Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-κB in a rat model of neuropathic pain

Zhu, Jing; Wei, Xiaowei; Feng, Xiaomei; Shi, Juan; Hu, Yimin; Xu, Jianguo

doi:10.1016/j.neulet.2007.12.037

Cited by 37 publications

(22 citation statements)

References 26 publications

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“…Mirtazapine administration decreased NF-B activity while it increased IL-10 levels in the right hemisphere [29]. Furthermore, mirtazapine treatment showed significant anti-nociceptive effects in the operated rats [28,29].…”

Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 89%

“…The reductions were reversed by both an adrenergic antagonist and a serotonergic antagonist, suggesting that mirtazapine reduced the cytokine production through affecting adrenergic and serotonergic systems [28]. Mirtazapine administration decreased NF-B activity while it increased IL-10 levels in the right hemisphere [29]. Furthermore, mirtazapine treatment showed significant anti-nociceptive effects in the operated rats [28,29].…”

Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 97%

“…Oral administration of mirtazapine, a tetracyclic antidepressant, for 14 days decreased the rise in protein levels of IL-1 and TNF-in the hippocampus [28] and in the right hemisphere [29] of rats with neuropathic pain caused by L5 spinal nerve transection. The reductions were reversed by both an adrenergic antagonist and a serotonergic antagonist, suggesting that mirtazapine reduced the cytokine production through affecting adrenergic and serotonergic systems [28].…”

Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 98%

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Antidepressants and Neuroinflammation: Can Antidepressants Calm Glial Rage Down?

Hashioka

2011

MRMC

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Neuroinflammation is traditionally defined as the brain's innate immune response and is also considered to be a glial-cell propagated inflammation. Increasing evidence indicates that neuroinflammation plays an important role in some cases of major depression and also that antidepressants possess anti-neuroinflammatory properties. Inhibition of neuroinflammation may represent a novel mechanism of action of antidepressant treatment. In vivo studies with animal models of neurological conditions have shown that various types of antidepressants exert inhibitory effects on the expression of inflammatory mediators, including cytokines, as well as on both microgliosis and astrogliosis in the inflamed CNS. In vitro studies using pathologically activated rodent microglia or mixed glial cells have demonstrated that various types of antidepressants diminish glial generation of inflammatory molecules. One of the most plausible mechanisms of such anti-neuroinflammatory efficacy of the drugs, as well as their antidepressant actions, seems to involve elevated intracellular cAMP levels. But the exact mechanism has still to be elucidated.

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Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 89%

Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 97%

Section: Effects Of Antidepressants On Inflam-matory Mediators In Thementioning

confidence: 98%

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Antidepressants and Neuroinflammation: Can Antidepressants Calm Glial Rage Down?

Hashioka

2011

MRMC

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“…116 However, in a double-blind, cross-over study in humans, mianserin showed no analgesic effect in patients with diabetic neuropathy. 117 Similarly, mirtazapine, an analogue of mianserin, was effective in a rat model of neuropathic pain 118 but was not found efficacious in patients with chronic pain with concomitant depression, although it was well tolerated. 119 Presently, mirtazapine is being studied (Phase 4) in fibromylagia and chronic pain (clinicalTrials.gov identifier NCT00919295, NCT01119924).…”

Section: Miscellaneous Antidepressants As Analgesicsmentioning

confidence: 99%

Efficacy of Antidepressants as Analgesics: A Review

Dharmshaktu¹,

Tayal²,

Kalra³

2012

The Journal of Clinical Pharma

275

189

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Persistent pain disorders are usually not adequately alleviated by nonsteroidal anti‐inflammatory drugs or other simple analgesics. Use of antidepressants as adjuvant therapy for the control of persistent pain is currently being practiced in disorders such as fibromyalgia, neuropathic pain, rheumatoid conditions, low back pain, and headache. This review describes the various mechanisms of analgesic activity of antidepressants along with their efficacy and tolerability profiles. Meta‐analyses and clinical studies of these agents were retrieved through the use of MEDLINE, Google scholar, and Cochrane databases. Antidepressants are effective in both neuropathic and non‐neuropathic pain and have diverse mechanisms independent of their antidepressant effects. Tricyclic antidepressants (amitryptiline, nortryptiline, desipramine) are effective compounds in the treatment of neuropathic pain, fibromyalgia, low back pain, and headaches. Studies are ongoing for the dual serotonin norepinephrine reuptake inhibitors (duloxetine, venlafaxine) in several persistent pain conditions and these may be recommended in neuropathic pain, migraines, and fibromyalgia. Evidence suggests that although the analgesic effects of selective serotonin reuptake inhibitors (fluoxetine, paroxetine, citalopram) are limited and inconsistent, yet they have a superior tolerability profile compared with tricyclic antidepressants.

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“…The tissue level of TNF-a may not correspond to the level of free TNF-a, which is actually biologically active and binds to its receptor. It is also possible that the antinociceptive effect in the CCI rats could be due to modulation of supraspinal TNF-a levels Zhu et al, 2008). One other possibility is that the antinociceptive effect of ibudilast in peripheral neuropathic rats could be through additional mechanisms, such as increasing tissue content of interleukin-10, which by itself has demonstrated antinociceptive effects in rat models of peripheral neuropathic pain Mizuno et al, 2004).…”

mentioning

confidence: 99%

The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

Hama

Broadhead²,

Lorrain³

et al. 2012

Journal of Neurotrauma

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Ibudilast, an asthma drug, has demonstrated antinociceptive effects in several rat models of peripheral neuropathic pain, and a proposed mechanism of action is the inhibition of release of the cytokine tumor necrosis factor-α (TNF-α) from activated spinal microglia. Spinal glial activation has also been demonstrated in rat models of central neuropathic pain following spinal cord injury (SCI). The current study evaluated the effect of a short course of treatment with ibudilast on SCI-induced pain, and for comparison, following a chronic constriction injury (CCI; the Bennett model) of the sciatic nerve in rats. The effects of ibudilast treatment on spinal (SCI and CCI rats), and nerve tissue (CCI only) TNF-α content were also evaluated. Following an acute midthoracic SCI with a microvascular clip (20-g force), hindpaw withdrawal thresholds were significantly decreased, indicating below-level cutaneous tactile hypersensitivity. Likewise, unilateral loose ligation of the sciatic nerve led to a robust ipsilateral tactile hypersensitivity. Rats were treated with either ibudilast (10 mg/kg IP) or vehicle (2 mL/kg) during the period of robust and steady hindpaw hypersensitivity for each model--CCI rats were treated 14-16 days post-surgery, and SCI rats were treated 30-32 days post-surgery--and tested daily. Ibudilast ameliorated hindpaw hypersensitivity in both SCI and CCI rats, whereas vehicle treatment had no effect. Interestingly, repeated treatment led to increased baseline thresholds, beyond the duration of the drug half-life, suggesting persistent changes in neuropathic pain processing. In SCI rats, an increase in TNF-α content in spinal tissue rostral to the SCI was observed. Ibudilast treatment did not significantly alter this increase. In rats with a CCI, TNF-α content was markedly increased in the ipsilateral sciatic nerve and was partially reduced following ibudilast, but not vehicle, treatment. Ibudilast could be useful for the treatment of neuropathic pain of central as well as peripheral origin.

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Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-κB in a rat model of neuropathic pain

Cited by 37 publications

References 26 publications

Antidepressants and Neuroinflammation: Can Antidepressants Calm Glial Rage Down?

Antidepressants and Neuroinflammation: Can Antidepressants Calm Glial Rage Down?

Efficacy of Antidepressants as Analgesics: A Review

The Antinociceptive Effect of the Asthma Drug Ibudilast in Rat Models of Peripheral and Central Neuropathic Pain

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