Steroids, spinal cord and pain sensation.

During the whole life, the nervous system is continuously submitted to the actions of different categories of hormones, including steroids. Therefore, the interactions between hormonal compounds and neural tissues are subjected to intense investigations. While a majority of studies focus on the brain, the spinal cord (SC) has received little attention, although this structure is also an important part of the central nervous system, controlling motor and sensory functions. To point out the importance of interactions between hormones and the SC in the regulation of neurobiological activities, we recapitulated and discussed herein various key data, revealing that the pivotal role played by the SC in nociception and pain modulation, directly depends on the SC ability to metabolize and synthesize steroidal molecules. The paper suggests that future investigations aiming to develop effective strategies against chronic pain, must integrate regulatory effects exerted by hormonal steroids on the SC activity, as well as the actions of endogenous neurosteroids locally synthesized in spinal neural networks.journal article2011 Oct 01importe

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL) ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days) prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in rats. The data suggest that 3α-androstanediol-based therapy may constitute an efficient strategy to explore in humans for the eradication of chemotherapy-induced peripheral neuropathy.journal articleresearch support, non-u.s. gov't20132013 11 15importe

The translocator protein ligand XBD173 improves clinical symptoms and neuropathological markers in the SJL/J mouse model of multiple sclerosis

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