment of surgery delayed the development of the thermal hyperalgesia. Systemic treatment on Day 5 (mice) or Day 4 (rats) with Des-Arg9, Leu8-Bradykinin (DALBK, B1 receptor antagonist, 0.1–1 μmol/kg, i.p.) or HOE-140 (B2 receptor antagonist, 0.001–1 μmol/kg, i.p.) transiently reduced heat hyperalgesia in both species. Due to the peptidic nature of DALBK and HOE-140, it is likely that their effects reported herein resulted from blockade of peripheral kinin receptors. Thus, mechanisms operated by kinin B1 and B2 receptors, contribute to orofacial heat hyperalgesia induced by CION in both mice and rats. Perhaps kinin B1 and B2 receptor antagonists might constitute effective preventive and curative treatments for orofacial thermal hyperalgesia induced by nerve injury.
Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic e... more Abstract: The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30–1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, α-spinasterol and oleanolic acid (0.00001–10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300–1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30–600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-α and interleukin-1β. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, α-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.
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Papers by Ana Paula Luiz