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Tumor necrosis factor receptor type-1 in sensory neurons contributes to induction of chronic enhancement of inflammatory hyperalgesia in rat.

Authors: Parada, CA  Yeh, JJ  Joseph, EK  Levine, JD 
Citation: Parada CA, etal., Eur J Neurosci. 2003 May;17(9):1847-52.
Pubmed: (View Article at PubMed) PMID:12752784

Carrageenan-induced inflammatory pain lasting hours to days produces a protein kinase C epsilon (PKC epsilon )-dependent 'primed' state lasting several weeks, during which time injection of prostaglandin E2 induces hyperalgesia which is markedly enhanced and prolonged compared to PGE2-induced hyperalgesia in normal 'unprimed' rats. In the present study, we demonstrate that while inhibition of prostaglandin synthesis and antagonism of beta2-adrenergic receptors markedly attenuated the hyperalgesia induced by carrageenan, these interventions did not affect hyperalgesic priming. Tumor necrosis factor-alpha (rat recombinant; rrTNFalpha), another mediator of carrageenan-induced inflammation, alone produced hyperalgesia and priming, which were attenuated and prevented, respectively, by intrathecal administration of antisense to PKC epsilon. Inhibition of TNFalpha with thalidomide or a rat polyclonal anti-TNFalpha antibody attenuated carrageenan-induced hyperalgesia and prevented priming. Intrathecal administration of antisense to tumour necrosis factor receptor type-1 (TNFR1) reduced the level of TNFR1 transported toward the peripheral terminals of sensory neurons, and attenuated both carrageenan- and rrTNFalpha-induced priming. Acute hyperalgesia induced by carrageenan or rrTNFalpha remained intact in animals treated with TNFR1 antisense. Our results demonstrate that the generation of the primed state does not require production of hyperalgesia and that TNFalpha, which is generated during acute inflammation, can act on sensory neurons to induce hyperalgesic priming by activating neuronal PKC epsilon.


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RGD Object Information
RGD ID: 5130913
Created: 2011-04-14
Species: All species
Last Modified: 2011-04-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.