These pathways include sensory fibers that carry pain information from the body to the spinal cord, as well as cells that relay this information to the brain. Nerve pathways in the spinal cord help process pain and other sensory information from the skin and relay it to the brain. Learning more about the causes of chronic pain is necessary to help develop more effective therapies. Pain that persists more than three months after the damaged tissue has healed is known as chronic pain, and it is a serious problem that is often difficult to treat. It alerts the body to harm but only lasts a short time and usually goes away on its own. Day-to-day pain like a stubbed toe or a pricked finger is called acute pain. eLife digestÄespite being unpleasant, pain is critical to survival because it acts as a warning for damage or impending harm. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing.
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