Depletion of spinal 5-HT accelerates mechanosensory recovery in the deafferented rat spinal cord
| Autor: | Matt S. Ramer, Angela L. M. Scott, Jacquelyn J. Cragg |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Pain Threshold Serotonin Tyrosine 3-Monooxygenase medicine.medical_treatment Calcitonin Gene-Related Peptide Central nervous system 5 7-Dihydroxytryptamine Serotonergic Rhizotomy Hypesthesia Rats Sprague-Dawley chemistry.chemical_compound Serotonin Agents Developmental Neuroscience Neurotrophic factors Lectins Physical Stimulation medicine Animals Neuropeptide Y Serotonin Plasma Membrane Transport Proteins Mechanosensation business.industry Brain-Derived Neurotrophic Factor Brain Peripheral Nervous System Diseases Recovery of Function Spinal cord Rats Up-Regulation Disease Models Animal medicine.anatomical_structure Neurology chemistry Spinal Cord Hyperalgesia Neuropathic pain Vesicular Glutamate Transport Protein 1 Microglia business Spinal Nerve Roots Neuroscience |
| Zdroj: | Experimental neurology. 222(2) |
| ISSN: | 1090-2430 |
| Popis: | Dorsal root injuries (DRIs), resulting in the permanent disconnection of nerve roots from the spinal cord, lead to sensory impairments, including both the loss of sensation and the development of neuropathic pain in the affected limb. DRI results in axonal sprouting of intraspinal serotonergic fibers, but the functional consequences of this response to spinal deafferentation remains unclear. Here we aimed to clarify the role of descending serotonergic projections in both mechanosensation and pain following DRI. By ablating serotonergic input to the spinal cord via 5,7-dihydroxytryptamine (5,7-DHT) prior to DRI in rats, we found that serotonergic input to the dorsal horn normally inhibits the recovery of mechanosensation but has no effect on the development or resolution of cold pain. Endogenous brain-derived neurotrophic factor (BDNF) is upregulated by activated microglia, is required for sprouting of serotonergic axons and neuropeptide tyrosine (NPY)-positive interneurons, and suppresses mechanosensory recovery following DRI. Intriguingly, we found that the density of activated microglia, the amount of BDNF protein, and density of NPY-positive processes were all significantly reduced in 5,7-DHT-treated rats, suggesting that serotonergic input to the deafferented dorsal horn is required for all of these consequences of spinal deafferentation. These results indicate that BDNF-dependent serotonergic and/or increases in NPY-positive fiber density slows, and ultimately halts, mechanosensory recovery following DRI. |
| Databáze: | OpenAIRE |
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