MiR-134/LIM Kinase1: how far can this duo modulate neuropathic pain?
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1
Alexandria University, Zoology, Egypt
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2
Bordeaux Segalen University, France
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3
Alexandria University, Biochemistry, Egypt
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4
Bordeaux1 University, France
Spinal cord lesions may induce severe neuropathic pain. While more than 8% of the world’s population suffer from neuropathic pain, the mechanisms underlying this pain remain unclear. The neuronal actin cytoskeleton is critically involved in morphological plasticity and synaptic reorganization acting as a key player in neuropathic pain mechanisms.
LIM Kinase1 (LIMK1) is a protein kinase responsible for actin polymerization by inhibiting Cofilin/ADF (Actin Depolymerisation Factor) activity. LIMK1 expression is controlled by the microRNA, MiR-134 that represses LIMK1-mRNA translation. MiR-134 is considered as a negative regulator of dendritic spine volume and LIMK1 has been reported to promote actin polymerization in dendrites. Moreover, LIMK1/cofilin regulate the insertion and trafficking of the AMPA excitatory glutamate receptors (AMPAR) at the synapse. Therefore, it is likely that miR-134/LIMK1 modulates the transmission of nociceptive information in the spinal dorsal horn.
Our objective was to investigate the effects of miR-134/LIMK1 on the reorganization of pain circuits in spinal dorsal horn and on pain sensitization.
Firstly, we investigated miR-134 distribution in the spinal dorsal horn of both sham and neuropathic animals. Then we co-detected miR-134 with different synaptic markers. We showed by qRT-PCR analysis a decrease of miR-134 expression in neuropathic animals when compared to shams which was concomitant with an increase of LIMK1. Animals have also been subjected to intrathecal injection of miR-134 knockdown (miR-134 KD) probes and functional consequences on pain behavior were studied. Interestingly, in these conditions, a significant increase in pain withdrawal threshold (less pain) was observed when tested for evoked (Von Frey test) or spontaneous (dynamic weight bearing test) pain behavior. We also demonstrated the effect of miR-134 KD transfection on the trafficking of AMPAR. Evenly, our preliminary electrophysiological recording showed a significant decrease in minis AMPA’ amplitude in the spinal cord superficial laminae after miR-134 KD intrathecal application.
Taken together, our results suggest that miR-134 down regulation in neuropathic conditions exerts an anti-nociceptive role.
Keywords:
miR-134,
LIMK1,
Spinal Cord,
neuropathic pain,
Rats
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Abdel Salam
S,
Moftah
M,
Zaky
A,
Fossat
P,
Favereaux
A and
Landry
M
(2013). MiR-134/LIM Kinase1: how far can this duo modulate neuropathic pain?.
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00001
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Received:
26 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Prof. Marc Landry, Bordeaux Segalen University, Bordeaux, France, marc.landry@u-bordeaux.fr