In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the...
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[title] => Unexpected association of the “inhibitory” neuroligin 2 with excitatory PSD95 in
[paragraph] => Unexpected association of the “inhibitory” neuroligin 2 with excitatory PSD95 in neuropathic pain
[content] => Authors
T. Dolique, A. Favereaux, O. Roca-Lapirot, V. Roques, C. Léger et al.
Lab
Université de Bordeaux, Bordeaux, France
Journal
PAIN
Abstract
In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. In control animals, intrathecal injections of small interfering RNA (siRNA) targeting NL2 increased mechanical sensitivity, which confirmed the association of NL2 with inhibition. By contrast, siRNA application produced antinociceptive effects in SNL rats. Regarding NL partners, expression of the excitatory postsynaptic scaffolding protein PSD95 unexpectedly covaried with NL2 overexpression, and NL2/PSD95 protein interaction and colocalization increased. Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(−) isoform. Our data showed unexpected upregulation and pronociceptive effects of the “inhibitory” NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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[description_short] => A quick solution to determine the mechanical sensitivity threshold in rodents (mice and rats). Now wireless, to be free from annoying cables!
This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.


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[description_short] => As an electronic version of the classical Von Frey Filaments esthesiometer (or aesthesiometer), the latest evolution of Bioseb's Electronic Von Frey instrument for determining the mechanical sensitivity threshold in rodents (rats and mice) is a must-have instrument for your reseach on hyperalgesia and allodynia. By measuring and recording the force at which the animal exhibits a paw withdrawal reflex, pathologies related to sensory response and hyper- or hypo-aesthesia can be studied.
The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.


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