Brain-derived TNFα: involvement in neuroplastic changes implicated in the conscious perception of persistent pain

Covey, William C; Ignatowski, Tracey A.; Knight, Paul R.; Spengler, Robert N.

doi:10.1016/s0006-8993(00)01965-x

Cited by 101 publications

(103 citation statements)

References 36 publications

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“…TNF has not yet been detected in spinal cord by ELISA because no appropriate ELISA yet exists for CNS tissues. However basal levels of TNF have been detected in spinal cord by bioassay (Covey et al, 2000). Furthermore, mRNA for TNF and IL-1 has been detected in cord under basal conditions (Wang et al, 1997;Hansen et al, 1999;Sweitzer et al, 1999;Le et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

et al. 2001

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Perispinal (intrathecal) injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 creates exaggerated pain states. Decreases in response thresholds to both heat stimuli (thermal hyperalgesia) and light tactile stimuli (mechanical allodynia) are rapidly induced after gp120 administration. gp120 is the portion of HIV-1 that binds to and activates microglia and astrocytes. These glial cells have been proposed to be key mediators of gp120-induced hyperalgesia and allodynia because these pain changes are blocked by drugs thought to affect glial function preferentially. The aim of the present series of studies was to determine whether gp120-induced pain changes involve proinflammatory cytokines [interleukin-1␤ (IL-1) and tumor necrosis factor-␣ (TNF-␣)], substances released from activated glia. IL-1 and TNF antagonists each prevented gp120-induced pain changes. Intrathecal gp120 produced time-dependent, site-specific increases in TNF and IL-1 protein release into lumbosacral CSF; parallel cytokine increases in lumbar dorsal spinal cord were also observed. Intrathecal administration of fluorocitrate (a glial metabolic inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced increases in spinal IL-1 protein. These results support the concept that activated glia in dorsal spinal cord can create exaggerated pain states via the release of proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

et al. 2001

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“…microinfusion mimics the chronic constriction injury model of neuropathic pain, which involves an increase in the amount of TNF in the brain (Ignatowski et al, 1999;Covey et al, 2000). Furthermore, i.c.v.…”

Section: Discussionmentioning

confidence: 99%

“…microinfusion of rrTNF enhances chronic constriction injury-induced thermal hyperalgesia (physical manifestation of neuropathic pain) in injured rats and induces thermal hyperalgesia in naive animals (Ignatowski et al, 1999). Centrally mediated pain is an altered mood state associated with increased levels of TNF in the hippocampus and locus coeruleus (Ignatowski et al, 1999;Covey et al, 2000). Interestingly, pain is alleviated by antidepressants (Bryson and Wilde, 1996).…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant

Reynolds

Ignatowski²,

Sud³

et al. 2004

J Pharmacol Exp Ther

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The present study documents a role for brain-derived tumor necrosis factor-␣ (TNF) in the mechanism of action of the antidepressant drug desmethylimipramine (desipramine). To establish this role, field stimulation and superfusion of rat hippocampal slices was employed to investigate the regulation of norepinephrine (NE) release by TNF. Chronic desipramine administration transforms TNF-mediated inhibition of NE release to facilitation, dependent upon ␣ 2 -adrenergic receptor activation. Chronic i.c.v. microinfusion of polyclonal TNF antibody (pTNF-Ab) similarly transforms TNF inhibition of NE release to facilitation. To determine whether this transformation is due to desipramine-induced inhibition of TNF bioactivity in the brain, rats were i.c.v. microinfused with recombinant rat TNF (rrTNF) for 14 days, either alone or with simultaneous i.p. desipramine administration. TNF regulation of NE release in hippocampal slices isolated from these rats was compared with slices isolated from rats chronically administered desipramine alone. Although simultaneous microinfusion of rrTNF with chronic desipramine administration prevents the transformation induced by desipramine, microinfusion of rrTNF enhances TNF inhibition of NE release. These cellular events correspond to changes in immobility, analyzed by the forced swim test (FST). Intracerebroventricular microinfusion of rrTNF increases the duration of immobility of rats in the FST, compared with rats microinfused with aCSF. Desipramine administered chronically decreases immobility duration, which is mimicked by i.c.v. microinfusion of pTNF-Ab and prevented by simultaneous i.c.v. microinfusion of rrTNF. Thus, i.c.v. microinfusion of rrTNF with concomitant desipramine administration opposes decreases in neuron-associated TNF levels, required to transform presynaptic sensitivity to TNF, which is necessary for the drug to be efficacious.The etiology of depression as well as the mechanism of action of antidepressant drugs has been investigated for over 40 years, yet precise mechanisms that direct the expression of mood are unknown. Several theories have been postulated that implicate altered release of the neurotransmitter norepinephrine (NE) (Schildkraut, 1965) in the pathogenesis of depression. The classic Monoamine Theory of Depression proposes that symptoms of depression are due to an imbalance in the bioavailability of the monoamines, NE and serotonin, within the central nervous system (Schildkraut, 1965;Willner, 1985). Therefore, antidepressant drug-induced regulation of NE availability, as well as adrenergic receptors that regulate the release of NE, have been extensively investigated (Banerjee et al., 1977;Crews and Smith, 1978). A "dysregulation hypothesis" has also been proposed, which implicates an impaired negative feedback on presynaptic neurons due to dysfunctional presynaptic ␣ 2 -adrenergic receptors (Siever and Davis, 1985;Maes et al., 1999). These receptors are primary regulators of NE release from noradrenergic neurons and are classically known to ...

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“…After 14 daily injections of the stimulus (PGE 2 or dopamine), the sensitivity of the nociceptor does not return to its basal level but, instead, reaches a plateau, which persists for more than thirty days (87) . Other studies have reported that a persistent hypernociception can also be triggered by the persistent presence of stimuli (88) . In line with the PGE 2 -or dopamine-induced persistent hypernociception, it was demonstrated that repeated intraplantar injections of IL-1β, IL-8 or TNF-α also cause persistent mechanical hypernociception that is prevented by daily treatment with indomethacin and atenolol.…”

Section: Chronic Inflammatory Pain Mediated By Cytokinesmentioning

confidence: 95%

Cytokine inhibitors and pain control

Verri¹,

Cunha²,

Poole³

et al. 2007

Rev. Bras. Reumatol.

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Recebido em 17/03/07. Aprovado, após revisão, em 25/09/07. Conflits of interest: nothing to disclose. RESUMOOs autores fazem uma revisão sobre evidências que demonstram o papel de citocinas em modelos experimentais de dor, discutindo possíveis terapias com alvo em citocinas para controle da dor.Palavras-chave: hiperalgesia, dor inflamatória, citocinas, nocicepção, analgesia. ABSTRACTThe authors describe the evidences supporting the role of cytokines in experimental pain, discussing possible approaches for pain control using cytokine-targeting therapies.

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Brain-derived TNFα: involvement in neuroplastic changes implicated in the conscious perception of persistent pain

Cited by 101 publications

References 36 publications

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

Intrathecal HIV-1 Envelope Glycoprotein gp120 Induces Enhanced Pain States Mediated by Spinal Cord Proinflammatory Cytokines

Brain-Derived Tumor Necrosis Factor-α and Its Involvement in Noradrenergic Neuron Functioning Involved in the Mechanism of Action of an Antidepressant

Cytokine inhibitors and pain control

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