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A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway.
Neuroscience. 2015 Sep 24; 304:240-9.N

Abstract

Intrathecal delivery of glial cell line-derived neurotrophic factor (GDNF) reverses mechanical allodynia after 5th lumbar (L5) spinal nerve ligation (SNL). However, the molecular mechanism behind this process is not fully understood. Following sciatic nerve injury, primary afferent neurons in the injured dorsal root ganglion (DRG) begin to express neuropeptide Y (NPY) that is absent in normal DRG. The aim of the current study was to determine the relationship of this de novo expression of NPY and the anti-allodynic effect of GDNF. Following L5 SNL, 73% of neurons began to express NPY mRNA in the ipsilateral L5 DRG and robust NPY-immunoreactive fibers appeared in the ipsilateral GN where the touch-sense mediating A-fiber primary afferents from the hindpaw terminate. Seven-daylong intrathecal infusion of GDNF at the L5 DRG level, starting on day three when mechanical allodynia had fully developed, reversed once-established these changes. The GN neurons normally expressed NPY Y1 receptor, but not Y2, Y4, or Y5 receptors, and L5 SNL did not change the expression pattern. Bolus intracisternal injection of BIBP3226, a Y1 receptor antagonist, dose-dependently reversed mechanical allodynia. We demonstrated that GDNF reversed once-established mechanical allodynia as well as NPY induction in the touch-sense processing pathway. NPY could facilitate touch-sense processing by Y1 receptor in the gracile nucleus after peripheral nerve injury. GDNF may exert anti-allodynic effects through mitigation of this NPY up-regulation. The effectiveness of delayed treatment further indicates the therapeutic potential of GDNF on neuropathic pain.

Authors+Show Affiliations

Department of Anatomy & Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Pain Mechanism Research Group, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Electronic address: tfukuoka@hyo-med.ac.jp.Department of Anatomy & Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26215916

Citation

Fukuoka, T, and K Noguchi. "A Potential Anti-allodynic Mechanism of GDNF Following L5 Spinal Nerve Ligation; Mitigation of NPY Up-regulation in the Touch Sense Pathway." Neuroscience, vol. 304, 2015, pp. 240-9.
Fukuoka T, Noguchi K. A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway. Neuroscience. 2015;304:240-9.
Fukuoka, T., & Noguchi, K. (2015). A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway. Neuroscience, 304, 240-9. https://doi.org/10.1016/j.neuroscience.2015.07.059
Fukuoka T, Noguchi K. A Potential Anti-allodynic Mechanism of GDNF Following L5 Spinal Nerve Ligation; Mitigation of NPY Up-regulation in the Touch Sense Pathway. Neuroscience. 2015 Sep 24;304:240-9. PubMed PMID: 26215916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway. AU - Fukuoka,T, AU - Noguchi,K, Y1 - 2015/07/26/ PY - 2015/05/26/received PY - 2015/07/16/revised PY - 2015/07/21/accepted PY - 2015/7/29/entrez PY - 2015/7/29/pubmed PY - 2016/5/25/medline KW - dorsal root ganglion KW - gracile nucleus KW - neuropathic pain KW - neuropeptide Y receptors SP - 240 EP - 9 JF - Neuroscience JO - Neuroscience VL - 304 N2 - Intrathecal delivery of glial cell line-derived neurotrophic factor (GDNF) reverses mechanical allodynia after 5th lumbar (L5) spinal nerve ligation (SNL). However, the molecular mechanism behind this process is not fully understood. Following sciatic nerve injury, primary afferent neurons in the injured dorsal root ganglion (DRG) begin to express neuropeptide Y (NPY) that is absent in normal DRG. The aim of the current study was to determine the relationship of this de novo expression of NPY and the anti-allodynic effect of GDNF. Following L5 SNL, 73% of neurons began to express NPY mRNA in the ipsilateral L5 DRG and robust NPY-immunoreactive fibers appeared in the ipsilateral GN where the touch-sense mediating A-fiber primary afferents from the hindpaw terminate. Seven-daylong intrathecal infusion of GDNF at the L5 DRG level, starting on day three when mechanical allodynia had fully developed, reversed once-established these changes. The GN neurons normally expressed NPY Y1 receptor, but not Y2, Y4, or Y5 receptors, and L5 SNL did not change the expression pattern. Bolus intracisternal injection of BIBP3226, a Y1 receptor antagonist, dose-dependently reversed mechanical allodynia. We demonstrated that GDNF reversed once-established mechanical allodynia as well as NPY induction in the touch-sense processing pathway. NPY could facilitate touch-sense processing by Y1 receptor in the gracile nucleus after peripheral nerve injury. GDNF may exert anti-allodynic effects through mitigation of this NPY up-regulation. The effectiveness of delayed treatment further indicates the therapeutic potential of GDNF on neuropathic pain. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/26215916/A_potential_anti_allodynic_mechanism_of_GDNF_following_L5_spinal_nerve_ligation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(15)00673-9 DB - PRIME DP - Unbound Medicine ER -