Acute Topical Application of Tumor Necrosis Factor α Evokes Protein Kinase A-Dependent Responses in Rat Sensory Neurons

Zhang, Junming; Li, Huiqing; Liu, Baogang; Brull, Sorin J.

doi:10.1152/jn.2002.88.3.1387

Cited by 104 publications

(55 citation statements)

References 30 publications

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“…Indeed, inflammatory cytokines acting locally may directly or indirectly stimulate and/or sensitize nociceptors, thereby contributing to sensory hyperalgesia (5,16). Previous work implicating TNF-␣ in the development of neuropathic pain follows the observation that exogenous TNF-␣ elicits a PKA-dependent response in rat sensory neurons (29). However, in the present study, TNF-␣ at concentrations considerably higher than that found in mesenteric lymph after LPS treatment did not stimulate mesenteric afferent discharge.…”

Section: Discussioncontrasting

confidence: 70%

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins

Wang

Glatzle

Mueller

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Bacterial translocation across the intestinal mucosal barrier leads to a macrophagemediated inflammatory response, visceral hyperalgesia, and ileus. Our aim was to examine how mediators released into mesenteric lymph following LPS treatment influence intestinal afferent sensitivity and the role played by prostanoids in any sensitization. Intestinal lymph was collected from awake rats following treatment with either saline or LPS (5 mg/kg ip). Extracellular multiunit afferent recordings were made from paravascular mesenteric nerve bundles supplying the rat jejunum in vitro following arterial administration of control lymph, LPS lymph, and LPS. Mesenteric afferent discharge increased significantly after LPS lymph compared with control lymph. Peak discharge occurred within 2 min and remained elevated for 5 to 8 min. This response was attenuated by pretreatment with naproxen (10 M), and restored upon addition of prostaglandin E 2 (5 M) in the presence of naproxen, but AH6809 (5 M), an EP 1/EP2 receptor(s) antagonist, failed to decrease the magnitude of LPS lymph-induced response. LPS itself also stimulated mesenteric afferent discharge but was unaffected by naproxen. TNF-␣ was significantly increased in LPS lymph compared with control lymph (1,583 Ϯ 197 vs. 169 Ϯ 38 pg/ml, P Ͻ 0.01) but exogenous TNF-␣ failed to evoke any afferent nerve discharge. We concluded that inflammatory mediators released from the gut into mesenteric lymph during endotoxemia have a profound effect on afferent discharge. These mediators influence afferent firing via the release of local prostaglandins. cytokines; lymph; hypersensitivity A SMALL BUT SIGNIFICANT SUBGROUP of irritable bowel syndrome (IBS) patients can trace the onset of their symptoms to a bout of acute gastroenteritis (27). It has been suggested that in these postinfectious IBS patients an acute inflammatory insult leads to the development of chronic symptoms (27, 28) and while psychosocial factors play a major role, there is evidence that an augmented inflammatory response may be a predisposing factor (12). Certainly there is a wealth of evidence demonstrating that inflammatory mediators alter the sensitivity of intestinal afferents (18). Many IBS patients exhibit a lowered visceral sensory threshold to pain; thus it is conceivable that in postinfectious IBS that visceral hypersensitivity may be secondary to an inflammatory insult (28). Understanding the etiology of chronic changes in visceral hypersensitivity may therefore be of considerable benefit to patients with postinfectious IBS.LPS from Gram-negative bacteria, also known as endotoxin, can trigger a macrophage-driven cytokine cascade that is referred to as an acute-phase response. This drives a local inflammatory reaction and generates behavioral responses known as sickness behavior that include fever, anorexia, and hyperalgesia (21). In animal models, systemic LPS can cause ileus (8), rectal hypersensitivity (5), and also produces a profound increase in the afferent discharge emanating from the bowel wall (19). The mac...

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Section: Discussioncontrasting

confidence: 70%

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins

Wang

Glatzle

Mueller

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…For example, administration of tumor necrosis factor (TNF) to DRG in rats induces cutaneous hyperalgesia to mechanical stimuli. Conversely, blocking the activity of certain inflammatory cytokines in DRG partially relieves the CCD-induced hyperalgesia [16,17] . In addition, increased activity of satellite glial cells in the DRG has been recently shown to play an important role in CCD-induced neuronal hypersensitivity [18] .…”

Section: Discussionmentioning

confidence: 99%

Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice

Chen

Kong

et al. 2011

Neurosci. Bull.

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Objective Low back pain is one of the most inextricable problems encountered in clinics. Animal models that imitate symptoms in humans are valuable tools for investigating low back pain mechanisms and the possible therapeutic applications. With the development of genetic technology in pain field, the possibility of mutating specific genes in mice has provided a potent tool for investigating the specific mechanisms of pain. The aim of the present study was to develop a mouse model of chronic compression of dorsal root ganglion (CCD), in which gene mutation can be applied to facilitate the studies of chronic pain. Methods Chronic compression of L4 and L5 dorsal root ganglia was conducted in mice by inserting fine stainless steel rods into the intervertebral foramina, one at L4 and the other at L5. Mechanical allodynia and thermal hyperalgesia were examined with von Frey filaments and radiating heat stimulator, respectively. Results The CCD mice displayed dramatic mechanical and thermal hyperalgesia as well as tactile allodynia in the hindpaw ipsilateral to CCD. In addition, this mechanical and thermal hyperalgesia as well as tactile allodynia was also found to spread to the contralateral hindpaw. Conclusion This model, combined with the possible genetic modification, will strengthen our knowledge of the underlying mechanisms of low back pain. It also favors the development of new treatment strategies for pain and hyperalgesia after spinal injury and other disorders which affect the dorsal root ganglion in humans.

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“…To inhibit PKA activity, presynaptic neurons were incubated selectively in H-89 (Calbiochem, La Jolla, CA) (Zhang et al, 2002) or KT5720 (Calbiochem) (Diefenbach et al, 2000), which were dissolved in DMSO (final [DMSO] Ͻ0.01%). 8Br-cAMP (Research Biochemicals, Natick, MA) and acetylcholine were dissolved in water.…”

Section: Methodsmentioning

confidence: 99%

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

2003

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The mechanisms by which neurons regulate the number and strength of synapses during development and synaptic plasticity have not yet been defined fully. This lack of fundamental knowledge in the fields of neurodevelopment and synaptic plasticity can be attributed, in part, to compensatory mechanisms by which neurons accommodate for the loss of function in their synaptic partners. This is generally achieved either by scaling up neuronal transmitter release capabilities or by enhancing the postsynaptic responsiveness. Here, we demonstrate that regulation of synaptic strength and number between identified Lymnaea neurons visceral dorsal 4 (VD4, the presynaptic cell) and left pedal dorsal 1 (LPeD1, the postsynaptic cell) requires presynaptic activation of a cAMP-PKA-dependent signal. Experimental activation of the cAMP-PKA pathway resulted in reduced synaptic efficacy, whereas inhibition of the cAMP-PKA cascade permitted hyperinnervation and an overall enhancement of synaptic strength. Because synaptic transmission between VD4 and LPeD1 does not require a cAMP-PKA pathway, our data show that these messengers may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity.

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Acute Topical Application of Tumor Necrosis Factor α Evokes Protein Kinase A-Dependent Responses in Rat Sensory Neurons

Cited by 104 publications

References 30 publications

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins

Lipopolysaccharide-induced changes in mesenteric afferent sensitivity of rat jejunum in vitro: role of prostaglandins

Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice

Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

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