p38 MAPK Activation by NGF in Primary Sensory Neurons after Inflammation Increases TRPV1 Levels and Maintains Heat Hyperalgesia

Ji, Ru-Rong; Samad, Tarek A.; Jin, Shan-Xue; Schmoll, Raymond; Woolf, Clifford J.

doi:10.1016/s0896-6273(02)00908-x

Cited by 1,078 publications

(949 citation statements)

References 63 publications

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“…Interestingly, our results indicate that the reduction in TRPV1 in the DRG occurs only at the translational level. This mode of TRPV1 regulation is not unique since translational regulation of TRPV1 expression has also been reported in rat following experimentally induced inflammation of the footpad [21].…”

Section: Discussionmentioning

confidence: 60%

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Wang

Davis

Zwick³

et al. 2006

Neurobiology of Aging

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Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify proteins that might contribute to this loss of sensation. We first show using behavioral testing that thermal sensitivity in aged male and female mice is reduced. Expression of sodium channel (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in DRG and peripheral nerves of young and old male mice was then examined. Immunoblotting and RT-PCR assays showed reduced Nav1.8 levels in aged mice. No change was measured in TRPV1 mRNA levels in DRG though TRPV1 protein appeared reduced in the DRG and peripheral nerves. The GFRα3 receptor, which binds the growth factor artemin and is expressed by TRPV1-positive neurons, was also decreased in the DRG of aged animals. These findings indicate that loss of thermal sensitivity in aging animals may result from a decreased level of TRPV1 and Nav1.8 and decreased trophic support that inhibits efficient transport of channel proteins to peripheral afferents.

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Section: Discussionmentioning

confidence: 60%

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Wang

Davis

Zwick³

et al. 2006

Neurobiology of Aging

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“…Although we have not assessed pain behaviour here, this was inferred from measurements of joint swelling and worsening clinical scores, which are features that have been shown previously to correlate with indicators of pain, namely mechanical and thermal hyperalgesia, in CFA‐induced inflammation 29, 30, 34, 56. The results presented here would suggest, therefore, that tissue acidosis is not itself a primary contributor to the pain observed in the CFA‐induced arthritis model, which might perhaps explain the lack of relief from either mechanical or thermal hyperalgesia in mice lacking ASIC1, ASIC2 or ASIC3 34.…”

Section: Discussionmentioning

confidence: 99%

Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate

Wright

Husson

et al. 2018

NMR in Biomedicine

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Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1‐13C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate‐to‐pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the 13CO2/H13CO3 − ratio, in animals injected with hyperpolarized H13CO3 −, to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA‐induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid‐sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA‐induced inflammation.

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“…Immunohistochemistry was done following a method described previously [27]. Briefly, after defined survival times, control and nerve-injured rats were deeply anesthetized with ethyl ether and perfused through the ascending aorta with normal saline followed by 4% paraformaldehyde in 0.1 mol/L phosphate buffer.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…In each rat, 4-6 sections of the L5 DRG at each time-point were selected randomly. The average percentages of CXCL12-IR-and CXCR4-IR-postive cells relative to the total number of cells were obtained for each animal across the different sections, and are presented as mean ± SEM [27,29].…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Bai

Wang

et al. 2016

Neurosci. Bull.

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Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mechanism. Here, we determined that spared nerve injury (SNI) increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia (DRG) neurons and satellite glial cells. SNI also induced longlasting upregulation of CXCL12 and CXCR4 in the ipsilateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNIinduced a sustained increase in TNF-a expression in the DRG and spinal cord. Intraperitoneal injection (i.p.) of the TNF-a synthesis inhibitor thalidomide reduced the SNI-induced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection (i.t.) of the CXCR4 antagonist AMD3100, both 30 min before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. administration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the activation of ERK in the spinal cord. The mechanical hypersensitivity induced in naïve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-a might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL12/CXCR4 signaling via ERK activation contributes to the development and maintenance of neuropathic pain.

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p38 MAPK Activation by NGF in Primary Sensory Neurons after Inflammation Increases TRPV1 Levels and Maintains Heat Hyperalgesia

Cited by 1,078 publications

References 63 publications

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

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p38 MAPK Activation by NGF in Primary Sensory Neurons after Inflammation Increases TRPV1 Levels and Maintains Heat Hyperalgesia

Cited by 1,078 publications

References 63 publications

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

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Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate