Involvement of CGRP and CGRP1 receptor in nociception in the nucleus accumbens of rats

The present study was performed to investigate the role of calcitonin gene-related peptide (CGRP) and its antagonist CGRP8-37 on nociception in the nucleus accumbens of rats. Hindpaw withdrawal latencies (HWLs) to noxious stimulation induced by hot plate and Randall Selitto tests were measured. The HWL to both thermal and mechanical stimulation increased significantly after intra-nucleus accumbens administration of 0.5 or 1 nmol of CGRP, but not 0.1 nmol, indicating that CGRP plays an anti-nociceptive effect in the nucleus accumbens of rats. The anti-nociceptive effect induced by intra-nucleus accumbens administration of 1 nmol of CGRP was blocked significantly by following intra-nucleus accumbens administration of 1 nmol of CGRP8-37, a selective antagonist of CGRP1 receptor. Furthermore, the HWLs to both thermal and mechanical stimulation decreased significantly after intra-nucleus accumbens administration of 0.02, 0.1 and 0.5 nmol of CGRP8-37 alone. The hyperalgesic effect of intra-nucleus accumbens administration of CGRP8-37 lasted for more than 60 min after the injection, suggesting that CGRP1 receptor is involved in anti-nociception in the nucleus accumbens of rats. The results indicate that CGRP and CGRP1 receptor have important roles in nociceptive modulation in the nucleus accumbens of rats.     

Antinociception Effect and Mechanisms of Campanula Punctata Extract in the Mouse

In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 µg) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α₂-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by α₂-adrenergic receptor, but not opioidergic and serotonergic receptors.     

The coastal medicinal plant Vitex rotundifolia: a mini-review on its bioactive compounds and pharmacological activity

Humans have long used natural remedies like plants and herbs to treat disease.Furthermore,research has been ongoing to find alternative pharmaceutical drugs based on traditionally used plants,as natural products show fewer side effects compared to synthetic drugs.Medicinal plants have long been targeted in drug development due to their bioactive compounds like alkaloids,flavonoids,and terpenoids.This is not only the case for terrestrial plants,but marine environments also provide a larger diversity of flora and fauna with medicinal bioactive compounds.Vitex rotundifolia,also known as Beach Vitex,is a coastal plant that has been traditionally used to treat a variety of diseases including premenstrual syndrome,headaches,migraines,colds,and eye pain.There have been many review papers on V.rotundifolia,emphasizing its taxonomy,distribution,and biological activity.Our current mini-review not only summarizes the pharmacology and bioactivity of V.rotundifolia,but it also provides new information on the main bioactive compounds of V.rotundifolia such as flavonoids,phenolic acid,and terpenes and their current pharmacological activity in vitro and in vivo research.This information can be useful for developing new pharmaceutical and nutraceutical agents to treat and manage disease.     

Involvement of oxytocin and its receptor in nociceptive modulation in the central nucleus of amygdala of rats

Studies have demonstrated that oxytocin plays important roles in pain modulation in the central nervous system. Oxytocin-ergic neurons are found in paraventricular nucleus and supraoptic nucleus of the hypothalamus. The oxytocin-ergic neurons send fibers from hypothalamus to amygdala and high density of oxytocin receptors are found in the central nucleus of amygdala (CeA). The present study was performed to investigate the influences of oxytocin and its receptors on nociceptive responses in the CeA of rats. Intra-CeA injection of 0.1, 0.5 or 1 nmol of oxytocin induced dose-dependent increases in the handpaw withdrawal latency induced by noxious thermal and mechanical stimulation in rats. The oxytocin-induced anti-nociception could be blocked by the selective oxytocin antagonist 1-deamino-2-d-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. The present study demonstrated that oxytocin and its receptors are involved in nociceptive modulation in the CeA of rats.     

Diclofenac increases the accumulation of kynurenate following tryptophan pretreatment in the rat: a possible factor contributing to its antihyperalgesic effect

Kynurenate, a metabolite of tryptophan formed serially from kynurenine, inhibits N-methyl-D-aspartate (NMDA) receptor responses. Non-steroidal anti-inflammatory drugs (NSAIDs) may produce anti-hyperalgesic effects by altering tryptophan metabolism to increase kynurenate concentrations. We examined whether the NSAID diclofenac (40 mg/kg, s.c.) or saline (control) increased kynurenine and kynurenate accumulation in tissues following pretreatment with tryptophan (200 mg/kg, i.p., 150 min before tissue harvesting). Significantly larger increases in kynurenine and kynurenate concentrations occurred when diclofenac followed tryptophan pretreatment (maximal, 60 min: plasma: by 58% and 49%; kidney: by 205% and 203%) when compared to control. Brain and spinal cord kynurenine concentrations increased maximally (120 min: by 39% and 95%) when diclofenac challenge followed tryptophan pretreatment. In brain, diclofenac increased kynurenate concentrations (20 min: by 274%). Diclofenac facilitated kynurenine and kynurenate accumulation in plasma and kidney, apparently by inhibiting renal elimination. This raises the possibility that (some) NSAIDs could act indirectly, with central and/or peripheral NMDA receptors contributing to their antihyperalgesic effects.     

Anti-nociceptive effect induced by intrathecal injection of ATPA,an effect enhanced and prolonged by concanavalin A

The present study investigated the effect of intrathecal injection of (RS)-2-alpha-amino-3-(3-hydroxy-5-tbutylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist to kainate receptor, on nociception in rats. Intrathecal administration of 1, 4 and 10 nmol of ATPA induced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats. Pretreatment with intrathecal injection of 300 microg of concanavalin A (ConA) to block the desensitization of kainate receptors enhanced and prolonged the anti-nociceptive effect induced by intrathecal injection of ATPA. The results suggest that the pre-synaptic kainate receptor in the primary afferent terminals is involved in the transmission of nociceptive information in dorsal horn of the spinal cord in rats. Furthermore, blocking the desensitization of kainate receptor enhanced and prolonged the ATPA-induced anti-nociceptive effects.     

Co-localization of substance P and Met-enkephalin-Arg-Gly-Leu in the intraspinal neurons of the rat, with special reference to the neurons in the substantia gelatinosa

A double-labeling immunofluorescence technique was employed to investigate the co-localization of the functionally antagonistic neuropeptides, substance P and enkephalins, within intraspinal neurons of the rat. Anti-Met-enkephalin-Arg⁶-Gly⁷-Leu⁸ (Enk-8) antiserum was used as a marker of the preproenkephalin A neuron system. The observations were focused on the lumbar spinal cord. Co-localization was most prominent within neurons in the substantia gelatinosa, in which more than 95% of substance P-like immunoreactivity neurons showed Enk-8-like immunoreactivity. These double-labeled cells corresponded to 45% of Enk-8-like immunoreactive neurons in the same area. This suggests that SP/Enk-8 interaction occurs at the axon terminals of the substantia gelatinosa neurons. In deeper layers of the dorsal horn (laminae III, IV), only 14% and 6% of SP-like immunoreactive and Enk-8-like immunoreactive neurons were double labeled, respectively. Co-localization was also observed in neurons located in the laminae I, V, VII and X, suggesting concomittant involvement of these peptides in a variety of spinal cord functions.     

Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 μg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α(2)-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by α(2)-adrenergic receptor, but not opioidergic and serotonergic receptors.     

Anti-Nociceptive and Anti-Inflammatory Effects of a Nigerian Polyherbal Tonic Tea (PHT) Extract in Rodents

The study investigated the anti-nociceptive and anti-inflammatory properties of a Nigerian Polyherbal Health Tonic tea aqueous extract (PHT) in rodents of both sexes. 100 – 500 mg kg⁻¹ of the aqueous extract was administered via the intra-peritoneal (i.p.) and oral (p.o.) routes to 5 groups of mice using tail immersion, tail clip, formalin and acetic acid-induced writhing tests of experimental nociceptive models. Each of the models showed that PHT possesses a significant (p<0.05) anti-nociceptive effects which were peripherally and centrally mediated as both the early and late phases of pain significantly (p<0.05) were inhibited. However, the peripherally mediated analgesic effect of PHT, although similar to that of aspirin but was found to be more potent than aspirin. In assessing its anti-inflammatory potentials, 300 – 1340 mg kg⁻¹ PHT was also administered via oral and intraperitoneal routes, which, significantly (p<0.05) reduced the volume of carrageenan-induced oedema. Although, PHT administered via i.p. route was more effective than the oral but there was barely any difference between the percentage inhibition of oedema volume at both 600 and 1340 mg kg⁻¹ given orally. PHT anti-inflammatory effect was elucidated to be significantly (p<0.05) mediated via histaminergic, serotonergic, bradykinin and prostaglandin inhibition. PHT was also shown to be more protective than acetylsalicylic acid (ASA) in the castor oil-induced diarrhea model, which suggests the involvement of other mechanisms. Thus, lending supports to its folkloric use in pain and swelling management.     

Anti-inflammatory,anti-nociceptive,and anti-psychiatric effects by the rhizomes of Alpinia officinarum on complete Freund's adjuvant-induced arthritis in rats

Ethnopharmacological relevance

Alpinia officinarum Hance (Zingiberaceae) is an annual plant. Its rhizome has long been used as an anti-inflammatory, an analgesic, a stomachic and a carminative in traditional medicine.

Objective

The aim of this study was to test the anti-inflammatory effects of Alpinia officinarum rhizomes on acute and chronic arthritis in SD rats.

Methods

Alpinia officinarum rhizomes were extracted by refluxing using 80% ethanol. The fractions were prepared by the fractionation of ethyl acetate (EtOAc), n-butanol, and water. This extract was administrated to rats by peroral injection. Acute arthritis was induced by a subcutaneous injection of carrageenan into the hind paw of SD rats. Chronic arthritis was stimulated by a subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw of SD rats. The paw volume was measured using a plethysmometer, thermal hyperalgesia was tested using a thermal plantar tester, hyperalgesia was evaluated by ankle flexion evoked vocalizations, and the expression of c-Fos in the brain hippocampus was measured with the avidin–biotin-peroxidase technique. Nitric oxide (NO) production was evaluated on nitrite by a Griess assay in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells.

Results

An 80% ethanolic extract showed acute anti-inflammatory activity that it reduced the edema volume in carrageenan-stimulated arthritis and inhibited NO generation in LPS-induced RAW 264.7 cells. In addition, this extract showed chronic anti-rheumatic and analgesic activities by suppressing the swelling volume, by recovering the paw withdrawal latency, and by inhibiting the flexion scores in CFA-induced arthritis. Particularly, this medicine had potent meaningful effects on the second signal of the left hind paw in the form of an immunological reaction compared to its effects on the first signal in the right hind paw after the CFA treatment. This also shows an anti-psychiatric effect through control of the expression of the c-Fos protein of the brain hippocampus in CFA-stimulated arthritis. On the other hand, each fraction showed acute anti-inflammatory effects; the action of the EtOAc fraction may have resulted from the suppression of NO production.

Conclusions

Alpinia officinarum rhizomes may be viable therapeutic or preventive candidates for the treatment of acute and chronic arthritis.