Analgesic effects of cannabinoid receptor agonist WIN55,212-2 in the nucleus cuneiformis in animal models of acute and inflammatory pain in rats

2011 ◽  
Vol 1420 ◽  
pp. 19-28 ◽  
Author(s):  
Mohammad Ebrahimzadeh ◽  
Abbas Haghparast
Keyword(s):  
Animal Models ◽  
Inflammatory Pain ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Analgesic Effects

scholarly journals Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianle Gao ◽  
Tao Li ◽  
Wei Jiang ◽  
Weiming Fan ◽  
Xiao-Jun Xu ◽  
...  
Keyword(s):  
Animal Models ◽  
Inflammatory Pain ◽  
Extracellular Fluid ◽  
Postoperative Pain Management ◽  
Assay Method ◽  
Pharmacokinetic Studies ◽  
Analgesic Effects ◽  
Pain Models ◽  
Potential Benefits ◽  
Incisional Pain

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.

Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study

Life Sciences ◽  
2019 ◽  
Vol 232 ◽  
pp. 116670 ◽  
Author(s):  
Elahe Mohammadi Vosough ◽  
Vafa Baradaran Rahimi ◽  
Seyyed Ali Masoud ◽  
Hamid Reza Mirkarimi ◽  
Maryam Kazemi Demneh ◽  
...  
Keyword(s):  
Animal Models ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Mechanistic Study ◽  
Protective Effects

Cannabinoids as Analgesics for Pain in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 822-822
Author(s):  
Divyanshoo Rai Kohli ◽  
Yunfang Li ◽  
Sergey G Khasabov ◽  
Marna E Ericson ◽  
Pankaj Gupta ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Receptor Agonist ◽  
Pain Sensitivity ◽  
Grip Force ◽  
Cannabinoid Receptor ◽  
Nerve Fibers ◽  
Deep Tissue ◽  
Withdrawal Threshold ◽  
Heat Stimulus ◽  
Cp 55,940

Abstract Abstract 822 Neural mechanisms underlying severe pain in sickle cell disease (SCD) remain unknown. Opioids, the primary medications for pain in SCD, are frequently associated with development of tolerance and side effects. We used transgenic heterozygous BERK mice expressing human sickle hemoglobin (hBERK) and age/sex matched mice of similar genetic background expressing normal human hemoglobin (HbA-BERK) to examine changes in skin morphology and innervation that may relate to behavioral measures of pain. Since cannabinoids have shown promise in treating inflammatory and neuropathic pain, we examined the ability of cannabinoids to treat pain in hBERK (sickle) and control mice. The epidermis and dermis were thinner in hBERK mice (p< 0.01). Confocal microscopy showed that pan-neuronal marker protein gene product 9.5 (PGP) immunoreactive nerve fibers in the epidermis and dermis were disorganized and that the dermis had fewer nerve fibers in hBERK than HbA-BERK mice. Expression of Calcitonin Gene Related Peptide and Substance P, neuropeptides found in nociceptive afferent fibers, was increased in hBERK skin, suggesting neuronal sensitization. We next examined pain sensitivity in hBERK and HbA-BERK mice. Paw Withdrawal Frequency (PWF) per 10 applications of a 1.0 g von Frey monofilament and 50% paw withdrawal threshold evoked by von Frey monofilaments ranging from 0.4 to 8.0 g were used to assess mechanical sensitivity. hBERK mice showed 277.6 ± 83% higher PWF and 35.9 ± 26% lower paw withdrawal threshold than HbA-BERK (p<0.05). PWF increased consistently with age in hBERK (p<0.01; 5 vs. 15 mo) but not in HbA-BERK mice, suggesting increasing mechanical hyperalgesia with age in sickle mice. We observed a 24.4 ± 2% decrease in paw withdrawal latency (PWL) in response to a radiant heat stimulus applied to the plantar surface of the hind paw in hBERK vs. HbA-BERK (p<0.01). Both HbA-BERK and hBERK females exhibited lower PWL than their male counterparts (p<0.01 & p<0.05 in hBERK & HbA-BERK, respectively). Thus, mice with SCD show increased sensitivity to a noxious heat stimulus. When placed on a cold plate at 4°C for 2 min, hBERK mice exhibited a 72 ± 17% increase in PWF and 45.1 ± 11% decrease in PWL compared to HbA-BERK mice (p<0.01 for PWF and PWL). Finally, we examined deep tissue/musculoskeletal hyperalgesia by measuring maximum forepaw grip force. hBERK mice had 26.9 ± 10% lower grip force response compared to age/sex matched HbA-BERK mice (p<0.01). Hence, hBERK mice exhibited increased deep tissue hyperalgesia and sensitivity to mechanical and thermal stimuli. We evaluated the ability of the cannabinoid receptor agonist CP 55,940, to decrease deep tissue hyperalgesia. Intra-peritoneal injection of 0.3 mg/kg CP 55,940 improved grip force responses in hBERK mice in a time dependent manner (p<0.01; baseline vs. 0.5, 1, 1.5 and 3 h post-injection), while no change was seen in age/sex matched HbA-BERK mice, or mice injected with vehicle. Anti-nociception following CP 55,940 was not due to catalepsy. Increase in grip force response following CP 55,940 injection demonstrates that hBERK mice have tonic hyperalgesia that is sensitive to cannabinoids. To simulate the inflammatory pain of SCD, we induced inflammatory pain using Freund's Complete Adjuvant (CFA) and then evaluated the analgesic effect of the cannabinoid receptor agonist CP 55,940 using the von Frey test. Intra-plantar injection of 10 mg CFA resulted in increased PWF in the inflamed paw (p<0.01; baseline vs. 24 h post-injection in hBERK and HbA-BERK mice). Subsequent intra-plantar injection of 10 mg CP 55,940 (24 h after CFA injection) in the inflamed paw resulted in time-dependent reduction in PWF (p<0.01; before vs. 1, 3, 6 h post CP 55,940 injection) in both hBERK and HbA-BERK mice, while no change was seen in mice injected with vehicle, suggesting that cannabinoids attenuate inflammatory pain in SCD. In conclusion, we show that mice with SCD exhibit nociceptive behaviors and hyperalgesia similar to pain characteristics in human SCD. It is likely that vasculopathy and inflammation in SCD lead to alterations in nerve structure and nociceptor sensitization, causing enhanced pain sensitivity. Importantly, we show that low doses of the cannabinoid receptor agonist CP 55,940 attenuate tonic hyperalgesia as well as inflammatory pain in a mouse model of SCD. We speculate that cannabinoids may be effective analgesics for pain in SCD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide

Life Sciences ◽  
2009 ◽  
Vol 85 (9-10) ◽  
pp. 351-356 ◽  
Author(s):  
Gláucia Maria Lopes Reis ◽  
Daniela Pacheco ◽  
Andréa Castro Perez ◽  
André Klein ◽  
Marina Abadia Ramos ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Antinociceptive Action ◽  
Cgmp Pathway

scholarly journals Cannabinoids on the Brain

2002 ◽  
Vol 2 ◽  
pp. 632-648 ◽  
Author(s):  
Andrew J. Irving ◽  
Mark G. Rae ◽  
Angela A. Coutts
Keyword(s):  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Medicinal Uses ◽  
Cellular Targets ◽  
Analgesic Effects ◽  
Current State ◽  
History Of ◽  
New Type ◽  
Reward Pathways ◽  
The Brain

Cannabis has a long history of consumption both for recreational and medicinal uses. Recently there have been significant advances in our understanding of how cannabis and related compounds (cannabinoids) affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB1and CB2, with CB1receptors mediating most of the central actions of cannabinoids. The presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system (CNS) regions and, in particular, the role of the endogenous brain cannabinoid (endocannabinoid) system. Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory; in the basal ganglia they modulate locomotor activity and reward pathways; in the hypothalamus they have a role in the control of appetite. Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain. These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders.

Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels

Life Sciences ◽  
2011 ◽  
Vol 88 (15-16) ◽  
pp. 653-657 ◽  
Author(s):  
Gláucia Maria Lopes Reis ◽  
Marina Abadia Ramos ◽  
Daniela da Fonseca Pacheco ◽  
André Klein ◽  
Andréa Castro Perez ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
K Channels ◽  
Endogenous Cannabinoid

Neuroprotective and brain edema-reducing efficacy of the novel cannabinoid receptor agonist BAY 38-7271

2003 ◽  
Vol 989 (1) ◽  
pp. 99-111 ◽  
Author(s):  
Frank Mauler ◽  
Volker Hinz ◽  
Karl-Heinz Augstein ◽  
Marion Faßbender ◽  
Ervin Horváth
Keyword(s):  
Brain Edema ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
The Novel

scholarly journals Cannabinoid Receptor Agonist WIN55, 212-2 Adjusts Lipid Metabolism in a Rat Model of Cardiac Arrest

2020 ◽  
Vol 10 (4) ◽  
pp. 192-203 ◽  
Author(s):  
Yan Xiao ◽  
Daniel Contaifer ◽  
Weiping Huang ◽  
Jin Yang ◽  
Zhangle Hu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Lipid Metabolism ◽  
Rat Model ◽  
Receptor Agonist ◽  
Cannabinoid Receptor
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