MORE than 4 million Americans suffer from neuropathic pain after nerve injury. The pain is often so intense that individuals cannot work or continue their normal lives. For some individuals, they are so desperate to escape the pain they seek to end their own lives. Available painkillers are ineffective or only partially effective for treatment. The underpinnings of neuropathic pain are not fully understood, and there is, yet, no cure.
It is common after spinal cord injury for the pain-alert system to malfunction. Instead of pain sounding off during an actual emergency, the nervous system produces a painful feeling without any bodily harm. A fan blowing air across your arm might feel like a cool breeze. From your memory, this is what you anticipate, but as you begin to feel the cool air, the brushing across your skin immediately turns into a hot burning sensation, like a scorching iron against your arm. The damaged nervous system is converting a non-painful stimulus—the cool breeze—into a painful sensation. After nerve trauma, spontaneous pain can also occur without any reason. This heightened and spontaneous pain state is called “neuropathic pain”.
An interesting line of study is based upon the idea that neuropathic pain is due to faulty ‘re-wiring’ of pain circuitry after nerve injury (i.e., SCI). A mechanism, first studied in memory processing, may help scientists understand how to reduce neuropathic pain after nervous system injury.
Pain and memory use neural circuits made of a network of many neurons. A neuron is a cell whose purpose is to transmit electrical signals, which control different tasks, such as muscle movement and transmission of sensory information about the environment. A typical neuron has a cell body with branches and cables giving it the appearance of a simple tree. Dendrites are the complex branches and act as antennae for receiving signals. The axon is the shaft, or trunk, that transmits information to other cells.
A key feature of many neurons is dendritic spines (see picture above), which are microscopic “mushroom” and “thin-finger” shaped extensions on the receiving branches of the neuron tree. Dendritic spines are like protruding electrical sockets for an axon from another neuron to plug into, and act as contact points for cell-to-cell communication. Like thorns on a rose stem, dendritic spines spread across the surface of a neuron’s numerous branches. A single neuron may contain hundreds to thousands of dendritic spines.
Memory studies in the brain have revealed most of what we know about dendritic spines. Prior to learning, the majority of dendritic spines change shape rapidly, appear or disappear over seconds and minutes, also known as “twitching”. As a memory forms, dendritic spines slow their twitching, and many mature into stabilized mushroom-shaped structures.
Nerve injury causes similar dendritic spine changes. Results show that after injury to leg nerves in animal models, neurons that transmit pain in the spinal cord have more dendritic spines and more spines have mushroom shapes, showing that they are stable, mature spines. Computer simulations show that increased spine number and mature spines are an important factor toward changing the electrical activity patterns associated with neuropathic pain.
To test the hypothesis, investigators used a drug designed to disrupt spine structure to see if that would reduce neuropathic pain.
Researchers brushed, pinched, and poked the skin of adult rats 10 days after nerve injury to confirm that they had produced neuropathic pain. Neurons in the spinal cord pain-pathway responded with excessive electrical activity, or were hyperactive, towards these stimulations. This electrical hyperactivity is associated with neuropathic pain.
Drug treatment that disrupted dendritic spines reduced excessive electrical activity and improved behavioral neuropathic pain symptoms in nerve injured animals. Using a 3D-visualization technique, investigators also found that dendritic spine shape and number returned closer to normal. These results suggest that nerve injury causes dendritic spine changes in the pain-pathway circuitry and contributes to neuropathic pain states.
Overall, it seems that memory research and neuropathic pain studies converge: dendritic spines are important in both chronic pain and memory. This means that the large body of research that exists for understanding memory can potentially be applied toward studying neuropathic pain and developing a cure.
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