Antinociceptive effect of melatonin in the animal model of Parkinson’s Disease

2021 ◽  
Vol 4 (3) ◽  
pp. 440-452
Author(s):  
Tahsine Kosksi ◽  
Arem Selmi ◽  
Sahar Mani ◽  
Mriem Ben Rhouma ◽  
Sana Boughammoura ◽  
...  
Keyword(s):  
Animal Model ◽  
Mechanical Allodynia ◽  
Medial Forebrain Bundle ◽  
Antinociceptive Effect ◽  
Melatonin Treatment ◽  
Withdrawal Threshold ◽  
Melatonin Administration ◽  
Antinociceptive Effects ◽  
6 Hydroxydopamine ◽  
Antiallodynic Effect

Several animal experimental and clinical studies have shown the effectiveness of melatonin in the treatment of some symptoms of Parkinson's disease (PD). However, the antinociceptive effect of melatonin against pain associated to PD has not been fully investigated. Thus, the present study investigated the possible antiallodynic and antinociceptive effects of acute and chronic melatonin treatments in Parkinsonian model of rats. This model was created by unilateral injection of 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle (MFB). The electronic von Frey test was used to analyze the antiallodynic effect of melatonin on this PD animal model. In addition, c-Fos immunostaining was also used as a marker of nociception to evaluate the neuronal activity related to the nociception processing. The results showed that unilateral injection of 6-OHDA induced a significant decrease in paw withdrawal threshold in both ipsilateral and contralateral paws, which indicate mechanical allodynia induction. This allodynia was transitorily reversed by apomorphine as a dopamine agonist. Melatonin treatment significantly increased threshold of allodynia. Melatonin administration of both acutely or chronically significantly downregulated the c-Fos expression of neurons in 6-OHDA treated animals. In conclusion, 6-OHDA treatment can induces a bilateral mechanical hypernociception in rats while melatonin treatment produces profound antinociceptive effect. This finding paves the way to use melatonin as an antinociceptive agent for PD clinically.

scholarly journals L-Arginine-No System Participates in the Analgesic Effect of Flunixin Meglumine in the Rat

2016 ◽  
Vol 66 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Mirjana Milovanović ◽  
Sonja Vučković ◽  
Milica Prostran ◽  
Saša Trailović ◽  
Milan Jovanović
Keyword(s):  
Methyl Ester ◽  
Effective Dose ◽  
Analgesic Effect ◽  
Antinociceptive Effect ◽  
Painful Stimulus ◽  
Withdrawal Threshold ◽  
Flunixin Meglumine ◽  
Antinociceptive Effects ◽  
Pre Treatment

AbstractThis study investigated whether the L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 μg) into the rat’s hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a significant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was significantly increased in comparison with the effect of FM alone. L-arginine (L-ARG;10 mg/kg; i.p.) itself did not produce significant effect on carrageenan-induced hyperalgesia, but significantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.

scholarly journals Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 111
Author(s):  
Dayana da Costa Salomé ◽  
Natália de Morais Cordeiro ◽  
Tayná Sequeira Valério ◽  
Darlisson de Alexandria Santos ◽  
Péricles Barreto Alves ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Interleukin 1 ◽  
Antinociceptive Effect ◽  
Cholinergic Receptor ◽  
Hot Plate ◽  
Nitric Oxide Synthase Inhibitor ◽  
Antinociceptive Effects ◽  
Anti Inflammatory ◽  
Skin Affection ◽  
Synthase Inhibitor

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

scholarly journals The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Yan Dong ◽  
Chong-Yang Li ◽  
Xiao-Min Zhang ◽  
Ya-Nan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nucleus Accumbens ◽  
Pain Threshold ◽  
Antinociceptive Effect ◽  
Galanin Receptor ◽  
Pain Model ◽  
Withdrawal Threshold ◽  
Neuropathic Pain Model ◽  
Galanin Receptors ◽  
Intact Rats

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

scholarly journals Melatonin influences the early growth stage in Zoysia japonica Steud. by regulating plant oxidation and genes of hormones

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Di Dong ◽  
Mengdi Wang ◽  
Yinreuizhi Li ◽  
Zhuocheng Liu ◽  
Shuwen Li ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Transcriptome Analysis ◽  
Zoysia Japonica ◽  
Hormone Activity ◽  
Melatonin Treatment ◽  
Regulatory Pathways ◽  
Melatonin Administration ◽  
Seed Growth ◽  
Total Antioxidant ◽  
Plant Life Cycle

AbstractZoysia japonica is a commonly used turfgrass species around the world. Seed germination is a crucial stage in the plant life cycle and is particularly important for turf establishment and management. Experiments have confirmed that melatonin can be a potential regulator signal in seeds. To determine the effect of exogenous melatonin administration and explore the its potential in regulating seed growth, we studied the concentrations of several hormones and performed a transcriptome analysis of zoysia seeds after the application of melatonin. The total antioxidant capacity determination results showed that melatonin treatment could significantly improve the antioxidant capacity of zoysia seeds. The transcriptome analysis indicated that several of the regulatory pathways were involved in antioxidant activity and hormone activity. The hormones concentrations determination results showed that melatonin treatment contributed to decreased levels of cytokinin, abscisic acid and gibberellin in seeds, but had no significant effect on the secretion of auxin in early stages. Melatonin is able to affect the expression of IAA (indoleacetic acid) response genes. In addition, melatonin influences the other hormones by its synergy with other hormones. Transcriptome research in zoysia is helpful for understanding the regulation of melatonin and mechanisms underlying melatonin-mediated developmental processes in zoysia seeds.

scholarly journals Adeno-Associated Viral Delivery of GDNF Promotes Recovery of Dopaminergic Phenotype following a Unilateral 6-Hydroxydopamine Lesion

2002 ◽  
Vol 11 (3) ◽  
pp. 215-227 ◽  
Author(s):  
John Mcgrath ◽  
Elishia Lintz ◽  
Barry J. Hoffer ◽  
Greg A. Gerhardt ◽  
E. Matthew Quintero ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Viral Vectors ◽  
Medial Forebrain Bundle ◽  
Therapeutic Potential ◽  
Clinical Situation ◽  
Dopamine Neurons ◽  
Nigrostriatal System ◽  
Nigrostriatal Pathway ◽  
Neurotoxic Lesion ◽  
6 Hydroxydopamine

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopamine neurons that has been proposed for use in the treatment of Parkinson's disease (PD). Previous studies using viral vectors to deliver GDNF in rodent models of PD have entailed administering the virus either prior to or immediately after neurotoxin-induced lesions, when the nigrostriatal pathway is largely intact, a paradigm that does not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, recombinant adeno-associated virus carrying the gene encoding GDNF (rAAV-GDNF) was administered to animals bearing a maximal lesion in the nigrostriatal system, more closely resembling fully developed PD. Rats were treated with 6-hydroxydopamine into the medial forebrain bundle and assessed by apomorphine-induced rotational behavior for 5 weeks prior to virus administration. Within 4 weeks of a single intrastriatal injection of rAAV-GDNF, unilaterally lesioned animals exhibited significant behavioral recovery, which correlated with increased expression of dopaminergic markers in the substantia nigra, the medial forebrain bundle, and the striatum. Our findings demonstrate that rAAV-GDNF is capable of rescuing adult dopaminergic neurons from near complete phenotypic loss following a neurotoxic lesion, effectively restoring a functional dopaminergic pathway and diminishing motoric deficits. These data provide further support for the therapeutic potential of rAAV-GDNF-based gene therapy in the treatment of PD.

A radiotracer method for the measurement of central nervous system catecholamines in vivo

1978 ◽  
Vol 56 (3) ◽  
pp. 535-538 ◽  
Author(s):  
S. W. Tang ◽  
H. C. Stancer ◽  
J. J. Warsh
Keyword(s):  
Central Nervous System ◽  
Animal Model ◽  
Nervous System ◽  
Specific Activity ◽  
Brain Catecholamines ◽  
Radiotracer Method ◽  
New Strategy ◽  
The Central Nervous System ◽  
6 Hydroxydopamine

A new strategy for measurement of brain catecholamines was tested in an animal model. [3H]Norepinephrine was infused intravenously in rabbits to label the peripheral norepinephrine pools. The specific activity of urinary 3-methoxy-4-hydroxymandelic acid was consistently higher than that for 3-methoxy-4-hydroxyphenylglycol (MHPG). Central sympathectomy with 6-hydroxydopamine abolished this difference. Using the formula we propose, it is estimated that 30–50% of urinary MHPG originates from the central nervous system.

scholarly journals Clinical, behavioral and antinociceptive effects of crotalphine in horses

2015 ◽  
Vol 46 (4) ◽  
pp. 694-699
Author(s):  
Erica Cristina Bueno do Prado Guirro ◽  
João Henrique Perotta ◽  
Márcio de Paula ◽  
Yara Cury ◽  
Carlos Augusto Araújo Valadão
Keyword(s):  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Behavioral Changes ◽  
Behavioral Effects ◽  
Phase Iii ◽  
Intact Skin ◽  
Kappa Opioid ◽  
Antinociceptive Effects ◽  
Analgesic Peptide ◽  
Scapular Region

ABSTRACT: Crotalphine is a novel analgesic peptide that acts on kappa opioid and delta receptors, causing powerful analgesia in rats submitted to inflammatory, neuropathic or oncologic models of pain. This study evaluated clinical, behavioral and antinociceptive effects caused by crotalphine in horses, employing 18 Arabian horses and it was divided in three phases. In Phase I, "clinical and behavioral effects", crotalphine did not change the latency to urinate and defecate; did not modify the values of cardiac or respiratory rates, intestinal motility and rectal temperature; and did not cause significant ataxia, head, eye and lip ptosis. In Phase II, "antinociceptive effect on intact skin at scapular or ischial region", crotalphine did not cause significant analgesia. In Phase III, "antinociceptive effect on incised skin at scapular or ischial region", crotalphine promoted effective antinociceptive effects for six hours and inhibited hyperalgesia state for three days in the ischial region of horses submitted to incisional model of inflammatory pain, but crotalphine did not evoke relevant analgesic effect on the scapular region. Concluding, intravenous injection of a single dose of crotalphine (3.8ngkg-1) did not cause important clinical or behavioral changes and promotes antinociceptive effect on incised ischial region for seven days in horses. Moreover, crotalphine did not evoke relevant anti nociceptive effect on the scapular region or in intact skin of horses.

scholarly journals 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

2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
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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