Question

There are a number of disorders that result in people experiencing chronic (long-term) pain even though there might be no known physical cause for this pain. This can result from the transmission of action potentials even though under normal circumstances, the size of the stimulus might not warrant an AP transmission, or at least not as frequent a transmission.

What could be a possible cause for this phenomenon? [It can not be a change in the brain itself, or a problem with the interpretation of the signal in the brain. Nor can neurons change their threshold potential. In other words, what could change in or near a neuron to cause more frequent AP transmissions?]

Answer 1

An action potential, initiated in an afferent axon, arrives at a bouton and hypopolarizes it. Boutons hypopolarize in the same way as axons. At this point the action potential itself can go no farther, but the hypopolarization of the bouton somehow causes some of the synaptic vesicles in the region to fuse with the presynaptic membrane whereupon the fused membrane breaks and spills the contents of the vesicles into the synaptic cleft. The release of transmitter substances depends upon several factors, including the magnitude of the hypopolarization, the number of available vesicles, and, importantly, the concentration of calcium in the extracellular fluid. Reduced calcium blocks synaptic transmission. Likewise, increased manganese, a calcium inhibitor, leads to depression or block of transmission. Calcium appears to be necessary for hypopolarization-release coupling. Hypopolarization leads to opening of voltage-gated Ca++ channels and the entry of Ca++ into the terminal. Once inside, Ca++ promotes fusion of the vesicles with the terminal membrane and release of the transmitter substance. The released transmitter substance diffuses across the cleft in a fraction of a millisecond and interacts with the postsynaptic membrane, changing its permeability and, ultimately, the membrane potential at that point on the postsynaptic membrane. The action of the transmitter substance is terminated by its removal from receptors on the postsynaptic membrane. Some transmitter substances are then degraded, e.g., acetylcholine, whereas others are taken up by the presynaptic terminal, e.g., norepinephrine and other amine transmitter substances. This entire process, from presynaptic spike to the termination of the postsynaptic response, frequently requires only 10-20 msec.