Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

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Pre-treatment Effect of Kombucha Tea on Analgesia and Inflammation in Male Rat

Zahedan Journal of Research in Medical Sciences ◽

10.5812/zjrms.85049 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Zahra Rabiei ◽

Zahra Lorigooini ◽

Fatemeh Firuzi ◽

Mohammad Rahimi-Madiseh

Keyword(s):

Acetic Acid ◽

Pain Tolerance ◽

Male Rat ◽

Control Group ◽

Tail Flick ◽

Tail Flick Test ◽

Analgesic Effects ◽

Kombucha Tea ◽

Anti Inflammatory

Background: The use of natural compounds in relieving pain has been commonplace since ancient times and their use is currently increasing. Objectives: Given that analgesic and anti-inflammatory effects of Kombucha have not been studied, this study was designed to examine these effects in vitro. Methods: In this experimental study, rats were divided into four groups. The control group received normal saline i.p in the same amount of the drug. The other groups received Kombucha tea i.p at 250, 500, and 1000 mg/kg. Tail-flick and acetic acid tests were used to evaluate the analgesic effects of Kombucha tea and the xylene-induced ear inflammation test to evaluate the anti-inflammatory effects of Kombucha tea. Results: Kombucha tea at three doses 250, 500, and 1000 mg/kg significantly reduced the number of writhings in the acetic acid test. Kombucha tea at 1000 mg/kg significantly increased pain tolerance in the tail-flick test. Kombucha tea at 250 and 500 mg/kg could significantly reduce inflammation in the rat’s ear. Conclusions: The results of this study indicate that Kombucha has analgesic effects in rats and can be considered in future treatments.

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Analgesic activity of allopurinol and febuxostat in experimental animals

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20181005 ◽

2018 ◽

Vol 7 (4) ◽

pp. 603

Author(s):

Yajnesh P. Sahu ◽

Sachchidanand Pandey ◽

Sabita Mohapatra

Keyword(s):

Acetic Acid ◽

Analgesic Activity ◽

Physical Dependence ◽

Experimental Pain ◽

Opioid Analgesics ◽

Analgesic Nephropathy ◽

Tail Flick ◽

Tail Flick Test ◽

Analgesic Effects ◽

Peripheral Analgesia

Background: Currently, two classes of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are used to manage pain in different clinical situations. Chronic uses of these drugs have various adverse effects like gastric ulceration/bleeding, analgesic nephropathy and respiratory depression, physical dependence, addiction, respectively. Xanthine oxidase inhibitors, used for chronic gout, might have a role in alleviation of pain, as per literature survey. Hence, the present study was carried out to evaluate the potential analgesic activity of allopurinol and febuxostat in different experimental models.Methods: The analgesic activity of allopurinol and febuxostat was assessed by employing two different experimental pain models-tail flick latency model in rats for central analgesia and acetic acid induced writhing model in mice for peripheral analgesia and was compared with tramadol and aspirin.Results: Allopurinol and febuxostat produced significant central and peripheral analgesic effects as is evident from increase in reaction time in tail flick test and inhibition in number of writhes in acetic acid induced writhing test.Conclusions: The results of the present study demonstrate marked analgesic effect of allopurinol and febuxostat.

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Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root ofSchoenoplectus grossus

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/3820704 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Nirmal Kumar Subedi ◽

S. M. Abdur Rahman ◽

Mohammad Ahsanul Akbar

Keyword(s):

Acetic Acid ◽

Petroleum Ether ◽

Methanol Extract ◽

Diclofenac Sodium ◽

Radiant Heat ◽

Tail Flick ◽

Dependent Manner ◽

Tail Flick Test ◽

Standard Drug ◽

Pain Models

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root ofSchoenoplectus grossususing acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P<0.001andP<0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P<0.001) after second hour. These findings suggest that the root extracts ofS. grossuspossess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

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Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.83577 ◽

2011 ◽

Vol 02 (02) ◽

pp. 130-136 ◽

Cited By ~ 9

Author(s):

Keshab Raj Paudel ◽

SK Bhattacharya ◽

GP Rauniar ◽

BP Das

Keyword(s):

Pain Perception ◽

Late Phase ◽

Antinociceptive Effect ◽

Experimental Pain ◽

Mechanical Hyperalgesia ◽

Tail Flick ◽

Hot Plate ◽

Analgesic Effects ◽

Pain Models ◽

Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

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Preliminary assessment of the anti-inflammatory and analgesic effects of methanol leaf extract of Cussonia barteri (Araliaceae) in rodents

Herba Polonica ◽

10.2478/hepo-2019-0015 ◽

2019 ◽

Vol 65 (3) ◽

pp. 22-31

Author(s):

Ighodaro Igbe ◽

Osaze Edosuyi ◽

Agbonlahor Okhuarobo ◽

Adarki Pongri ◽

Nkechi Maduako ◽

...

Keyword(s):

Acetic Acid ◽

Analgesic Effect ◽

Leaf Extract ◽

Methanol Extract ◽

Tail Flick ◽

Hot Plate ◽

Analgesic Effects ◽

Paw Oedema ◽

Anti Inflammatory ◽

Ear Oedema

Summary Introduction: Potato (Solanum tuberosum L.) is an important vegetable crop in Syria. Potato tuber moth Cussonia barteri is a small tree that grows in the sub-Saharan part of Africa. Various parts of the plant are used for the treatment of a variety of ailments in ethno-medicine. Objective: To evaluate the anti-inflammatory and analgesic effect of the methanol leaf extract of Cussonia barteri. Material and methods: The leaves were air-dried, powdered and repeatedly extracted with methanol using a Soxhlet apparatus. The resulting methanol extract (100, 200 and 400 mg/kg) was evaluated for anti-inflammatory activity using carrageenan-induced paw oedema, xylene-induced ear oedema and formalin-induced arthritis tests. Analgesic effect was evaluated using acetic acid-induced mouse writhing, hot plate and tail flick tests. Results: All doses of the extract significantly (p<0.05) reduced carrageenan-induced paw oedema, however the 400 mg/kg dose gave a sustained effect. The extract significantly inhibited xylene induced ear oedema at all doses. There were no significant (p>0.05) reductions in paw swellings due to formalin. In the acetic acid induced writhing test, the extract significantly (p<0.05) decreased writhing at 400 mg/kg only. Reaction times were not significantly different from the control in the hot plate and tail flick tests. Conclusion: This study has shown that the methanol extract possesses acute anti-inflammatory and peripherally mediated analgesic effects.

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Antinociceptive Profiles of Platycodin D in the Mouse

The American Journal of Chinese Medicine ◽

10.1142/s0192415x04001916 ◽

2004 ◽

Vol 32 (02) ◽

pp. 257-268 ◽

Cited By ~ 18

Author(s):

Seong-Soo Choi ◽

Eun-Jung Han ◽

Tae-Hee Lee ◽

Ki-Jung Han ◽

Han-Kyu Lee ◽

...

Keyword(s):

Antinociceptive Effect ◽

Control Level ◽

Tail Flick ◽

Triterpene Saponins ◽

Tail Flick Test ◽

Platycodin D ◽

Pain Models ◽

Antinociceptive Effects ◽

Dose Dependent ◽

Higher Doses

Platycodin D (PD), one of several triterpene saponins, was isolated from roots of Platycodon grandiflorum. We previously reported that intracerebroventricular (i.c.v.) administration of PD showed an antinociceptive effect as measured by the tail-flick assay. However, its exact role in the regulation of antinociception in the various types of pain models has not yet been characterized. Thus, we attempted to find antinociceptive profiles of PD in various pain models. PD administered intraperitoneally (i.p.), i.c.v. or intrathecally (i.t.) showed antinociceptive effects in dose-dependent manners as measured by the tail-flick, writhing and formalin tests. In the tail-flick test, PD at the low doses reached the peak after 15 minutes and returned to the control level after 60 minutes. However, higher doses of PD showed a strong antinociception at least for 1 hour. PD administered i.t. showed stronger antinociception than that induced by i.c.v. administration PD in both tail-flick and writhing tests. In the formalin test, PD administered i.p., i.c.v. or i.t. showed antinociceptive effects during both the first (direct nociceptive stimulation) and second (late inflammatory) phases. Pretreatment with naltrexone i.p., i.c.v. or i.t. did not affect PD-induced inhibition of the tail-flick response. Our results suggest that PD shows a strong antinociceptive effect on the tail-flick, writhing and formalin tests, acting on central nervous system. However, PD-induced antinociception may not be mediated by the opioid receptors.

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Acute toxicity, anti-inflammatory, analgesic and antipyretic effects of aqueous and hydroethanolic extracts of Brenania brieyi (Rubiaceae)

Open Access Research Journal of Biology and Pharmacy ◽

10.53022/oarjbp.2021.3.1.0050 ◽

2021 ◽

Vol 3 (1) ◽

pp. 019-032

Author(s):

Nkundineza JC ◽

Nsonde Ntandou GF ◽

Boumba LS ◽

Kibamgou S ◽

Motondo E ◽

...

Keyword(s):

Acetic Acid ◽

Acute Toxicity ◽

Aqueous Extract ◽

Ethanolic Extract ◽

Tail Flick ◽

Pharmacological Effects ◽

Tail Flick Test ◽

Ethanolic Extracts ◽

Anti Inflammatory ◽

Inflammatory Effect

Brenania brieyi (Rubiaceae) is widely used in traditional Congolese medicine in the treatment of many pathologies that are manifested by inflammation, pain and fever. The objective of this study was to study the acute toxicity as well as to evaluate the antipyretic, analgesic and anti-inflammatory effects of the aqueous and hydro-ethanolic extracts of Brenania brieyibark on models of pyrexia, algesia and inflammation induced in rodents. The aqueous extract of Brenania brieyidoes not cause any mortality up to the dose of 4000 mg/kg, but promotes a slight increase in body weight. From 2000 mg/kg, the signs of toxicity observed were the significant decrease in mobility as well as the loss of alertness. At doses of 100 and 200 mg/kg, aqueous and hydro-ethanolic Brenania brieyiextracts showed a very significant anti-inflammatory effect (***p< 0.001) on edemas induced by carrageenin (1%), formaldehyde (2.5%) and histamine (1 mg/mL), greater than that of diclofenac at 10 mg/kg. At 200 mg/kg, both extracts showed a very significant analgesic effect (***p< 0.001), greater than that of paracetamol 100 mg/kg against pain induced by acetic acid 0.6% and formaldehyde 2.5%. Brenania brieyiwas slightly effective in the tail flick test. Brewer's yeast-induced hyperthermia was reduced by both extracts. However, the hydro-ethanolic extract proves to be more effective than the aqueous extract in all the tests carried out. These pharmacological effects would be related to the presence of alkaloids, tannins, flavonoids, anthraquinones, oses and saponosides.

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Comparison of analgesic activities of aconitine in different mice pain models

PLoS ONE ◽

10.1371/journal.pone.0249276 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249276

Author(s):

Jianhua Deng ◽

Jiada Han ◽

Jiahao Chen ◽

Yanmin Zhang ◽

Qiuju Huang ◽

...

Keyword(s):

Acetic Acid ◽

Visceral Pain ◽

Thermal Stimulus ◽

Diterpenoid Alkaloids ◽

Hot Plate ◽

Pain Model ◽

Analgesic Effects ◽

Pain Models ◽

Nociceptive Responses ◽

Analgesic Activities

Aconitine (AC) is the primary bioactive and secondary metabolite alkaloidin of Aconitum species which is accounted for more than 60% of the total diester-diterpenoid alkaloids in Aconite. To evaluate the analgesic effects of AC, 4 different pain models including hot plate assay, acetic acid writhing assay, formalin and CFA induced pain models were adopted in this study. In hot plate experiment, AC treatment at concentration of 0.3 mg/kg and 0.9 mg/kg improved the pain thresholds of mice similar to the positive drug aspirin at the concentration of 200 mg/kg (17.12% and 20.27% VS 19.21%). In acetic acid writhing experiment, AC significantly reduced the number of mice writhing events caused by acetic acid, and the inhibition rates were 68% and 76%. These results demonstrated that AC treatment revealed significant analgesic effects in both acute thermal stimulus pain model and chemically-induced visceral pain model. The biphasic nociceptive responses induced by formalin were significantly inhibited after AC treatment for 1h or 2h. The inhibition rates were 33.23% and 20.25% of AC treatment for 1h at 0.3 mg/kg and 0.9 mg/kg in phase I. In phase II, the inhibition rates of AC and aspirin were 36.08%, 32.48% and 48.82% respectively, which means AC showed similar analgesic effect to non-steroidal anti-inflammatory compounds. In the chronic CFA-induced nociception model, AC treatment also improved mice pain threshold to 131.33% at 0.3 mg/kg, which was similar to aspirin group (152.03%). Above all, our results verified that AC had obviously analgesic effects in different mice pain models.

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Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain

10.1101/2020.10.16.341776 ◽

2020 ◽

Author(s):

Fani Pantouli ◽

Travis W. Grim ◽

Cullen L. Schmid ◽

Agnes Acevedo-Canabal ◽

Nicole M. Kennedy ◽

...

Keyword(s):

Repeated Administration ◽

Spinal Reflex ◽

Tail Flick ◽

Tail Flick Test ◽

Pain Model ◽

Thermal Nociception ◽

Cellular Assays ◽

Pain Models ◽

Gtpγs Binding ◽

Repeated Dosing

AbstractThe mu opioid receptor-selective agonist, SR-17018, preferentially activates GTPγS binding over βarrestin2 recruitment in cellular assays. In mice, SR-17018 stimulates GTPγS binding in brainstem and produces antinociception with potencies similar to morphine. However, it produces much less respiratory suppression and mice do not develop antinociceptive tolerance in the hot plate assay upon repeated dosing. Herein we evaluate the effects of acute and repeated dosing of SR-17018, oxycodone and morphine in additional models of pain-related behaviors. In the mouse warm water tail immersion assay, an assessment of spinal reflex to thermal nociception, repeated administration of SR-17018 produces tolerance as does morphine and oxycodone. SR-17018 retains efficacy in a formalin-induced inflammatory pain model upon repeated dosing, while oxycodone does not. In a chemotherapeutic-induced neuropathy pain model SR-17018 is more potent and efficacious than morphine or oxycodone, moreover, this efficacy is retained upon repeated dosing of SR-17018. These findings demonstrate that, with the exception of the tail flick test, SR-17018 retains efficacy upon chronic treatment across several pain models.

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