title: Spinal brain-derived neurotrophic factor governs neuroplasticity and recovery from cold-hypersensitivity following dorsal rhizotomy.
abstract: Brain-derived neurotrophic factor (BDNF) has multiple effects on tropomyosin-related receptor kinase B--(TrkB) expressing neurons, including potentiation of spinal nociceptive transmission and stimulation of axon outgrowth. BDNF is upregulated in the spinal cord following dorsal root injury (DRI), a manipulation which elicits both pain and collateral sprouting. Transection of the C7 and C8 dorsal roots (C7/8 DRI) generates cold pain in the ipsilateral forepaw which peaks at 10 days, and resolves within three weeks after injury. In the present study, we investigated the influence of chronic BDNF sequestration, by intrathecal delivery of TrkB-Fc, on the plasticity of nociceptive circuitry and resultant cold pain behaviour following spinal deafferentation. C7/8 DRI resulted in a pronounced deafferentation of the C7 dorsal horn and significant depletion of both peptidergic- and non-peptidergic nociceptive projections. While changes in GAP-43 expression revealed that endogenous BDNF was exerting an overall plasticity-promoting influence on intraspinal axons after DRI, continuous TrkB-Fc treatment stimulated sprouting of nociceptive terminals. DRI stimulated a BDNF-dependent increase in the density of GABAergic interneuronal processes, as indicated by increased vesicular GABA transporter--(VGAT) and neuropeptide Y--(NPY) positive terminal densities. Finally, chronic TrkB-Fc treatment prevented cold pain resolution. These findings demonstrate that endogenous BDNF has both plasticity-promoting and plasticity-suppressing effects on the intrinsic spinal components of nociceptive circuitry, which are likely to underlie cold pain behaviour following C7/8 DRI.
authors.affiliation: ICORD (International Collaboration on Repair Discoveries), The University of British Columbia, Room 2469, Biosciences Building, 6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4 Neurorestoration Group, Wolfson Centre for Age-Related Diseases, Wolfson Wing, Hodgkin Building, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
authors.forename: Lesley J J
authors.initials: LJJ
authors.lastname: Soril
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Ramer
authors.forename: Lowell T
authors.initials: LT
authors.lastname: McPhail
authors.forename: Timothy K Y
authors.initials: TKY
authors.lastname: Kaan
authors.forename: Matt S
authors.initials: MS
authors.lastname: Ramer
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000503:physiopathology* / Q000601:surgery*; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D019051:Rhizotomy
chemical_list: D019208:Brain-Derived Neurotrophic Factor