Group C nerve fiber

Location C fibers are one class of nerve fiber found in the nerves of the somatic sensory system. They are afferent fibers, conveying input signals from the periphery to the central nervous system. Structure C fibers are unmyelinated unlike most other fibers in the nervous system. These occur when a non-myelinating Schwann cell bundles the axons close together by surrounding them. The Schwann cell keeps them from touching each other by squeezing its cytoplasm between the axons. The condition of Remak bundles varies with age. The number of C fiber axons in each Remak bundle varies with location. For example, in a rat model, large bundles of greater than 20 axons are found exiting the L5 dorsal root ganglion, while smaller bundles of average 3 axons are found in distal nerve segments. Multiple neurons contribute axons to the Remak bundle with an average ratio of about 2 axons contributed per bundle. The cross sectional area of a Remak bundle is proportional to the number of axons found inside it. Remak bundles in the distal peripheral nerve are clustered with other Remak bundles. The Remak Schwann cells have been shown to be electrochemically responsive to action potentials of the axons contained within them. In experiments where nerve injury is caused but nearby C fibers remain intact, increased spontaneous activity in the C fibers is observed. This phenomenon supports the theory that damaged nerve fibers may release factors that alter the function of neighboring undamaged fibers. Study of Remak bundles has important implications in nerve regeneration after sustaining injury. Currently, recovery of distal C fiber function takes months and may still only regain incomplete function. This may result in abnormal sensory function or neuropathic pain. Remak bundles are thought to release certain trophic factors that promote the regeneration of the damaged axons. ==Pathway==

C fibers synapse to second-order projection neurons in the spinal cord at the upper laminae of the dorsal horn in the substantia gelatinosa. The second-order projection neurons are of the wide dynamic range (WDR) type, which receive input from both nociceptive terminals as well as myelinated A-type fibers. These classifications are based on their responses to mechanical stimuli. The second-order neurons ascend to the brain stem and thalamus in the ventrolateral, or anterolateral, quadrant of the contralateral half of the spinal cord, forming the spinothalamic tract. The spinothalamic tract is the main pathway associated with pain and temperature perception, which immediately crosses the spinal cord laterally. This crossover feature is clinically important because it allows for identification of the location of injury. ==Function==

Because of their higher conduction velocity owing to strong myelination and different activation conditions, Aδ fibers are broadly responsible for the sensation of a quick shallow pain that is specific on one area, termed as first pain. C fibers are considered polymodal because they can react to various stimuli. They react to stimuli that are thermal, or mechanical, or chemical in nature. For example, they can respond to hypoxia, hypoglycemia, hypo-osmolarity, the presence of muscle metabolic products, and even light or sensitive touch. • C mechano- and metabo- receptors in muscles or joints • responsible for muscle exercise, burn and cramp Capsaicin activates C fibers by opening a ligand-gated ion channel and causing an action potential to occur. VR1 is essential for the inflammatory sensitization to noxious thermal stimuli. ==Role in neuropathic pain==

Activation of nociceptors is not necessary to cause the sensation of pain. There are four main classes: • peripheral focal and multifocal nerve lesions • traumatic, ischemic or inflammatory • peripheral generalized polyneuropathies • toxic, metabolic, hereditary or inflammatory • CNS lesions • stroke, multiple sclerosis, spinal cord injury • complex neuropathic disorders • complex regional pain syndromes [CRPSs] Irregular grouping of these channels in sites of the abnormal activity may be responsible for lowering the activation threshold, thus leading to hyperactivity. This event is called 'windup' and relies on a frequency greater or equal to 0.33 Hz of the stimulus. Windup is associated with chronic pain and central sensitization. This minimum frequency was determined experimentally by comparing healthy patient fMRI's when subjected to varying frequencies of heat pulses. The fMRI maps show common areas activated by the TSSP responses which include contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP events are also associated with other regions of the brain that process functions such as somatosensory processing, pain perception and modulation, cognition, pre-motor activity in the cortex. Treatment Currently, the availability of drugs proven to treat neuropathic pain is limited and varies widely from patient to patient. Many developed drugs have either been discovered by accident or by observation. Some past treatments include opiates like poppy extract, non-steroidal anti-inflammatory drugs like salicylic acid, and local anesthetics like cocaine. Other recent treatments consist of antidepressants and anticonvulsants, although no substantial research on the actual mechanism of these treatments has been performed. However, patients respond to these treatments differently, possibly because of gender differences or genetic backgrounds. Therefore, researchers have come to realize that no one drug or one class of drugs will reduce all pain. Research is now focusing on the underlying mechanisms involved in pain perception and how it can go wrong in order to develop an appropriate drug for patients afflicted with neuropathic pain. ==Microneurography==

Microneurography is a technique using metal electrodes to observe neural traffic of both myelinated and unmyelinated axons in efferent and afferent neurons of the skin and muscle. This technique is particularly important in research involving C fibers. A supplemental method used to better understand these readings involves examining recordings of post-spike excitability and shifts in latency; these features are associated with changes in membrane potential of unmyelinated axons like C fibers. Moalem-Taylor et al. experimentally used chemical modulators with known effects on membrane potential to study the post-spike super-excitability of C fibers. The researchers found three resulting events. Chemical modulators can produce a combination of loss of super-excitability along with increased axonal excitability, indicating membrane depolarization. Secondly, membrane hyperpolarization can result from a blockade of axonal hyperpolarization-activated current. Lastly, a non-specific increase in surface charge and a change in the voltage-dependent activation of sodium channels results from the application of calcium. == Philosophical relevance ==

C fibers have repeatedly appeared in philosophical discussions on theory of mind: István Aranyosi refers to their usage as "philosophers' favourite piece of folk neuroscience". While most responses in the field have challenged this identity on philosophical grounds, others have objected by calling it scientifically unjustified. ==See also==