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Background and purpose: Pain and inflammation can be treated by various therapies that for the most part are not effective and can result in adverse effects. The current study was proposed to compare the antinociceptive and anti-inflammatory actions of curcumin and nano curcumin in rats. Experimental approach: Rats were randomly allocated into ten groups of six for formalin and tail-flick tests including the control group, curcumin and nano curcumin groups (20, 50, 100 mg/kg), morphine group (10 mg/kg), naloxone + 100 mg/kg curcumin group, and naloxone + 100 mg/kg nano curcumin group. There were nine groups for the carrageenan test. Groups 1-7 were the same as the previous division; groups 8 and 9 received 10 mg/kg diclofenac and 1% carrageenan, respectively. Findings/Results: All doses of nano curcumin significantly decreased the paw-licking time in both phases of the formalin test. In the tail-flick test, curcumin 100, nano curcumin 100, naloxone + curcumin 100, and naloxone + nano curcumin 100 showed significant analgesic effects compared to the control group. In the paw edema test, at 180 s after injection, curcumin (50 and 100 mg/kg) and all doses of nano curcumin significantly inhibited carrageenan-induced edema. Myeloperoxidase activity and lipid peroxidation decreased at doses of 50 and 100 mg/kg of curcumin but at three doses of nano curcumin (20, 50, and 100 mg/kg). Conclusion and implication: In conclusion, our results suggest that the nanoemulsion formulation of curcumin can be efficient in reducing pain and especially inflammation in lower doses compared to the native form of curcumin.

Spinal cord injury (SCI) starts with a mechanical and/or bio-chemical insult, followed by a secondary phase, leading progressively to severe collapse of the nerve tissue. Compared to the peripheral nervous system, injured spinal cord is characterized by weak axonal regeneration, which leaves most patients impaired or paralyzed throughout lifetime. Therefore, confining, alleviating, or reducing the expansion of secondary injuries and promoting functional connections between rostral and caudal regions of lesion are the main goals of SCI therapy. Interleukin 10 (IL-10), as a pivotal anti-inflammatory and immunomodulatory cytokine, exerts a wide spectrum of positive effects in the treatment of SCI. The mechanisms underlying therapeutic effects mainly include anti-oxidative stress, limiting excessive inflammation, anti-apoptosis, antinociceptive effects, etc. Furthermore, IL-10 displays synergistic effects when combined with cell transplantation or neurotrophic factor, enhancing treatment outcomes. This review lists pleiotropic mechanisms underlying IL-10-mediated neuroprotection after SCI, which may offer fresh perspectives for clinical translation. [ABSTRACT FROM AUTHOR]

Primary eosinophilic colitis (PEC) is a primary eosinophilic gastrointestinal disorder, and immunoglobulin/histamine complex (IHC) may be an effective therapeutic for PEC. IHC has a nonallergen‐specific antinociceptive effect in the treatment of histamine‐mediated pain. Key Clinical Message: An immunoglobulin/histamine complex effectively induced remission of primary eosinophilic colitis. It had both antinociceptive effects and nonallergen‐specific desensitization effects. [ABSTRACT FROM AUTHOR]

Prunus cerasus (P. cerasus) is an alternative-medicine used traditionally for amelioration of chronic-ailments marked by elevation in oxidative-stress like neuropathy. The oxidative-stress control was reported to ameliorate the inflammatory-process. This study aimed to phytochemically-investigate P. cerasus most-active phytochemicals utilizing in-vivo biological models to explore their gastroprotective, anti-inflammatory, and antinociceptive potentials and their possible mechanisms of action. Sonication with EtAc was used to extract P. cerasus fruit (Scf), and seed (Scs). The phytochemical-investigation of Scf was performed by RP-HPLC, while that of Scs was explored utilizing GC-FID. A bio-guided-fraction and isolation method was done utilizing column-chromatography, and have shown that cyanidin-3-glucoside (Cy3G) was the most-active constituent in Scf, while linoleic-acid (LA) was the most-active constituent in Scs. Scf, Scs, Cy3G, and LA significantly (p ˂ 0.05) protected the gastric-mucosa against HCl/EtOH-induced gastric-lesions. Scs (200 mg/kg) has shown the most gastroprotective-potentials, and had comparable-results to ranitidine (50 mg/kg). Scf, Scs, Cy3G, and LA have shown significant anti-inflammatory and antinociceptive potentials against carrageenan induced-edema and nociceptive-pain, respectively, where Scs (200 mg/kg) has shown the most anti-inflammatory and antinociceptive potentials, and had comparable results to ibuprofen (100 mg/kg). Scf, Scs, Cy3G, and LA have counter-acted carrageenan-induced oxidative-stress markers, with increased serum-catalase and reduced-glutathione levels, and decreased lipid-peroxidation. Histopathological-studies demonstrated gastroprotective potentials, regeneration and improvement of the spleen-structural architecture when treated with highest doses of Scs and Scf. The reduction of the pro-inflammatory TNF-alpha and IL-6, and elevation the anti-inflammatory factor IL-10 levels, spleen regenerative-capacity and oxidative-stress amelioration might be the main-mechanism responsible for P. cerasus anti-inflammatory potentials. P. cerasus appears to aid in ameliorating the inflammatory process, and reducing pain-thresholds while preserving the stomach.

Objective: Acanthus syriacus (AS) is one of the valuable herbal plants with immunomodulatory potentials. The aim of this study is to assemble a phytochemical investigation of A. syriacus exploring its anti-inflammatory and antinociceptive properties, identification of its most active compound(s) and elucidating their structure and determining their mechanisms of action. Materials and Methods: Bio-guided fractionation and isolation-schemes were used utilizing RP-HPLC, CC, 1H- and 13C-NMR, and biological-models were used to evaluate their effects against inflammation and neuropathic-pain (NP). Results: The outcomes showed that the most active fraction (FKCA) of AS was identified. Two of the three components of FKCA were identified by chromatographic-methods, while the third compound was isolated, its structure was elucidated and its was named Kromeic acid (KRA); FKCA contained Ferulic acid (27.5%), kromeic acid (48.1%), and chlorogenic acid (24.4%). AS, FKCA and KRA showed significant (p˂0.05) anti-inflammatory and antinociceptive potentials in the management of allodynia and thermal-hyperalgesia in NP. AS and FCKA showed comparatively equipotent antinociceptive-effects. FKCA showed higher antinociceptive effects than KRA suggesting additive-effects among FKCA components. The anti-inflammatory, insulin secretagogue, oxidative-stress reducing, and protective effects against NO-induced neuronal-toxicity might be amongst the possible mechanisms of tested compounds to alleviate NP. Conclusion: Here, we report the isolation and structure elucidation of a novel quinic-acid derivative, KRA. A. syriacus, FKCA, and KRA might be used as a novel complementary approach to ameliorate a variety of painful-syndromes.

Objective: Acanthus syriacus (AS) is one of the valuable herbal plants with immunomodulatory potentials. The aim of this study is to assemble a phytochemical investigation of A. syriacus exploring its anti-inflammatory and antinociceptive properties, identification of its most active compound(s) and elucidating their structure and determining their mechanisms of action. Materials and Methods: Bio-guided fractionation and isolationschemes were used utilizing RP-HPLC, CC, 1H- and 13C-NMR, and biological-models were used to evaluate their effects against inflammation and neuropathic-pain (NP). Results: The outcomes showed that the most active fraction (FKCA) of AS was identified. Two of the three components of FKCA were identified by chromatographic-methods, while the third compound was isolated, its structure was elucidated and its was named Kromeic acid (KRA); FKCA contained Ferulic acid (27.5%), kromeic acid (48.1%), and chlorogenic acid (24.4%). AS, FKCA and KRA showed significant (p<0.05) anti-inflammatory and antinociceptive potentials in the management of allodynia and thermal-hyperalgesia in NP. AS and FCKA showed comparatively equipotent antinociceptive-effects. FKCA showed higher antinociceptive effects than KRA suggesting additive-effects among FKCA components. The anti-inflammatory, insulin secretagogue, oxidative-stress reducing, and protective effects against NO-induced neuronal-toxicity might be amongst the possible mechanisms of tested compounds to alleviate NP. Conclusion: Here, we report the isolation and structure elucidation of a novel quinic-acid derivative, KRA. A. syriacus, FKCA, and KRA might be used as a novel complementary approach to ameliorate a variety of painful-syndromes. [ABSTRACT FROM AUTHOR]

BackgroundGabapentin is thought to exert an effect through the voltage-dependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test.MethodsSprague-Dawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining dose-response curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis.ResultsWhen a single drug was injected intrathecally, significant dose-dependent decreases in flinches were shown only in the late phase. ED50 values of intrathecal gabapentin and vitamin E in the late phase were 75.3 ± 9.58 µg, and 17.56 ± 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dose-dependent decreases in the number of flinches in both phases induced by the formalin test. The ED50 value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value.ConclusionsGabapentin and vitamin E (by itself) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test.

The antinociceptive effects of a lectin (LEC) isolated from the marine alga Amansia multifida were determined in Swiss mice. The LEC (1, 5, and 10 mg/kg) inhibited acetic acid-induced abdominal writhings in a dose-dependent manner after intraperitoneal or oral administration. A partial but significant inhibition of writhings was observed after the combination of LEC (10 mg/kg) with avidin (1 mg/kg), a potent inhibitor of the hemmaglutinant activity of the lectin. However, total writhing inhibition was demonstrable in the group of mice treated with LEC plus mannose (1 mg/kg), as compared to LEC alone or to control groups. Furthermore, avidin and mainly mannose also play a role in antinociception, somehow facilitating the interaction of LEC with its active cell sites. In the formalin test, although both phases of the response were significantly inhibited, the effect of LEC was predominant during phase 2, causing inhibition of licking time that ranged from 48 to 88% after oral (5 and 10 mg/kg) and intraperitoneal (1 to 5 mg/kg) administration. As is the case with morphine, the effect of LEC (2 mg/kg) was reversed by naloxone (2 mg/kg), indicating the involvement of the opioid system. LEC was also effective in the hot-plate test, producing inhibitory responses to the thermal stimulus, and its effects were blocked by naloxone. In the pentobarbital-induced sleeping time, although LEC did not alter the onset of sleep significantly, it increased the time of sleep within the same dose range compared to control. These results show that LEC presents antinociceptive effects of both central and peripheral origin, possibly involving the participation of the opioid system.

The present study was performed to explore the antinociceptive effects of the galanin receptor 1 agonist M617 in lateral habenula complex in rats. Intra-lateral habenula injection of 0.1, 0.5, 1 or 2 nmol of galanin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulations in rats. Furthermore, intra-lateral habenula injection of 0.1, 0.5, 1 or 2 nmol of the galanin receptor 1 agonist M617 also induced dose-dependent increases in HWLs to noxious thermal and mechanical stimulations in rats. Interestingly, there were no significant differences between the antinociceptive effects induced by intra-lateral habenula injection of 2 nmol of M617 and 2 nmol of galanin. The results indicate that galanin receptor 1 may be involved in the galanin-induced antinociceptive effects in the lateral habenula. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that antinociceptive effects of galanin and its receptors in nucleus accumbens (NAc) of rats with inflammatory pain provoked by subcutaneous injection of 0.1 ml of 2% carrageenin into the sole of the rat's left hindpaw. The hindpaw withdrawal latencies (HWLs) in response to thermal and mechanical stimulation significantly decreased in bilateral hindpaws at 3 and 4 hour after a subcutaneous injection of carrageenin. However intra-NAc injection of 2 and 3 nmol, but not 1 nmol of galanin markedly induced an increase in the HWLs in a dose-dependent way. Western blot also showed, that the expression of galanin receptor 1 (GalR1) and galanin receptor 2 (GalR2) were significantly upregulated in NAc at 3 hour after a subcutaneous injection of carrageenin. In addition, the rats were intra-NAc injected galanin, 5 min later following by intra-NAc injection of galanin receptor antagonist galantide, the galanin-induce antinociceptive effects were suppressed by galantide. The results demonstrated that galanin and its receptors might be involved in antinociception in the NAc of rats with inflammatory pain. [ABSTRACT FROM AUTHOR]

Administration of β-phenylethylamine (PEA), the simplest endogenous neuroamine, and various methylated PEA derivatives including α-methyl PEA (amphetamine, AMP) elicits analgesia in mice. Five or 20 min after intraperitoneal PEA injection of as little as 6 mg/kg resulted in an increased latency response time (from 2.4 ± 0.4 to 8.5 ± 2.3 or 7.0 ± 3.0 s, respectively) to the thermal stimulus (hot-plate test), which reached statistical significance at the 15 mg/kg (20 min; 13.1 ± 0.4 s) or 25 mg/kg dose (5 min; 15.3 ± 4.1 s). This PEA effect, was dose-dependent (albeit non-linear: 6, 12, 15, 25, 50 and 100 mg/kg), reached the cut-off time of 45 s at the upper PEA dose (5 min), and it was consistently enhanced by pretreatment with the monoamine oxidase inhibitor pargyline (P). Methylated PEA derivatives (15 and 100 mg/kg dose) produced various degrees of analgesia (in decreasing order p-Me PEA > PEA > N, N-diMe PEA > N-Me PEA) which, likewise to PEA itself, were consistently increased by P and declined over time (mice tested 5, 20 and 60 min after amine injection); small but statistically significant o- and β-Me PEA antinociceptive effects (5 min) were observed only at the higher dose (in the presence of P for β-Me PEA). A small analgesic effect was observed after the administration of AMP (5 or 10 mg/kg) which failed, even after P, to reach statistically significance. Independent of the amine and concentration tested, individual compound's antinociceptive properties were reliably increased by P (exception of AMP), decreased by reserpine (R) or haloperidol (H), and remained essentially unchanged after naloxone (N) administration suggesting the involvement of catecholamines, but not opioid peptides, in their observed analgesic effects. Injection of P + N produced results similar to those seen after P alone. Under the experimental conditions described neither P, R, H or N had any effects by themselves. These findings suggest additional understanding of the mechanism of action responsible for the analgesic effects of these amines would be of interest, leading further to controlled studies on their alleged usefulness as weight reducing agents and sport performance enhancers. [ABSTRACT FROM AUTHOR]

Abstract: The pharmacotherapy for the treatment of pain is an active area of investigation. There are effective drugs to treat this problem, but there is also a need to find alternative treatments free of undesirable side effects. In the present work the capacity of a series of flavonoids to bind to the μ opioid receptor was evaluated. The most active compound, 3,3-dibromoflavanone (31), a synthetic flavonoid, presented a significant inhibition of the binding of the selective μ opioid ligand [3H]DAMGO, with a Ki of 0.846 ± 0.263 μM. Flavanone 31 was further synthesized using a simple and cheap procedure with good yield. Its in vivo effects in mice, after acute treatments, were studied using antinociceptive and behavioral assays. It showed no sedative, anxiolytic, motor incoordination effects or inhibition of the gastrointestinal transit in mice at the doses tested. It evidenced antinociceptive activity on the acetic acid-induced nociception, hot plate and formalin tests (at 10 mg/kg and 30 mg/kg). The results showed that the 5-HT2 receptor and the adrenoceptors seem unlikely to be involved in its antinociceptive effects. Naltrexone, a nonselective opioid receptors antagonist, totally blocked compound 31 antinociceptive effects on the hot plate test, but naltrindole (δ opioid antagonist) and nor-binaltorphimine (κ opioid antagonist) did not. These findings demonstrated that 3,3-dibromoflavanone (31), at doses that did not interfere with the motor performance, exerted clear dose dependent antinociception when assessed in the chemical and thermal models of nociception in mice and it seems that its action is related to the activation of the μ opioid receptor. [Copyright &y& Elsevier]

Background: Gabapentin is thought to exert an effect through the voltage-dependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test. Methods: Sprague-Dawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining dose-response curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis. Results: When a single drug was injected intrathecally, significant dose-dependent decreases in flinches were shown only in the late phase. ED50 values of intrathecal gabapentin and vitamin E in the late phase were 75.3 ± 9.58 µg, and 17.56 ± 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dose-dependent decreases in the number of flinches in both phases induced by the formalin test. The ED50 value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value. Conclusions: Gabapentin and vitamin E (by itself ) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45 mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6-hydroxydopamine (6-OHDA), or depletion of descending serotonin by p-chlorophenylalanine (PCPA), abolished curcumin’s antinociceptive effect on mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic action of curcumin on mechanical stimuli was totally blocked by chronic co-treatment with the β2-adrenoceptor antagonist ICI 118,551, or by acute co-treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co-treatment with the 5-HT1A receptor antagonist WAY-100635 chronically, or with the irreversible mu-opioid receptor antangonist β-funaltrexamine acutely, completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli. Collectively, these findings indicate that the descending monoamine system (coupled with spinal β2-adrenoceptor and 5-HT1A receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’. [Copyright &y& Elsevier]

The present study examined the antinociceptive effects of ( O-methyl) N-benzoyl-tyramine (riparin I, ripI) isolated from the unripe fruit of Aniba riparia in chemical and thermal behavioral models of pain, such as acetic acid-induced abdominal writhing, formalin, and hot-plate tests in mice. Moreover, the involvement of the nitric oxide pathway as well as the opioid system in the antinociceptive action of ripI in the formalin test was investigated. RipI was administered both orally and intraperitoneally to male mice at single doses of 25 and 50 mg/kg. In the acetic acid-induced abdominal writhing, ripI decreased the number of writhings at both doses. In addition, in the formalin test, ripI reduced the paw licking time at both phases of the test. The effect of the highest dose of ripI in mice formalin test on the early phase was not reversed by naloxone (opioid receptor antagonist) but it was reversed by l-arginine (a nitric oxide precursor) in the late phase, suggesting that ripI may not act through opioid system and possibly acts through inhibition of nitric oxide pathway. In the hot-plate test, ripI increased the reaction time in the hot-plate test at the dose of 25 mg/kg, i.p., confirming the result found in the formalin test. Based on the obtained results, it is suggested that ripI presents antinociceptive activity that may be due to peripheral mechanisms (nitric oxide pathway) and central mechanisms, discarding the involvement of opioid system. [ABSTRACT FROM AUTHOR]

In the current study, we investigated the analgesic activity of a crude methanol extract and some fractions obtained from Hyeronima alchorneoides Allemao leaves and analyzed its phytochemical profile to determine active principles. All the fractions exhibited analgesic properties using the writhing test in mice, but the hexane fraction was the most active, causing 96.4 ± 1.0% inhibition at 10 mg/kg. Three compounds were isolated and identified based on their spectral data: simiarenol (1), β-sitosterol (2), and amentoflavone (3). Compound 1, a rare terpene isolated for the first time from the family Euphorbiaceae, presented a calculated ID 50 value of 18.87 (14.6–24.4)µmol/kg with the writhing test, being about 8-fold more active than two known analgesic and anti-inflammatory drugs (aspirin and dipyrone). In the formalin test, it was particularly active against the second phase, with inhibition of 59.5 ± 9%, suggesting a peripheral activity. In the capsaicin and glutamate tests, it showed inhibition of 52.3 ± 4 and 52.1 ± 6%, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Despite the diverse chemical structure of aspirin-like drugs, the antinociceptive effect of NSAIDs is mainly due to their common property of inhibiting cyclooxygenases involved in the formation of prostaglandins. Prostaglandins are potent hyperalgesic mediators which modulate multiple sites along the nociceptive pathway and enhance both transduction (peripheral sensitizing effect) and transmission (central sensitizing effect) of nociceptive information. Inhibition of the formation of prostaglandins at peripheral and central sites by NSAIDs thus leads to the normalisation of the increased pain threshold associated with inflammation. The contribution of peripheral and central mechanisms to the overall antinociceptive action of NSAIDs depends on several factors including the location of the targets of drug action, the site of drug delivery and the uptake and distribution to the site of action. The present work reviews the data on the regulation and location of cyclooxygenases at central and peripheral sites of the nociceptive pathway and focuses on the role of COX in the generation and maintenance of pain hypersensitivity. Experimental and clinical evidences are used to evaluate the significance of the peripheral and central antihyperalgesic effects of NSAIDs. [Copyright &y& Elsevier]

Abstract: Alpinia zerumbet (Pers.) Burtt. et Smith is an aromatic plant that is distributed widely in the tropical and sub-tropical regions of the world. In Brazil, where A. zerumbet is called “colonia”, it is used widely in folk medicine for the treatment of various diseases, including hypertension. In the present study, the antinociceptive effects of the orally administered essential oil of A. zerumbet (EOAz) were evaluated in male Swiss mice (20–25g each). In the acetic acid-induced writhing test, EOAz (30, 100 and 300mg/kgbodywt.; , and , respectively) was effective at all doses. In the hot-plate test, EOAz significantly increased the latency at doses of 100 and 300mg/kgbodywt., but not at 30mg/kgbodywt., at all observation times up to the 180th min ( for each dose). In the formalin test, EOAz significantly reduced paw licking time in the second phase of the test at 100mg/kgbodywt. (), but decreased it in both phases at 300mg/kgbodywt. (). At 30mg/kgbodywt., the effect of EOAz did not differ from control values in either phase of the formalin test (). Pretreatment with naloxone (5mg/kgbodywt., i.p.) caused a significant reversal of the analgesic effect of 300mg/kgbodywt. EOAz () that was complete for the first phase, but only partial for the second phase of the formalin test. The data show that orally administered OEAz promotes a dose-dependent antinociceptive effect, with a mechanism of action which probably involves the participation of opiate receptors. [Copyright &y& Elsevier]

The extract of Harpagophytum procumbens, widely utilized in Europe and, more recently, in other countries, is traditionally indicated to treat inflammatory processes. Harpagophytum procumbens acts by way of interleukins and leukocyte migration to the painful and inflamed joint area. Chemically, its secondary tuberous roots contains iridoid glycosides, harpagogide, procumbide, and harpagoside, as the active principle. The purpose of the present study was evaluate the therapeutic potential as anti-inflammatory and analgesic agent in rat model of Freund’s adjuvant-induced arthritis both in the acute and chronic phases. The animals were injected with Freund’s adjuvant in sub-plantar tissue of the right posterior paw and randomly assigned in acute (25, 50, or 100 mg/kg) or chronic (100 mg/kg) treatments with Harpagophytum procumbens solution test or vehicle. Then, submitted to behavioral test and assessment of body weight and right paw’s measurements. The results show that Harpagophytum procumbens extract increased the animals ‘latency of paws’ withdrawal, indicating a protective effect against the pain induced by the thermal stimulus, both in acute and chronic treatments. In addition to reduction in the right paw edema in the experimental groups when compared to control group. Thus, the data showed anti-inflammatory and peripheral analgesic properties of Harpagophytum procumbens extract with all doses tested, thus confirming its indication for inflammatory processes. [Copyright &y& Elsevier]

The calcium antagonist dihydropyridine derivative nimodipine and its enantiomers BAY N 5247, BAY N 5248, as well as BAY R 4407 (calcium antagonist (+)-enantiomer of the calcium agonist dihydropyridine BAY K 8644) do not exert antinociceptive effects in the rat as measured by the vocalization test in doses up to 100 μg/kg IV, and in the mouse as measured by the hot plate test in oral doses up to 100 mg/kg. The calcium agonists BAY K 8644 and BAY R 5417 ((−)-enantiomer of BAY K 8644) are also ineffective in the rat vocalization test but BAY K 8644 increases reaction time in the hot plate test (mouse) dose-dependently (1-10 mg/kg PO). μ-Receptor agonist (fentanyl) antinociceptive effects are potentiated by simultaneous IV administration of the calcium antagonists, the (−)-enantiomer of nimodipine BAY N 5248 being the most potent. This applies for the rat (vocalization test) and the mouse (hot plate test). The influence on fentanyl antinociception in the rat of the calcium agonist BAY K 8644 and its (−)-enantiomer BAY R 5417 is biphasic: low doses attenuate, high doses potentiate fentanyl antinociception. In the mouse (hot plate test) antinociceptive effects of BAY K 8644 plus fentanyl are less than additive, indicating that the calcium agonist decreases fentanyl effects. The relative potency of calcium antagonists in potentiation of fentanyl antinociception correlates with their relative potency as calcium antagonists as measured by receptor binding studies, effects on vascular and cardiac muscle, and with their neuropharmacological actions (anticonvulsive effects, inhibition of balance and spontaneous motility as well as tranquilizing effects in the mouse). It is concluded that calcium antagonism potentiates μ-receptor agonist antinociceptive effects, whereas calcium agonism antagonizes μ-receptor agonist antinociception. [ABSTRACT FROM AUTHOR]

Rats were treated with capsaicin (50 mg/kg, SC) either on the second day or on the second and third days of life. A significant attenuation of the responses to noxious stimuli was obtained in the capsaicin treated animals as measured by the hot-plate or paw pressure tests but not by the tail-flick test. Furthermore, neonatal capsaicin produced a significant reduction of response in the formalin test. Capsaicin reduced the reaction latency in rats with adjuvant arthritis as measured by the hot-plate and paw pressure tests, though capsaicin did not alter the overall time course of the response to Freund's adjuvant. Capsaicin also attenuated the weight loss or the decreased ambulatory and rearing behaviour which occurred in the control animals with adjuvant arthritis. It is suggested that neonatal treatment with capsaicin may relieve the responsiveness to longlasting nociceptive stimuli by adjuvant in rats. [ABSTRACT FROM AUTHOR]

The rostral ventromedial medulla (RVM) is highly involved in pain signal transmissions. Previous studies have shown that thalidomide is anti-nociceptive. Thus, we evaluated the neurobiological mechanisms of thalidomide in the RVM in the regulation of postoperative pain. We used a rat model of postoperative pain to investigate the effects of intra-RVM thalidomide treatments on postoperative pain, and evaluate the role of cannabinoid receptors in the effects of intra-RVM thalidomide treatments on GABAergic neurotransmission in the RVM neurons. We found intra-RVM thalidomide treatments reduced incisional surgery induced mechanical allodynia. This phenomenon was associated with attenuation of the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs (sIPSCs) in RVM neurons. Furthermore, applications of WIN 55,212-3 mesylate, a non-selective cannabinoid receptor antagonist reversed the effects of repeated thalidomide treatment on the frequency but not the amplitude of mIPSCs and sIPSCs. Finally, we found that repeated thalidomide treatment robustly enhanced CB2 receptor expression, but slightly reduced CB1 receptor expression, in the RVM. These results suggested that the antinociceptive effects of thalidomide in the RVM likely involve the attenuation of GABA release, which are critically regulated by cannabinoid receptors., (© 2017 Wiley Periodicals, Inc.)

The rhizomes of many Atractylodes species, including Atractylodes chinensis Koidzumi, Atractylodes macrocephala Koidzumi, and Atractylodes japonica Koidzumi, are collectively termed Atractylodis Rhizoma. We prepared n-hexane extracts of the three species and evaluated their anti-inflammatory effects on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among all n-hexane extracts, those of A. japonica most strongly inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 cells; five sesquiterpenes, atractylon, atractylenolide I, atractylenolide II, atractylenolide III, and 8-epiasterolid, were isolated from A. japonica. The phytochemical content of A. japonica was similar to those of A. chinensis and A. macrocephala. Moreover, the atractylon concentration was higher in A. japonica than in A. chinensis and A. macrocephala. Atractylon significantly inhibited NO and prostaglandin E2 production as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-induced RAW 264.7 cells. Atractylon (40 mg/kg) also significantly reduced the acetic-acid-induced writhing response, carrageenan-induced paw edema, and hot-plate latent pain response in mice. According to the results, A. japonica has anti-inflammatory and antinociceptive effects and atractylon is the major active component of A. japonica. Therefore, atractylon can be used as a bioactivity marker in A. japonica.