The c-kit signaling pathway is involved in the development of persistent pain

Sun, Yan; Gracias, Neilia G.; Drobish, Julie K.; Vasko, Michael R.; Gereau, Robert W.; Chen, Zhou Feng

doi:10.1016/j.pain.2009.04.011

Cited by 18 publications

(23 citation statements)

References 34 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Appropriate execution of this process depends on the structural integrity and electrophysiological properties of the intestinal neurons involved, which are in turn controlled by the SCF/c-Kit axis: SCF is constitutively expressed in various regions of the NS including the CNS, ENS and ANS, but specific expression levels are influenced by external stimuli (54). SCF directly affects neurotransmission by binding its receptor c-Kit and this influences the efficacy of the NS response to external stimuli (12). Indeed, experimental studies in a depression mouse model revealed a correlation between decreased c-Kit expression in the hippocampus and impaired neuronal differentiation and migration (55).…”

Section: Relationship Between the Scf/c-kit Axis And Neuroendocrine-imentioning

confidence: 99%

“…The system composed of SCF and its cognate receptor, c-Kit, is a principal regulator of survival and functionality for a multitude of neural crest-derived cell types, in particular for those involved in visceral perception, smooth muscle contraction and inflammation (12–14). Disorders of the neuro-endocrine-immunological network resulting from alterations in the SCF/c-Kit system provide an explanation for the high visceral sensitivity, abnormal bowel contraction strength and low-grade inflammation experienced in IBS, suggesting that this system may be an important target for intervention (15,16).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

Chai

Huang

Tang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a functional bowel disease with a complicated etiopathogenesis, often characterized by gastrointestinal motility disorder and high visceral sensitivity. IBS is a comprehensive multi-systemic disorder, with the interaction of multiple factors, such as mental stress, intestinal function and flora, heredity, resulting in the disease. The existence of a common mechanism underlying the aforementioned factors is currently unknown. The lack of therapies that comprehensively address the disease symptoms, including abdominal pain and diarrhea, is a limitation of current IBS management. The current review has explored the role of the SCF/c-Kit receptor/ligand system in IBS. The SCF/c-Kit system constitutes a classical ligand/receptor tyrosine kinase signaling system that mediates inflammation and smooth muscle contraction. Additionally, it provides trophic support to neural crest-derived cell types, including the enteric nervous system and mast cells. The regulation of SCF/c-Kit on the interstitial cells of Cajal (ICC) suggest that it may play a key role in the aberrant intestinal dynamics and high visceral sensitivity observed in IBS. The role of the SCF/c-Kit system in intestinal motility, inflammation and nerve growth has been reported. From the available biomedical evidence on the pathogenesis of IBS, it has been concluded that the SCF-c-Kit system is a potential therapeutic target for rational drug design in the treatment of IBS.

show abstract

Section: Relationship Between the Scf/c-kit Axis And Neuroendocrine-imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

Chai

Huang

Tang

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Thus c-Kit W-v mice exhibited reduced pain behavior in the second phase of the formalin test but showed anomalous persistent, increased mechanical hypersensitivity on the contralateral side after exposure to sciatic nerve chronic constriction injury, a phenomenon not seen in control animals [54]. This murine model cannot be strictly compared to that used by us in our earlier study; those mice carried complete loss-of-function c-Kit alleles, but lethality was reversed by an erythropoietin transgene that rescued c-Kit function in blood cells [31].…”

Section: Discussionmentioning

confidence: 83%

“…A recent study with c-Kit W-v mice that carry a hypomorphic c-Kit allele, in which the kinase activity of c-Kit was reduced by 80%, indicated that c-Kit might play a role in inflammatory and neuropathic pain [54]. Thus c-Kit W-v mice exhibited reduced pain behavior in the second phase of the formalin test but showed anomalous persistent, increased mechanical hypersensitivity on the contralateral side after exposure to sciatic nerve chronic constriction injury, a phenomenon not seen in control animals [54].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

Čeko

Milenkovic

Coutre

et al. 2014

Pain

View full text Add to dashboard Cite

a b s t r a c tThe tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRa, and PDFGFRb, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age-and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.Ó

show abstract

“…7 SCF/c-kit is a principal regulator for survival and function of a multitude of neural crest-derived cell types, particularly for those involved in smooth muscle contraction and inflammation. [8][9][10] Our previous study found that peripheral serum SCF/c-kit levels increase in pre-hypertensive and hypertensive patients. 11 However, the relationship between SCF/c-kit and the type of hypertension (dipper or non-dipper)…”

mentioning

confidence: 95%

Plasma SCF/c-kit Levels in Patients with Dipper and Non-Dipper Hypertension

Zhong

Chen

et al. 2017

Chinese Medical Sciences Journal

View full text Add to dashboard Cite

Objective The aim of this study was to investigate the relationship between peripheral plasma stem cell factor (SCF)/c-kit levels and the types of dipper and non-dipper hypertension in hypertensive patients.Methods This cross-sectional study included newly diagnosed hypertensive patients who underwent 24-hour ambulatory blood pressure monitor (ABPM) between January 2009 and 2012 in Jiangning city. Patients were divided into the dipper group and the non-dipper group according to ABPM measurements. The levels of SCF and its receptor c-kit, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in peripheral blood were measured via enzyme-linked immunosorbent assays. The serum levels of glucose and lipid were examined as well. The levels of SCF/c-kit were compared between the dippers and the non-dippers; and their correlation with 24-hour mean systolic blood pressure (MSBP), 24-hour mean diastolic blood pressure (MDBP), TNF-α and IL-6 were investigated using linear regression analyses statistically.Results A total of 247 patients with newly diagnosed hypertension were recruited into the study, including 116 non-dippers and 131 dippers. The levels of peripheral plasma SCF were higher in non-dipper group (907.1±52.7 ng/L vs. 778.7±44.6 ng/L; t=2.837, P<0.01), and the levels of c-kit were higher in non-dipper group too (13.2±1.7 μg/L vs 9.57±1.4 μg/L; t=2. 831, P<0.01). Linear regression analysis revealed that SCF/ckit levels were significantly positively correlated with MSBP, MDBP, plasma TNF-α, and IL-6 levels (all P<0.01).Conclusions Peripheral plasma SCF/c-kit levels are higher in patients with non-dipper hypertension than those with dipper one, and significantly correlate with 24-hour MSBP, 24-hour MDBP, serum TNF-α and IL-6 levels.

show abstract

The c-kit signaling pathway is involved in the development of persistent pain

Cited by 18 publications

References 34 publications

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

Plasma SCF/c-kit Levels in Patients with Dipper and Non-Dipper Hypertension

Contact Info

Product

Resources

About