Neurophysiology and Role of Inflammation in Pain

Nociceptive stimulates are transpired by the duration of the stimulus and the intensity of its application. This duration/ intensity combination is resolute in dividing physiological pain from pathological pain . In pathological pain, the duration and/or intensity of the tissue attack are unnatural. Apart from the instantaneous clinical result of such stimulation, the occurrence of sensitization happens: sustains and amplifies threshold of the nociceptors involvement, and derivation of the signal in the spinal cord is facilitated (central sensitization), which excitability threshold of the nociceptors is pronouncedly decreased (peripheral sensitization). This circle is instated very quickly, from a few minutes to a few hours after the start of tissue injury. It amplifies and sustains the pain. Nociceptors have a high activation threshold: they are just activated by stimuli of high intensity. The chemical agents participated in the activation of nociceptors include algogenic agents (those which invite pain) such as K+ and H+ ions and inflammatory mediators such as serotonin, substance P, histamine, prostaglandins (PGs).These substances are emancipated during inflammation of all sources (tumor, trauma) and have a synergistic effect: they produce lower the nociceptors activation threshold and sustained activation of them. PGs are released when tissue is injured. Their demonstrationis highly stimulated at the focus of the inflammation. prostaglandinE2 (PGE2) sensitizes the nociceptive afferents to other mediators such as bradykinin and histamine, which are potent activators of polymodal nociceptors. Serotonin increases the happening through its 5-HT3 receptors. Over time this occurrence is amplified further, as repeated stimulation invites the response to expand incrementally. Glutamate is one of the main mediators, through the alpha- amino-3- hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. The AMPA receptors seem to be involved in the transmission of stimulations of short duration. Activation of NMDAreceptors requires excitation of greater duration and/or intensity.