Mast cells: Versatile gatekeepers of pain

Chatterjea, Devavani; Martinov, Tijana

doi:10.1016/j.molimm.2014.03.001

Cited by 90 publications

(81 citation statements)

References 91 publications

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“…Stimulated MCs secrete vasoactive and proinflammatory mediators, such as the preformed heparin, histamine, serotonin, proteases (e.g., tryptase), and TNF, as well as the de novo synthesized leukotrienes, prostaglandins, and cytokines (IL-1, IL-6, IL-8, TNF). At least histamine, prostaglandin D 2 (PDG 2 ), and tryptase are known to stimulate sensory nerves and elicit pain (Dai et al, 2004;Chatterjea and Martinov, 2015). In addition, histamine, PGD 2 , IL-6, TNF, and tryptase could also stimulate microglia, as well as CRH release from the hypothalamus (Turnbull and Rivier, 1999).…”

Section: Discussionmentioning

confidence: 99%

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

Tsilioni

Russell

Stewart

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain affecting more women than men. Even though clinical studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or reliable objective markers has hampered development of effective treatments. Here we report that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP), and SP-structurally-related hemokinin-1 (HK-1) were significantly (P 5 0.026, P , 0.0001, and P 5 0.002, respectively) elevated (0.82 6 0.57 ng/ml, 0.39 6 0.18 ng/ml, and 7.98 6 3.12 ng/ml, respectively) in the serum of patients with FMS compared with healthy controls (0.49 6 0.26 ng/ml, 0.12 6 0.1 ng/ml, and 5.71 6 1.08 ng/ml, respectively). Moreover, SP and HK-1 levels were positively correlated (Pearson r 5 0.45, P 5 0.002) in FMS. The serum concentrations of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF) were also significantly (P 5 0.029 and P 5 0.006, respectively) higher (2.97 6 2.35 pg/ml and 0.92 6 0.31 pg/ml, respectively) in the FMS group compared with healthy subjects (1.79 6 0.62 pg/ml and 0.69 6 0.16 pg/ml, respectively). In contrast, serum IL-31 and IL-33 levels were significantly lower (P 5 0.0001 and P 5 0.044, respectively) in the FMS patients (849.5 6 1005 pg/ml and 923.2 6 1284 pg/ml, respectively) in comparison with healthy controls (1281 6 806.4 pg/ml and 3149 6 4073 pg/ml, respectively). FMS serum levels of neurotensin were not different from controls. We had previously shown that CRH and SP stimulate IL-6 and TNF release from mast cells (MCs). Our current results indicate that neuropeptides could stimulate MCs to secrete inflammatory cytokines that contribute importantly to the symptoms of FMS. Treatment directed at preventing the secretion or antagonizing these elevated neuroimmune markers, both centrally and peripherally, may prove to be useful in the management of FMS.

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Section: Discussionmentioning

confidence: 99%

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

Tsilioni

Russell

Stewart

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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“…Chemical mediators released from mast cells through degranulation activate nociceptors that can conversely release mediators to activate mast cells when injured [28,29] . When compared to wild-type (WT) mice, mast cell-deficient mice exhibit hypo-responsive hind paws in the presence of heat and mechanical stimulus [30] . The mast cell-dependent nociceptive response has been reported to be related to histamine signaling [31] .…”

Section: Discussionmentioning

confidence: 99%

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

et al. 2016

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Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg -1 ·d -1 ) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxelstimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxeltreated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and demonstrate the therapeutic potential of quercetin for treating this side effect.

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“…It has been suggested that MCs may be involved in FMS (Lucas et al, 2006;Pollack, 2015) as well as other comorbid conditions (Theoharides, 2013a). MCs have been increasingly associated with inflammation (Galli et al, 2008;Theoharides et al, 2012a) and pain (Heron and Dubayle, 2013;Chatterjea and Martinov, 2015). The number of MCs was significantly increased in the papillary dermis of FMS patients (Blanco et al, 2010).…”

Section: Pathogenesismentioning

confidence: 99%

Fibromyalgia Syndrome in Need of Effective Treatments

Theoharides

Tsilioni

Arbetman

et al. 2015

J Pharmacol Exp Ther

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Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

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Mast cells: Versatile gatekeepers of pain

Cited by 90 publications

References 91 publications

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

Fibromyalgia Syndrome in Need of Effective Treatments

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