Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara A.; Lei, Jianxun; Gupta, Kalpna

doi:10.3324/haematol.2015.136523

Cited by 57 publications

(59 citation statements)

References 57 publications

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“…Earlier we observed that the non-selective cannabinoid receptor agonist CP 55,940 attenuates deep tissue, mechanical and thermal hyperalgesia in HbSS-BERK sickle mice [5, 20]. We therefore examined if the length and curvature measurements would complement the behavioral measures in response to CP55,940 treatment.…”

Section: Resultsmentioning

confidence: 99%

Quantification of pain in sickle mice using facial expressions and body measurements

Mittal

Gupta

Lamarre

et al. 2016

Blood Cells, Molecules, and Diseases

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Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment. The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS. We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score. CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD.

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Section: Resultsmentioning

confidence: 99%

Quantification of pain in sickle mice using facial expressions and body measurements

Mittal

Gupta

Lamarre

et al. 2016

Blood Cells, Molecules, and Diseases

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show abstract

“…In the Berkeley sickle mice, mast cell activation contributes to neurogenic inflammation, chronic pain, and Hypoxia/Reoxygenation (H/R)-evoked hyperalgesia, which were ameliorated upon treatment with mast cell inhibitor imatinib, and cannabinoids as well as nociception receptor ligand AT200 [99,100]. Systemic deletion of calpain-1 in Townes sickle mice ameliorated chronic pain behaviors including mechanical, heat, cold, and deep tissue/musculoskeletal hyperalgesia.…”

Section: Calpain 1 Therapymentioning

confidence: 99%

Non-Conventional Pain Management for Sickle Cell Disease

Al-Jafar¹

2017

Ann Hematol Oncol

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Sickle cell disease is a congenital blood disorder affecting hemoglobin molecule. It leads to a rigid, sickle like shape red blood cell. Most people with sickle cell disease have severe painful episodes called vaso-occlusive crises. However, the frequency, severity, and duration of these crises vary tremendously. The pain is classified into two types, nociception pain which is intact peripheral or central nervous system and neuropathic pain which is initiated by dysfunction of the peripheral or central nervous system. Despite the pain being the most common complication of sickle cell disease, there is a lack of novel pain treatments. Pain killers including opioid have continued to be the main stay of therapy over the past several decades. A non-conventional treatments for pain were applied effectively to avoid the serious systemic side effects of the pharmaceutical pain killers.

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“…However, patients are often recalcitrant to opioid therapy, can be denied treatment due to “opioidphobia”, or are over-treated. Recently, some critical peripheral and spinal mechanisms underlying pain have been recognized using humanized sickle mouse models (Cataldo et al, 2015, Hillery et al, 2011, Kohli et al, 2010, Valverde et al, 2016, Vincent et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease

Case

Zhang

Mundahl

et al. 2017

NeuroImage: Clinical

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Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

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Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

Cited by 57 publications

References 57 publications

Quantification of pain in sickle mice using facial expressions and body measurements

Quantification of pain in sickle mice using facial expressions and body measurements

Non-Conventional Pain Management for Sickle Cell Disease

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease

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