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Microglia Mediate Loss of Spinal Cord Inhibitory Synapses in Neuropathic Pain

48 Pages Posted: 23 Oct 2020 Publication Status: Published

See all articles by Noosha Yousefpour

Noosha Yousefpour

McGill University - Department of Pharmacology and Therapeutics

Samantha Locke

McGill University - Department of Pharmacology and Therapeutics

Chengyang Wang

McGill University - Department of Pharmacology and Therapeutics

Haley Deamond

McGill University - Department of Pharmacology and Therapeutics

Lucas Marques

McGill University - Department of Pharmacology and Therapeutics

Manon St. Louis

McGill University - Department of Pharmacology and Therapeutics

Johanne Ouellette

McGill University - Department of Pharmacology and Therapeutics

Arkady Khoutorsky

McGill University - Alan Edwards Centre for Research on Pain; McGill University - Department of Anesthesia

Yves De Koninck

McGill University - Department of Pharmacology and Therapeutics

Alfredo Ribeiro-Da-Silva

McGill University - Department of Pharmacology and Therapeutics

More...

Abstract

Spinal dorsal horn disinhibition has been implicated in neuropathic pain, a debilitating condition resulting from damage to the nervous system. Loss of dorsal horn inhibitory synapses has been proposed to contribute to the reduction of inhibitory tone in neuropathic pain. However, how nerve injury affects inhibitory synapses in relation to other synaptic populations and mechanisms mediating synaptic loss remain unknown. Using a nerve injury rodent model of neuropathic pain, we show that microglia selectively engulf synapses intrinsic to the dorsal horn, but not terminals of primary afferents. Furthermore, we reveal that microglia specifically remove complement-tagged inhibitory synapses that are presynaptic to dorsal horn interneurons and terminals of primary afferents. Inhibiting or depleting microglia prevented inhibitory synapse loss without affecting excitatory synapses and attenuated pain behaviour at chronic stages of neuropathic pain. These results define a new role for microglia in neuropathic pain pathogenesis: the selective pruning of spinal inhibitory synapses.

Keywords: Neuropathic Pain, spinal cord, Structural Plasticity, microglia, Synapse Pruning, Disinhibition

Suggested Citation

Yousefpour, Noosha and Locke, Samantha and Wang, Chengyang and Deamond, Haley and Marques, Lucas and St. Louis, Manon and Ouellette, Johanne and Khoutorsky, Arkady and Khoutorsky, Arkady and De Koninck, Yves and Ribeiro-Da-Silva, Alfredo, Microglia Mediate Loss of Spinal Cord Inhibitory Synapses in Neuropathic Pain. Available at SSRN: https://ssrn.com/abstract=3710746 or http://dx.doi.org/10.2139/ssrn.3710746
This version of the paper has not been formally peer reviewed.

Noosha Yousefpour

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Samantha Locke

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Chengyang Wang

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Haley Deamond

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Lucas Marques

McGill University - Department of Pharmacology and Therapeutics

Canada

Manon St. Louis

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Johanne Ouellette

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Arkady Khoutorsky

McGill University - Alan Edwards Centre for Research on Pain

Montreal
Canada

McGill University - Department of Anesthesia

Montreal
Canada

Yves De Koninck

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

Alfredo Ribeiro-Da-Silva (Contact Author)

McGill University - Department of Pharmacology and Therapeutics ( email )

Canada

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