Pain is a variable subjective reception and it involves a very complex interaction.
Something, for example a book, falls and hit your toes there will be a chain of things going to happen. First of all, the hitting creates a signal received by the sensory receptors in the proper part of the body (called nociceptors at the free nerve ending). In addition to noxious stimuli, nociceptor can become sensitive to variety of chemical factors present after a local injury. These two types of stimuli at the site will interact to produce a series of signals received by the nerve named impulse. Neural impulses are carried along the peripheral nerves, nerve root, spinal cord, brainstem, thalamus and the cortex that ultimately leads to an awareness of Pain.
Thus, when the book hits your toe, your brain receives the impulses and recognizes them as pain sensation, then you shout out AWE! Almost on the same time, when the impulse arrived the spinal cord, it exchange the information with the motor nerve (called reflex) and send a command through the motor nerve to the foot, then your foot immediately withdrew from the book. The later action is a protective action, is done by reflex, and does not need your brain to give order to do so. The former reaction might not be shouting, but biting your teeth, gripping your fists, or waving your forearms. All these are depending on the stimulated size or site, the duration of the stimuli and even the experience of your tolerance.
Activation of the receptor is the conversion of one form of energy, thermal, mechanical or chemical, into nerve impulse that is accessible to the brain. In physiology this called Transduction. Transduction occurs in the nociceptors (free nerve ending). Nociceptors can be divided into A-fiber and C-fiber. A-fiber is large and sheathed (myelinated), on the contrary, C- fiber is small and non-sheathed (not myelinated) A-fibers response to mechanical stimuli and some to thermal stimuli, and C-fiber respond to any noxious stimuli. A-fibers are responsible for early, sharp, brief pain (type I), and C-fibers are responsible to dull, prolonged pain (type II).
During injury, chemical substances are produced in the damaged area such as Serotonin, Bradykinin, Histamine and Prostglandins. These substances stimulate the nociceptors give the sensation of pain and they also are the cause of local edema or inflammation.
Neural impulses are carried along the peripheral nerves nerve roots, spinal cord, brainstem, and thalamus to the cortex. We aware the pain in the cortex level. This sequence called impulse Transmission. Majority of afferents (entering into the cord) project to the spinal cord through dorsal root (back side), but some may project to the cord through ventral root (abdominal side). A- and C- fibers segregate and enter the spinal cord. From this we can see there is a rather complicated nerve network formed in the spinal level. There is something more, in the cord there are three types of neurons (nerve intersection) named projection neurons, excitatory neurons and inhibitory interneurons. Projector neurons mainly rely to the higher center, excitatory neurons relay to motor neuron that mediate spinal reflexes, and inhibitory neurons contribute to the control of nociceptive transmission. There is a theory suggests there is interaction between myelinated and non-myelinated neurons. The myelinated afferents excite inhibitory interneurons and inhibit pain. The non-myelinated nociceptors inhibit the inhibitory interneurons. The perceived intensity is the net effect. At this point we realize the protective mechanism our body to the pain, in physiology it called Gate control. There are several chemical substances in the cord which relate to the impulse transmission included substance P, somatostatin, vasoactive intestinal polypeptide, glutamate, aspartate and adenosine triphosphate.
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In the brainstem, stimulation of some regions (periaquenductal grey and immediately adjacent to the midbrain, periventricular grey of hypothalamus, the lateral and dorsolateral pontine tegmentum and rostro ventral medulla) can reduce pains and inhibit nociceptive neurones. We found that the resulting of pain control is due to opiod peptides production from these sites. Opiod peptides are endogenous opium-like substances which provide analgesia. They are Enkephalin, B-endorphrin and Dynorphin, commonly called Endophines. This system doesn’t work when there is no pain.
In short, pain involves a complex interaction. Modification of pain occurs at the neuron network in the spinal cord. Transmit to higher levels to the thalamic, limbic system and frontal lobe of the brain, and secretion of endophines occurred. The sense of pain is the net result of all these.