Mast cell degranulation mediates compound 48/80-induced hyperalgesia in mice

Chatterjea, Devavani; Wetzel, Abigail; Mack, Madison R.; Engblom, Camilla; Allen, Juliann; Mora-Solano, Carolina; Paredes, Luisa; Balsells, Evelyn; Martinov, Tijana

doi:10.1016/j.bbrc.2012.07.074

Cited by 70 publications

(98 citation statements)

References 37 publications

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“…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] . A large amount of evidence supports the notion that mast cells contribute to pain pathologies regardless of whether they occur in biomedical exploration or in clinical practice.…”

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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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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“…Place absorbent material below the stand to absorb/collect excreted waste. Allow mice to acclimate for 15 min in chambers prior to baseline or experimental withdrawal threshold assessment 6,7,10 . 5.…”

Section: General Considerations For Hind Paw Withdrawal Threshold Assmentioning

confidence: 99%

“…Continue until you have assessed withdrawal thresholds of each mouse once. Repeat another four times, so that each mouse is measured 5x as previously described 10 . 4.…”

Section: Baseline Hind Paw Withdrawal Threshold Assessmentmentioning

confidence: 99%

“…Reduction in time and intensity of previously specified responses to noxious stimuli are used to measure pain states in these animals as rodent subjects are not otherwise able to report a sensation of pain 6 . Altered responses to temperature and pressure are commonly used as metrics of tissue sensitivity in rodent models of inflammatory nociception that can be caused by infection 7,8 , chemical exposure 6,9,10 , surgical incision 11 , as well as neuropathic pain caused by nerve ligation 12 …”

Section: Introductionmentioning

confidence: 99%

“…2. Increase pressure gradually until defined nociceptive response behaviors such as hind paw retraction, hind paw licking, or four-paw jumping 6,10 are observed. Instruct the other investigator to transcribe the pressure that elicited the observed behavior.…”

Section: Baseline Hind Paw Withdrawal Threshold Assessmentmentioning

confidence: 99%

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Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

Martinov

Mack

Sykes

et al. 2013

JoVE

Self Cite

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Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen, or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models.

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Evidence for the modulation of nociception in mice by central mast cells

Kissel

Kovács

Larson

2017

European Journal of Pain

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Background Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. Methods We examined the central effect of two hyperalgesic compounds that also induce mast cell degranulation and stabilized mast cells using cromolyn. Results Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1–17) (opioid compound) each correlated with the percent of thalamic mast cells that were degranulated. Degranulation of these mast cells by the central injection of compound 48/80, devoid of neurotrophic or opioid activity, was sufficient to recapitulate thermal hyperalgesia. Stabilization of mast cells by central injections of cromolyn produced no analgesic effect on baseline tail flick or von Frey fiber sensitivity, but inhibited thermal hyperalgesia produced by compound 48/80 and tactile hyperalgesia induced by dynorphin and by Freund’s complete adjuvant. Finally, chemical nociception produced by the direct activation of nociceptors by formalin (phase I) was not inhibited by centrally injected cromolyn whereas chemical nociception dependent on central sensitization (formalin-phase II and acetic acid-induced abdominal stretches) was. Conclusions These convergent lines of evidence suggest that degranulation of centrally located mast cells sensitizes central nociceptive pathways leading to hyperalgesia and tonic chemical sensitivity.

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Mast cell degranulation mediates compound 48/80-induced hyperalgesia in mice

Cited by 70 publications

References 37 publications

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

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

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

Evidence for the modulation of nociception in mice by central mast cells

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