Abstract:
:Because the treatment and management of neuropathic pain are extremely complicated, the characterization of novel analgesics and neuroprotectors with safe toxicological profiles is a crucial need to develop efficient therapies. Several investigations revealed that the natural neurosteroid allopregnanolone (AP) exerts analgesic, neuroprotective, antidepressant and anxiolytic effects. These effects result from AP ability to modulate GABA(A), glycine, L- and T-type calcium channels. It has been shown that AP treatment induced beneficial actions in humans and animal models with no toxic side effects. In particular, a multi-parametric analysis revealed that AP efficiently counteracted chemotherapy-evoked neuropathic pain in rats. It has also been demonstrated that the modulation of AP-producing enzyme, 3α-hydroxysteroid oxido-reductase (3α-HSOR), in the spinal cord regulates thermal and mechanical pain thresholds of peripheral nerve injured neuropathic rats. The painful symptoms were exacerbated by intrathecal injections of provera (pharmacological inhibitor of 3α-HSOR) which decreased AP production in the spinal cord. By contrast, the enhancement of AP concentration in the intrathecal space induced analgesia and suppression of neuropathic symptoms. Moreover, in vivo siRNA-knockdown of 3α-HSOR expression in healthy rat dorsal root ganglia increased thermal and mechanical pain perceptions while AP evoked a potent antinociceptive action. In humans, blood levels of AP were inversely associated with low back and chest pain. Furthermore, oral administration of AP analogs induced antinociception. Altogether, these data indicate that AP, which possesses a high therapeutic potential and a good toxicological profile, may be used to develop effective and safe strategies against chronic neuropathic pain.
journal_name
Prog Neurobioljournal_title
Progress in neurobiologyauthors
Patte-Mensah C,Meyer L,Taleb O,Mensah-Nyagan AGdoi
10.1016/j.pneurobio.2013.07.004subject
Has Abstractpub_date
2014-02-01 00:00:00pages
70-8eissn
0301-0082issn
1873-5118pii
S0301-0082(13)00066-Xjournal_volume
113pub_type
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journal_title:Progress in neurobiology
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abstract::Glutamate is a potent candidate of the excitatory transmitter at the invertebrate NMJ and the synapse of the vertebrate CNS. But pharmacological studies have not been enough to prove that glutamate functions as an excitatory neurotransmitter. During the past 10 years, we have been studying the effects of various compo...
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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doi:10.1016/j.pneurobio.2009.10.015
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journal_title:Progress in neurobiology
pub_type: 杂志文章,评审
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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doi:10.1016/j.pneurobio.2017.03.010
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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doi:10.1016/j.pneurobio.2018.04.005
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abstract::There has been an abundance of literature devoted to the involvement of noradrenaline in basic rapid eye movement (REM) sleep processes since the subject was first investigated in 1964. Nowadays, the great majority of studies highlight the need for silence in the locus coeruleus noradrenergic neurons as a condition fo...
journal_title:Progress in neurobiology
pub_type: 历史文章,杂志文章,评审
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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abstract::Coherent high-frequency neuronal activity has been proposed as a physiological indicator of perceptual and higher cognitive processes. Some of these processes can only be investigated in humans and the use of non-invasive recording techniques appears to be a prerequisite for investigating their physiological substrate...
journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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journal_title:Progress in neurobiology
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doi:10.1016/j.pneurobio.2011.03.004
更新日期:2011-06-01 00:00:00
abstract::(1) The availability of short amino acid sequences of the naturally occurring ACTH 1-39 molecule has made it possible to separate the corticotropic characteristics of the parent molecule from its neurotrophic effects. Potent neurotrophic fragments are ACTH 4-10, an analog of ACTH 4-9 (Org 2766), and alpha-MSH (ACTH 1-...
journal_title:Progress in neurobiology
pub_type: 杂志文章,评审
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更新日期:1989-01-01 00:00:00
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journal_title:Progress in neurobiology
pub_type: 杂志文章,评审
doi:10.1016/j.pneurobio.2006.06.004
更新日期:2006-06-01 00:00:00