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Tumor necrosis factor receptor type‐1 in sensory neurons contributes to induction of chronic enhancement of inflammatory hyperalgesia in rat
Author(s) -
Parada Carlos A.,
Yeh Jenny J.,
Joseph Elizabeth K.,
Levine Jon D.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02626.x
Subject(s) - hyperalgesia , tumor necrosis factor alpha , inflammation , pharmacology , chemistry , medicine , cytokine , receptor , carrageenan , nociception , endocrinology , immunology
Carrageenan‐induced inflammatory pain lasting hours to days produces a protein kinase C epsilon (PKCɛ)‐dependent ‘primed’ state lasting several weeks, during which time injection of prostaglandin E 2 induces hyperalgesia which is markedly enhanced and prolonged compared to PGE 2 ‐induced hyperalgesia in normal ‘unprimed’ rats. In the present study, we demonstrate that while inhibition of prostaglandin synthesis and antagonism of β 2 ‐adrenergic receptors markedly attenuated the hyperalgesia induced by carrageenan, these interventions did not affect hyperalgesic priming. Tumor necrosis factor‐α (rat recombinant; rrTNFα), another mediator of carrageenan‐induced inflammation, alone produced hyperalgesia and priming, which were attenuated and prevented, respectively, by intrathecal administration of antisense to PKCɛ. Inhibition of TNFα with thalidomide or a rat polyclonal anti‐TNFα 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 rrTNFα‐induced priming. Acute hyperalgesia induced by carrageenan or rrTNFα 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 TNFα, which is generated during acute inflammation, can act on sensory neurons to induce hyperalgesic priming by activating neuronal PKCɛ.