It is necessary to recognize that in spite of the existence of laboratories of high technology and the appearance of surgical innovations, the pain is still at the present time one of the most amazing mysteries which the whole humanity faces.
Chemical modulation of pain transmission occurs via several neurotransmitter-receptor systems that have been shown to affect the spinal processing of nociceptive input. Excitatory neurotransmitters (e.g., substance P), are active in spinal cord and enhance pain transmission. The inhibitory elements are the opioids, the α2-adrenergic fibers, γ- aminobutyric acid, and the serotoninergic and adenosinergic receptors. Endogenous neurotransmitters, like exogenously administered analgesics, work on dorsal horn neurons to inhibit excitatory transmitter release and consequently to decrease pain and perception.
Pain can be the result of the stimulation of the receptors of the pain (nociceptors), which are located in three main body areas: skin, musculoskeletal and visceral structures. Nociception is the neural answer to the application of injurious stimuli. Nociceptive reflex can happen without the perception of the painful stimulate that initiates the reflex.
The perception of the pain is indicated through voluntary actions. Chemical mediators are important components of the nociceptive reflex and offer a target of pharmacologic modulation. Pain mediators included: adrenocorticotropic hormone (ACTH), glucocorticoids, vasopressin, oxitocin, catecholamines, brain opiods, angiotensin II, endorphin / encephalin, vasoactive intestinal peptide (VIP), substance P, eicosanoids (e.g., prostaglandins, leukotrienes), tissue kininogens (bradykinin), histamine, serotonin, potassium and proteolytic enzymes.
Bradykinin causes vasodilatation and increase in the vascular permeability, besides to produce hypotension. Additionally, the bradykinin produces pain and causes marginalization of the leukocytes in the blood vessels.
Pro-inflammatory effects of substance P include: plasmatic vasodilatation and extravasations; mast cell degranulation, with the consequent histamine release; (iii) leucocytes chemoattractant and proliferation; cytokines release; (v) reactive oxygen intermediates (ROI) production and granular release through polymorphonuclear leukocytes; and increase in production and release of inflammatory mediators.
Histamine is stored in granules of the mast cells. Later to that the mast cells are activated by substances such as IgE, they release histamine, which causes immediate hypersensitivity reactions. This and other effects of histamine are mediated through their interaction with specific receptors, which is in vasodilatation of the post-capillaries venules, besides to bronchi-constriction and increase in the production and flow of bronchial mucus.
Serotonin (5-hidroxytryptamine [5-HT]) is stored in granules of the dense body of platelets. The 5-HT has vasoconstrictor activity, increases the vascular permeability and promotes fibrosis, these last when increasing synthesis of collagen by the fibroblasts. The serotonin plays a preponderant role in the descendent inhibiting pathways.
Prostaglandins (PGs), in addition to being mediators of pain, also play a substantial role in the development of pain and oedema. Prostaglandins per se don't induce inflammatory signs, but that exacerbate inflammation and pain in the sites of production of mediators of pain, this through activation of specific receptors in the blood vessels and sensitive nerves.
Endogenous opioids (opium-peptins) provides with analgesia when they are released to high concentrations in certain encephalic regions. These include encephalin, dynorphin and endorphin.
The inflammatory process implies release of numerous of these chemical mediators, from injured tissues or originating of the own inflammatory cells. The control of the pain caused by these mediators is frequently widely employee on the control of the inflammatory process.
Factors such as emotional state, expectation, attention, blood pressure, stress and drugs can modulate pain, this possibly through the activation of analgesia systems, as the one of opiods. Pain can be alleviated, or its reduced intensity, through the manipulation of environment or behaviour, in addition to the drug administration. Before the pain is handled with drugs, this it will have initially to be identified and to be classified. All the pain does not require or will respond to drugs.
1. Anthony C: Acute pain in the intensive care unit. In: Shoemaker WC, Ayers SM, Genvic A et al (eds). Textbook of Critical Care. 3rd (eds). pp. 1486-1498. Philadelphia. WB Saunders. 1995.
2. Bonica JJ: Biochemistry and modulation of nociception and pain. In: Management of Pain. Lea and Febiger (eds). Second Edition. 1990. pp 96-99.
3. Lamont L, Tranquilli WJ & Grimm KG: Physiology of pain. Vet Clin North Am: Small Anim Pract. 2000: 30: 703-728.