[5] 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.

[6] 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.

[1] The spinothalamic tract is the main pathway associated with pain and temperature perception, which immediately crosses the spinal cord laterally.

[1] C fibers respond to stimuli which have stronger intensities and are the ones to account for the slow, lasting and spread out second pain.

[8] For example, they can respond to hypoxia, hypoglycemia, hypo-osmolarity, the presence of muscle metabolic products, and even light or sensitive touch.

[8] C fiber receptors include: This variation of input signals calls for a variety of cells of the cortex in lamina 1 to have different modality-selectiveness and morphologies.

[10] Capsaicin activates C fibers by opening a ligand-gated ion channel and causing an action potential to occur.

[5] This alteration of normal activity is explained by molecular and cellular changes of the primary afferent nociceptors in response to the nerve damage.

[14] After nerve damage or repeated stimulation, WDR (wide dynamic range) neurons experience a general increase in excitability.

Nitric oxide is thought to migrate back to the presynaptic membrane to enhance the expression of the voltage-gated N-calcium channels resulting in a pain wind-up phenomenon.

[5] Central sensitization of the dorsal horn neurons that is evoked from C fiber activity is responsible for temporal summation of "second pain" (TSSP).

[15] 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).

[12] Some past treatments include opiates like poppy extract, non-steroidal anti-inflammatory drugs like salicylic acid, and local anesthetics like cocaine.

[12] 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.

[16] Recordings from efferent postganglionic sympathetic C fibers of the muscles and skin yield insights into the neural control of autonomic effector organs like blood vessels and sweat glands.

[16] Readings of afferent discharges from C nociceptors identified by marking method have also proved helpful in revealing the mechanisms underlying sensations such as itch.

[17] Moalem-Taylor et al. experimentally used chemical modulators with known effects on membrane potential to study the post-spike super-excitability of C fibers.

[17] Chemical modulators can produce a combination of loss of super-excitability along with increased axonal excitability, indicating membrane depolarization.

Some 20th century arguments for materialism have customarily identified pain as a physical event in the nervous system, such as "C fibers firing.

"[19][20] While most responses in the field have challenged[21] this identity on philosophical grounds, others have objected[22] by calling it scientifically unjustified.