Electrophysiological and Behavioral Evaluation of C-LTMR Plasticity Induced by Spinal Cord Injury: Transformation from Pleasure to Pain Afferents
Abstract
The experience of pain is reported in as many as 70% of spinal cord injury (SCI) patients. The prevalence of neuropathic pain, which is pain resulting from direct injury to the peripheral or central nervous system (including spinal cord), has not resulted in a clear understanding of the underlying mechanisms. The processes that are believed to contribute to abnormal pain processing after SCI range from changes in sensory input to inadequate brain-mediated control. For example, nerve fibers that carry pain information and nerve cells within the spinal cord that receives the pain information undergo major physical and chemical modifications that lead to alterations in their functional properties. Injury can also impair the brain s ability to exert control over the sensory signals adjacent and below the spinal cord injury level. Even above injury site sensations may be altered. One particular pain sensation is termed allodynia and is defined a painful experience to a non-painful sensory stimulus like touch. Allodynia is a common indicator of neuropathic pain in both clinical and experimental studies. This proposal will focus on whether SCI leads to changes in pleasant touch-encoding sensory nerves found in hairy skin. These afferents are known as C-low threshold mechanoreceptors (C-LTMRS). We hypothesize that activation of C-LTMRs produce mechanical (touch) allodynia after SCI. Our studies will examine whether gentle brush stimulation to the skin causes pain in adult mice. In transgenic mice, we will use light stimulation to selectively activate the C-LTMRs to further confirm whether their activation is sufficient and necessary for the painful experience caused by brush. A third study will examine if the activation of CLTMRs activates pain processing regions within the spinal cord. Pain tests will be accompanied with simultaneous measurements of respiratory and heart rates to test if sympathetic activity is linked to abnormal pain processing after SCI. The anticipated results of this proposal will identify a novel mechanism of at-level mechanism after SCI. They will also provide insight into the possible interactions between sensory processing and sympathetic signaling. These results will be applicable to the healthcare needs of many SCI patients who experience chronic pain. The current lack of adequate control for pain after SCI makes the potential outcome of this study clinically relevant. A better understanding of the processes that produce pain after SCI should be informative to the development of effective treatments. It is unclear how soon the results from this study can be translated into clinical applications. However, they will significantly contribute to the field as they are the first to examine the transformation of pleasurable touch sensations to pain and the interactions between autonomic dysfunctions and chronic pain after SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510676
Entities
People
- Sandra M Garraway
Organizations
- Emory University
- United States Army