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Caesalpinia eriostachys Benth. (CE) is native to the Mexico and multiple effects have been observed from several plants belonging to the same family. CE was subjected to extraction with 95% ethanol, and the components were isolated through column chromatography. The structure of the compound was elucidated based on nuclear magnetic resonance (NMR) spectral data, electron ionization–mass (EI‐MS) spectroscopy, and liquid chromatography–mass (LC‐MS) spectroscopy. In vivo antinociceptive studies were conducted using writhing, 5% formalin, tail‐flick, hot‐plate, and von Frey filament tests. The ethanolic extract showed a significant effect in the acetic acid‐induced pain model and nociceptive behavior in the formalin model (second phase). In hot‐plate test and tail‐flick test, the results showed no difference compared to the control group. The results suggest that the ethanolic extract may act peripherally to reduce pain. In the streptozotocin (STZ)‐induced pain model, the ethanolic extract showed significant effect in the von Frey test model. The n‐Hex (Hexane) and MC (Methylene chloride) fractions and isolated compounds, ellagic acid and agathisflavone, showed increased effect. Based on these results, we confirmed that the CE ethanolic extract and their compounds, ellagic acid and agathisflavone, have antinociceptive effect on diabetes mellitus‐induced pain. Furthermore, the results of this study might be valuable for identifying compounds with antinociceptive activity from natural products. [ABSTRACT FROM AUTHOR]

Background: There is a wide range of animal models available today for studying chronic pain associated with a variety of etiologies and an extensive list of clinical manifestations of peripheral neuropathies. Photobiomodulation is a new tool for the treatment of pain in a convenient, noninvasive way. Objective: The aim of this work is to elucidate the effects of infrared light‐emitting diodes (LEDs) on behavioral responses to nociceptive stimuli in chronic pain models. Methods: Forty‐eight Swiss male mice weighing 25 to 35 g were used. Two chronic pain models, ischemia‐reperfusion (IR) and spared spinal nerve injury, were performed and then treated with infrared LED irradiation (390 mW, 890 nm, 17.3 mW/cm2, 20.8 J/cm2, for 20 minutes). The behavioral tests used were a mechanical hypersensitivity test von Frey test) and a cold allodynia test (acetone test). Results: The results showed that, in the IR model, the infrared LED had a significant effect on mechanical stimulation and cold allodynia on every day of treatment. In the spared nerve injury model, an analgesic effect was observed on every treatment day (when started on the 3rd and 7th days after the surgery). In both models, the effect was abolished when the treatment was interrupted. Conclusions: These findings suggest that photobiomodulation therapy may be a useful adjunct treatment for chronic pain. [ABSTRACT FROM AUTHOR]

The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro- l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole also blocked CaCl2-induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1 H-pyrazol-4-yl]-2 H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K+ channels observed in the vasorelaxant effect. [ABSTRACT FROM AUTHOR]

It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/ OFQ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/ OFQ receptor ( NOP) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/ OFQ levels in pain-related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague-Dawley rats. N/ OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212-2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC-801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212-2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/ OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212-2 was combined with JTC-801. We hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/ OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2. Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions. [ABSTRACT FROM AUTHOR]

A novel µ-opioid receptor (MOR) subtype, named MOR-1B, derived from alternatively spliced variants of MOR gene, has been isolated from the rat brain. Here we found for the first time that CXBK recombinant-inbred mice display a significant reduction in the expression of MOR-1B mRNA in the brain as compared to that in their progenitor C57BL/6 mice. In contrast, the expression level of MOR-1 mRNA in the brain of CXBK mice was similar to that found in C57BL/6 mice. Furthermore, relatively lower levels of MOR-1B immunoreactivity were detected in the periaqueductal grey matter (PAG) of CXBK mice than that observed in C57BL/6 mice. To investigate further the possible changes in MOR function to activate G-proteins under the condition of a reduced MOR-1B expression, the guanosine-5′- o-(3-[35S]thio)triphosphate ([35S]GTPγS) binding assay was performed. We found that the increased level of [35S]GTPγS bindings to whole brain membranes induced by a selective MOR agonist endomorphin-1 was significantly decreased in CXBK mice, indicating that CXBK strain can be classified as MOR-1B-knockdown mice. We next investigated whether intracerebroventricular (i.c.v.) pretreatment with an antisence oligodeoxynucleotide against exon 5 of MOR gene (MOR-1B) could affect the endomorphin-1-induced supraspinal antinociception. The i.c.v. pretreatment with antisence oligodeoxynucleotide against MOR-1B produced a significant reduction in the i.c.v.-administered endomorphin-1-induced antinociceptive effect. The present data provide first evidence that a lack of MOR-1B expression may, at least in part, contribute to the reduced sensitivity to MOR agonists in CXBK mice, and MOR-1B may play a potential role in the MOR-mediated supraspinal antinociception. [ABSTRACT FROM AUTHOR]

Background: Thiopental has hypnotic actions in the brain, but it also depresses nociceptive transmission. In this study we examined whether thiopental had direct (spinal) and/or indirect (supraspinal) effects on the responses of single lumbar dorsal horn neurons to noxious mechanical stimulation, using a method to deliver thiopental differentially to either the torso or cranial circulation in goats.Methods: Goats (n=10) were anesthetized with isoflurane and neck dissections performed to permit cranial bypass. A lumbar laminectomy was made to permit single-unit recording of lumbar dorsal horn neuronal activity (1-2 neurons/animal). Isoflurane was maintained at 0.8+/-0.1% to both head and torso throughout the study. During cranial bypass, thiopental was separately administered to the torso (low dose, 1.5+/-0.5 mg/kg; high dose, 3.7+/-0.5 mg/kg) or cranial (low dose, 0.12+/-0.03 mg/kg; high dose, 0.2 mg/kg) circulation.Results: Thiopental administered to the torso significantly depressed dorsal horn neuronal responses to noxious stimulation at the high dose: 757+/-471 to 392+/-305 impulses/min at 1 min post-injection, P<0.006 (n=14); evoked responses recovered at 5 min post-injection. At the low dose, there was a similar numerical decrease, but this did not reach significance: 876+/-780 to 407+/-499 impulses/min at 1 min post-injection, P>0.05 (n=6). No significant change was observed when thiopental was administered to the cranial circulation: low dose, 1061+/-1167 to 965+/-874 impulses/min at 1 min post-injection, P>0.05 (n=10); high dose, 864+/-331 to 917+/-525 impulses/min at 1 min post-injection, P>0.05 (n=8).Conclusion: Thiopental has a direct (spinal) depressant effect on dorsal neuronal responses to noxious stimulus, but no significant supraspinal effect. [ABSTRACT FROM AUTHOR]

The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl 2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K + channels observed in the vasorelaxant effect., (© 2016 John Wiley & Sons A/S.)