Spinal Dopaminergic Projections Control the Transition to Pathological Pain Plasticity via a D sub(1)D sub(5)-Mediated Mechanism
The mechanisms that lead to the maintenance of chronic pain states are poorly understood, but their elucidation could lead to new insights into how pain becomes chronic and how it can potentially be reversed. We investigated the role of spinal dorsal horn neurons and descending circuitry in plastici...
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| Published in: | The Journal of neuroscience Vol. 35; no. 16; pp. 6307 - 6317 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
22-04-2015
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| Online Access: | Get full text |
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| Summary: | The mechanisms that lead to the maintenance of chronic pain states are poorly understood, but their elucidation could lead to new insights into how pain becomes chronic and how it can potentially be reversed. We investigated the role of spinal dorsal horn neurons and descending circuitry in plasticity mediating a transition to pathological pain plasticity suggesting the presence of a chronic pain state using hyperalgesic priming. We found that when dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons were ablated before hyperalgesic priming, IL-6- and carrageenan-induced mechanical hypersensitivity was impaired, and subsequent prostaglandin E2 (PGE sub(2)) response was blunted. However, when these neurons were lesioned after the induction of priming, they had no effect on the PGE sub(2) response, reflecting differential mechanisms driving plasticity in a primed state. In stark contrast, animals with a spinally applied dopaminergic lesion showed intact IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE sub(2) injection failed to cause mechanical hypersensitivity. Moreover, ablating spinally projecting dopaminergic neurons after the resolution of the IL-6- or carrageenan-induced response also reversed the maintenance of priming as assessed through mechanical hypersensitivity and the mouse grimace scale. Pharmacological antagonism of spinal dopamine D sub(1)D sub(5) receptors reversed priming, whereas D sub(1)/D sub(5) agonists induced mechanical hypersensitivity exclusively in primed mice. Strikingly, engagement of D sub(1)/D sub(5) coupled with anisomycin in primed animals reversed a chronic pain state, consistent with reconsolidation-like effects in the spinal dorsal horn. These findings demonstrate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
| ISSN: | 0270-6474 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.3481-14.2015 |