Abstract
Introduction: Rheumatoid arthritis (RA) is an autoinflammatory condition characterised by painful and chronically inflamed joints. Dysregulation of the immune system leads to elevated concentrations of proinflammatory cytokines
which contribute to disease pathogenesis and neuropathic pain. The endocannabinoid receptor system (ES) is primarily found in the immune and nervous systems and is known to have potential as a therapeutic target.
Cannabidiol (CBD) is a natural compound, with few adverse effects that target the ES. CBD is a non-psychoactive phytocannabinoid that possesses analgesic, neuroprotective and anti-inflammatory effects. It could serve as an effective treatment to suppress inflammation and pain simultaneously in RA. The mechanisms that underpin the relationship between inflammation, pain signalling and the ES are poorly understood. Here, we propose a study of
the analgesic potential of CBD using in vitro and in silico methods.
Methods: A pathway map and predictive model of RA pathophysiology. was generated from primary literature using the CellDesigner and COPASI software tools. Human iPSC derived sensory neuron and neuroblastoma cell line will be
cultured and lipopolysaccharide (LPS) used to induce an inflammatory challenge. CBD will be administered at a range of doses in order to study its anti-inflammatory potential. Initially, LPS doses will be optimised in neuronal culture
experiments. Next, a series of CBD dose-response experiments will be conducted to quantify any changes in intracellular or extracellular cytokine expression by Real-Time PCR and ELISA, respectively. This data will be used to
calibrate ours in silico pathway maps and models. Ultimately this pathway model will also be used to provide preclinical evidence of CBD’s effects beyond neuronal cells.
Approach for statistical analysis: Statistical analysis package SPSS (version 24) will be used to analyse the different treatment doses in challenged and control cells. One-way ANOVA will be used initially, followed by paired student Ttest
(two tail distribution) to establish if there is a statistically significant difference between treatment and control replicates.
which contribute to disease pathogenesis and neuropathic pain. The endocannabinoid receptor system (ES) is primarily found in the immune and nervous systems and is known to have potential as a therapeutic target.
Cannabidiol (CBD) is a natural compound, with few adverse effects that target the ES. CBD is a non-psychoactive phytocannabinoid that possesses analgesic, neuroprotective and anti-inflammatory effects. It could serve as an effective treatment to suppress inflammation and pain simultaneously in RA. The mechanisms that underpin the relationship between inflammation, pain signalling and the ES are poorly understood. Here, we propose a study of
the analgesic potential of CBD using in vitro and in silico methods.
Methods: A pathway map and predictive model of RA pathophysiology. was generated from primary literature using the CellDesigner and COPASI software tools. Human iPSC derived sensory neuron and neuroblastoma cell line will be
cultured and lipopolysaccharide (LPS) used to induce an inflammatory challenge. CBD will be administered at a range of doses in order to study its anti-inflammatory potential. Initially, LPS doses will be optimised in neuronal culture
experiments. Next, a series of CBD dose-response experiments will be conducted to quantify any changes in intracellular or extracellular cytokine expression by Real-Time PCR and ELISA, respectively. This data will be used to
calibrate ours in silico pathway maps and models. Ultimately this pathway model will also be used to provide preclinical evidence of CBD’s effects beyond neuronal cells.
Approach for statistical analysis: Statistical analysis package SPSS (version 24) will be used to analyse the different treatment doses in challenged and control cells. One-way ANOVA will be used initially, followed by paired student Ttest
(two tail distribution) to establish if there is a statistically significant difference between treatment and control replicates.
| Original language | English |
|---|---|
| Title of host publication | Brain and Neuroscience Advances |
| Subtitle of host publication | BNA Festival of Neuroscience 2019 |
| Publisher | SAGE Publications |
| Chapter | Novel treatments & translational neuroscience |
| Volume | 3 |
| DOIs | |
| Publication status | Published (in print/issue) - 23 May 2019 |
Keywords
- Endocannnabinoid
- Arthritis
- Neurons
- Inflammation
