Role of Somatostatin and Somatostatin Receptors in Pain

Kumar, Ujendra

doi:10.1002/9780470522226.ch16

Cited by 4 publications

(3 citation statements)

References 112 publications

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“…This notion is consistent with a pharmacological study by others showing that the pain-relieving effects of J-2156 are abolished in mice null for the SST4 receptor (Helyes et al, 2009). However, other somatostatin receptor subtypes are also expressed in the anatomical regions like DRGs, spinal cord and brain that are involved in the process of nociception (Bär et al, 2004, Kumar, 2009. Hence, a very minor contribution by these receptors to the observed effects of J- Finally, the work described in this thesis also shows that the SST4 receptor mediates analgesia in the state of breast cancer induced bone pain.…”

Section: Effect Of J-2156 On Perk Levels In the Lumbar Spinal Cord Ofsupporting

confidence: 90%

Establishment, optimization and characterization of a rat model of breast cancer induced bone pain

Shenoy¹

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providing me necessary infrastructure, funds and all the guidance and support required throughout my PhD candidature. I will always remain very thankful to Dr Vetter who chose me as a PhD student and provided me with a life-changing opportunity of studying in Australia. My PhD project work was conducted in Professor Smith's laboratory at Centre for Integrated Preclinical Drug Development (CIPDD/TetraQ) (Centre for Clinical Research, Faculty of Medicine). I have seen Professor Smith as a strict mentor, yet certainly one of the kindest, most compassionate and revered persons I have ever met. These years of my professional associations with Professor Smith have left deep positive imprints on me, and I will cherish them for the rest of my life. Without Professor Smith's solid support throughout my candidature, I would have never seen this day of my life. Words will never be enough to express my feelings, but all I can very genuinenly say is that I have experienced the Almighty God in Professor Smith. I am grateful to Dr Kuo for his persistent support in my candidature.

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Section: Effect Of J-2156 On Perk Levels In the Lumbar Spinal Cord Ofsupporting

confidence: 90%

Establishment, optimization and characterization of a rat model of breast cancer induced bone pain

Shenoy¹

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“…Table 2 summarizes genomic loci and associated methylation differences of the top 20 DML between low vs. high internalized stigma among adults with non-specific cLBP. These include genes that have previously been associated with pain, such as SSTR5 ( 42 ), FOXP2 ( 43 , 44 ), and IL22RA1 ( 45 ).…”

Section: Resultsmentioning

confidence: 99%

“…To our knowledge, this represents the first study correlating internalized stigma with DNAm profiles in individuals with non-specific cLBP. We report stigma-associated DNAm differences at numerous CpG sites that annotated to genes of relevance to stress and pain pathology such as SSTR5 ( 42 ), FOXP2 ( 43 , 44 ), and IL22RA1 ( 45 ). Given the high number of differentially methylated genes, we will focus this discussion on the molecular functions, enrichment pathways, and network interaction over-represented by these differentially methylated annotated genes.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

et al. 2022

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Non-specific chronic low back pain (cLBP) represents a common musculoskeletal condition with no identifiable cause. It cannot be diagnosed with conventional neuroimaging techniques such as computerized tomography (CT). The diagnostic uncertainty that characterizes non-specific cLBP can lead to stigmatizing responses from others that can become internalized Among individuals with non-specific cLBP, internalized stigma is associated with greater pain intensity and disability. Yet, no study has examined the biological mechanism linking high internalized stigma to worse outcomes in individuals with non-specific cLBP. We aimed to identify differentially methylated loci (DML), enrichment pathways, and associated network interactions among individuals with non-specific cLBP experiencing low vs. high internalized stigma. We examined DNA methylation in whole blood samples from 48 adults, ages 19–85, using reduced representation bisulfite sequencing (RRBS). After controlling for age, sex, race, and multiple testing, differentially methylated loci (DML) differed in adults with low vs. high internalized stigma by at least 10% and q < 0.01 in 3,665 CpG sites: 2,280 hypomethylated and 1,385 hypermethylated. Gene ontology (GO) analyses of the annotated genes from these sites revealed significant enrichment of 274 biological processes, 29 cellular components, and 24 molecular functions (adjusted p < 0.05). The top enriched molecular functions regulate protein binding and DNA binding of transcription factor activity. Pathway analyses indicated that many functional genomic pathways, including Hippo Signaling, Melanogenesis, and Pathways in Cancer, were enriched with differentially methylated genes. Also, there was a significant interaction between relevance pathways such as P53, mTOR, PI3K-Akt, and Wnt signaling pathways. These pathways have previously been associated with neuroinflammation, neurodegeneration, and stress-related conditions. Thus, findings point to possible stress-induced DNAm changes as the link between high levels of internalized stigma and worse outcomes in adults with non-specific cLBP.

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Origins and Neurochemical Characteristics of Porcine Intervertebral Disc Sympathetic Innervation: a Preliminary Report

2017

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Intervertebral disc diseases (IVDDs) form a group of a vertebral column disorders affecting a large number of people worldwide. It is estimated that approximately 30% of individuals at the age of 35 and approximately 90% of individuals at the age of 60 and above will have some form of disc-affecting pathological changes leading to disc herniation, prolapse and degeneration as well as discogenic pain. Here, we aimed to establish the origins and neurochemical characteristics of porcine intervertebral disc sympathetic innervation involved in pain signalling in IVDD patients. Pigs were given an injection of the Ominipaque contrast agent and Fast Blue (FB) retrograde tracer into the L4-L5 intervertebral disc and euthanized at 2, 1, and 3 months post injection. Following euthanasia, bilateral sympathetic chain ganglia (SChG) Th13 to C1 were collected. The presence, distribution and neurochemical characteristics of retrogradely labelled SChG neurons were examined. The majority (88.8%) of all FB+ cells were found in the L3-L5 SChG. Most FB+ neurons stained for dopamine beta hydroxylase (DBH); one-third to one-quarter stained for somatostatin (SOM), neuropeptide Y (NPY) or leu-enkephalin (LENK); and only a few stained for galanin (GAL). Compared with the control, the greatest decline in neurochemical immunostaining was observed 2 weeks post injection, and the lowest decline was noticed 1 month post injection. Our study, for the first time, provides insight into the complex patterns of intervertebral disc sympathetic innervation and suggests that the best time for neurochemical balance restoration therapy would be 1 month post-injury, when the neuronal concentration of all studied substances is close to the initial physiological level, thus providing favourable conditions for successful recovery.

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Role of Somatostatin and Somatostatin Receptors in Pain

Cited by 4 publications

References 112 publications

Establishment, optimization and characterization of a rat model of breast cancer induced bone pain

Establishment, optimization and characterization of a rat model of breast cancer induced bone pain

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

Origins and Neurochemical Characteristics of Porcine Intervertebral Disc Sympathetic Innervation: a Preliminary Report

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