CaMKII Controls Whether Touch Is Painful
| Autor: | Daniel Vilceanu, Bin Pan, Gregory Fischer, Andy D. Weyer, Hongwei Yu, Cheryl L. Stucky, Andy Hudmon, Jingwei Meng, Frank L. Rice, Hsiang En Wu, Quinn H. Hogan, Alan R. Light |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pain Threshold Green Fluorescent Proteins Pain Nerve Tissue Proteins Sensory system Stimulation Motor Activity Rats Sprague-Dawley Mice Ganglia Spinal Ca2+/calmodulin-dependent protein kinase Animals Medicine Sensory deprivation Enzyme Inhibitors Skin Mechanosensation business.industry General Neuroscience Excitatory Postsynaptic Potentials Nociceptors Peripheral Nervous System Diseases Articles Dependovirus Sensory neuron Rats Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Nociception nervous system Hyperalgesia Touch Nociceptor Sensory Deprivation Calcium-Calmodulin-Dependent Protein Kinase Type 2 business Mechanoreceptors Neuroscience Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 35:14086-14102 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1969-15.2015 |
| Popis: | The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (Aβ-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of Aβ-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in Aβ-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic Aβ-LTMRs removes dorsal horn inhibition that otherwise prevents Aβ-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in Aβ-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. We conclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions.SIGNIFICANCE STATEMENTThe sensation of touch is served by specialized sensory neurons termed low-threshold mechanoreceptors (LTMRs). We examined the role of CaMKII in regulating the function of these neurons. Loss of CaMKII function, such as occurred in rats during sensory deprivation, elevated the generation and propagation of impulses by LTMRs, and altered the spinal cord circuitry in such a way that low-threshold mechanical stimuli produced pain behavior. Because limbs are protected from use during a painful condition, this sensitization of LTMRs may perpetuate pain and prevent functional rehabilitation. |
| Databáze: | OpenAIRE |
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