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Last updated: Thu, Jun 22, 2017
The nervous system specializes in maintaining stability in systems by sensing the physiological state of tissue and then, when conditions are altered, producing actions that re-set the state to a required level. The duty of sensory cells is to receive incoming information. When cut off from the source of their information, the cells react by increasing their excitability to such an extent that they begin to fire both spontaneously and to distant, inappropriate inputs.1
Neuropathy is disease of the nerves: neuropathic pain is pain that results from neuropathy. Neuropathy has a very broad range of causes. Infections can damage or kill nerves, as in lupus/herpes zoster/shingles. Neuropathies can develop from other pathologies, as in diabetic neuropathy or neuropathies caused by poor circulation. Degenerative changes can cause nerves to be overly sensitive or to fire spontaneously.
The pathologies resulting from these causes are generally classified as neuralgias. Neuralgias result in fearful, usually burning pain that may occur with little or no external stimulation and that is difficult or impossible to control.
Physical injury to nerves also can lead to pathological functioning of the nervous system. This may seem counterintuitive, inasmuch as physicians have repeatedly tried to relieve stubborn pains by cutting, burning, or poisoning nerve fibers. This has been tried almost everywhere in the body where nervous paths can be accessed, from the periphery to the spinal cord to various locations in the brain. The theory behind such interventions is that, since "pain signals" travel through these paths, interrupting the paths will interrupt the pain signals, thereby stopping the pain.
In some cases the interruption of signals causes an initial reduction in or even relief of symptoms. The symptoms return however, often starting as a tingling then building up to full-blown pain that is sometimes worse than the original pain. The explanation of these phenomena provides insight into how your nervous system works.
When a peripheral (sensory) nerve is cut, the immediate result is a large volley of signals to the spine. This sensitizes the spinal neurons, as we've seen in the case of a normal injury. At this point, the cut sensory nerve falls silent. The cut fiber doesn't normally die, however, since the cell body in the dorsal root ganglion survives. The cut fiber begins to attempt to repair itself.
In the meantime, the spinal neurons that would normally be stimulated by the cut neurons receive no stimulation from them. This causes them to increase their sensitivity. This is part of their normal behavior. They “expect” to receive signals and, when they don't, they respond by turning up their sensitivity.
Long-term changes continue in the spine. Sensitization of spinal neurons leads to changes in their receptive fields. This allows both adjacent sensory neurons and normally innocuous sensors to stimulate nociceptive interneurons, which triggers sensations of pain. In some cases, spinal neurons spontaneously discharge in a manner similar to epilepsy, resulting in pain with no peripheral stimulation.
Cut sensory fibers soon seal themselves off by closing the cell membrane over the cut axon. They begin to grow new sub-fibers. These new fibers will tend to follow the path of the cut nerve if the cells that encase the nerve are still alive and intact. However, they tend to form dense tangled masses of sensory endings called neuromas. These neuromas are sensitive and, if they are near the skin surface or any other place where they are liable to stimulation, they will fire action potentials up the sensory axon. When these signals arrive at the spine, they encounter spinal neurons that are hyperexcitable, and the result is pain disproportionate to the stimulation.
The new nerve endings will often find themselves in a different type of tissue from the original nerve endings. This is eventually communicated through the axon to the spinal neurons. It is interpreted as a signal that there is tissue damage at the nerve endings, which causes the reaction of the spinal neurons to become more intense.
Peripheral nerve injury or severe or extended peripheral inflammation provoke a similar set of reactions in the spinal cord. Stimulation of C fibers causes microglia to proliferate in the spine. Microglia and astrocytes both respond to various neurotransmitters and are able to secrete pro-inflammatory, pro-pain substances within the spine. Astrocytes are connected to each other by membrane receptors called connexins that are essentially open pores that connect groups of astrocytes. The connexins allow small pro-pain signaling molecules to diffuse through the astrocytes and out into the intercellular fluid within the spine, potentially spreading sensitization to spinal neurons associated with anatomically distant parts of the body.