The dissipation of neuropathic pain paradoxically involves the presence of tumor necrosis factor-? (TNF)

Ignatowski, Tracey A.; Sud, Reeteka; Reynolds, Jessica L.; Knight, Paul R.; Spengler, Robert N.

doi:10.1016/j.neuropharm.2004.11.001

Cited by 31 publications

(50 citation statements)

References 48 publications

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“…Likewise, enhanced TNFα-inhibition of NE release during peak hyperalgesia in the CCI model transforms to facilitation upon treatment of pain with amitriptyline or during the natural dissipation of hyperalgesia (Ignatowski et al, 2005). Both the inhibition and the facilitation of NE release by TNFα are dependent upon continual functioning of the α 2 -adrenergic receptor (Covey et al, 2000;Ignatowski and Spengler, 1994;Ignatowski et al, 2005). Regulation of NE release by TNFα and the α 2 -adrenergic autoreceptor are, therefore, reciprocally permissive, and adapt to modifications in each response.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of NE release by TNFα from hippocampal slices from naïve rats transforms to facilitation following chronic administration of antidepressant drugs (Ignatowski and Spengler, 1994;Nickola et al, 2001;Reynolds et al, 2004a). Likewise, enhanced TNFα-inhibition of NE release during peak hyperalgesia in the CCI model transforms to facilitation upon treatment of pain with amitriptyline or during the natural dissipation of hyperalgesia (Ignatowski et al, 2005). Both the inhibition and the facilitation of NE release by TNFα are dependent upon continual functioning of the α 2 -adrenergic receptor (Covey et al, 2000;Ignatowski and Spengler, 1994;Ignatowski et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, tricyclic antidepressants, devoid of these side-effects, are commonly used to treat chronic pain (Korzeniewska-Rybicka and Plaznik, 1998;Max, 1994;McQuay et al, 1996;Otsuka et al, 2001;Tura and Tura, 1990). Recently, we elucidated an antinociceptive mechanism for tricyclic antidepressants involving α 2 -adrenergic receptor regulation of both tumor necrosis factor-α (TNFα) production and norepinephrine (NE) release (Ignatowski et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, tricyclic antidepressant drugs (desipramine, amitriptyline, zimelidine) elicit neuroplastic changes in the regulation of NE release from the hippocampus following i.p. administration to animals within time frames corresponding to the therapeutic analgesic and/or antidepressant effectiveness of these drugs (Ignatowski et al, 1996(Ignatowski et al, , 2005Ignatowski and Spengler, 1994;Nickola et al, 2001). Taken together, these findings make the hippocampus a likely region for which attention should be focused for understanding fundamental mechanisms associated with the development, dissipation, and treatment of pain.…”

Section: Introductionmentioning

confidence: 99%

“…The increased levels of TNFα in noradrenergic regions gradually decrease coincident with dissipation of hyperalgesia, returning to pre-CCI values at resolution of hyperalgesia (Covey et al, 2000;Covey et al, 2002). During the resolution of hyperalgesia, TNFα facilitates NE release in the brain counteracting the enhanced decrease in NE release by TNFα during development of hyperalgesia (Ignatowski et al, 2005). An interactive relationship occurs between inhibition of NE release by TNFα and α 2 -adrenergic agonists, and these responses transform such that both facilitate NE release during the resolution of neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

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Antinociception mediated by α2-adrenergic activation involves increasing tumor necrosis factor α (TNFα) expression and restoring TNFα and α2-adrenergic inhibition of norepinephrine release

et al. 2007

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The central component that establishes chronic pain from peripheral nerve injury is associated with increased tumor necrosis factor-α (TNFα) production in the brain. This study examined TNFα and its reciprocally permissive role with α 2 -adrenergic activation during peak and progressive decline of thermal hyperalgesia in sciatic nerve chronic constriction injury (CCI). Accumulation of TNFα mRNA (in situ hybridization) increases in the hippocampus and locus coeruleus during the onset of neuropathic pain and persists as hyperalgesia abates. Activation of α 2 -adrenergic receptors in control rats decreases TNFα mRNA accumulation in these brain regions. In contrast, during hyperalgesia, α 2 -adrenergic activation enhances TNFα mRNA accumulation. Whether this enhanced TNFα production is associated with changes in the regulation of norepinephrine (NE) release was tested. Hippocampal slices were electrically depolarized to evaluate α 2 -adrenergic and TNFα regulation of NE release. While inhibition of NE release by TNFα is maximal during peak hyperalgesia, it subsequently transforms to facilitate NE release. In addition, α 2 -adrenergic receptor activation with clonidine (0.2 mg/kg, i.p.) in CCI rats experiencing hyperalgesia restores TNFα and α 2 -adrenergic inhibition of NE release. While TNFα directs the development of hyperalgesia, it also directs its resolution. Transformed sensitivity to α 2 -adrenergic agonists during hyperalgesia demonstrates a mechanism for therapy.

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