Information about the impulse is coded by impulse frequency, a form that is accessible to the brain for decoding and interpreting the message as a painful experience. Subtypes of PANS are located in the skin, subcutaneous tissue, muscles, and joints. These subtypes are defined by their microscopic appearance, conduction velocity, and pattern of responses Verteporfin
to chemical, thermal, and mechanical stimuli. Visceral PANS are found in the gastrointestinal tract, cardiopulmonary system, and genitourinary tract, and are activated by irritation, torsion, traction, or distention, particularly in conjunction with inflammation. Impulses generated by visceral nociceptors are conducted via splanchnic nerve fibers. Sequentially, the A�� and C peripheral nerve fibers transmit the electrical painful stimuli to the dorsal horn of the spinal cord via the dorsal root ganglion. The A�� fibers, conducting at 5�C30?m/s, are thin, myelinated fibers that elicit sharp, localized pain. In contrast, C fibers, conducting at <2?m/s, are unmyelinated and elicit <a href="http://www.selleckchem.com/products/VX-770.html
">www.selleckchem.com/products/VX-770.html dull, diffuse pain. Transmission of painful stimuli along these nerve fibers is facilitated by glutamate which is an efficient excitatory neurotransmitter throughout the nervous system. Contrariwise, gamma-aminobutyrate (GABA) is an inhibitor of the transmission of electrical stimuli [25, 26, 28, 29]. Excitation by glutamate or inhibition by GABA is achieved either by decreasing the negativity CH5424802 order
(depolarization) or by increasing the negativity (hyperpolarization), respectively, of the action potential across membranes of nerve cells and nerves. At the level of the dorsal root ganglion, connections with the autonomic nervous system occur which may explain some of the signs and symptoms of pain such as the changes in blood pressure and heart rate. At the level of the dorsal horn of the spinal cord, the pain stimulus crosses over to the contralateral side and ascends along the spinothalamic tract to make connections with the brainstem, hypothalamus, thalamus, limbic system (mediator of emotion and memory), reward system (mediator of pleasure and addiction), glia, and the prefrontal cortex where pain sensation is perceived. The most important aspect of the intermittent of VOC is the lack of pain between successive episodes irrespective of frequency. Its incidence, however, varies from one to several per year, and it is more common in children. What makes the VOC intermittent or intractable depends on the severity of the painful impulse and more importantly on how the painful signal is processed in the neurons of the dorsal horn of the spinal cord which is the gateway to the central nervous system. The traffic at this juncture may accentuate or attenuate the intensity of the painful stimulus.