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Afferent Pain Pathways: a Neuroanatomical Review

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Afferent Pain Pathways: a Neuroanatomical Review Brain Research 1000 (2004) 40–56 www.elsevier.com/locate/brainres Review Afferent pain pathways: a neuroanatomical review Tatiana F. Almeida*, Suely Roizenblatt, Sergio Tufik Department of Psychobiology, Universidade Federal de Sa˜o Paulo, Rua Napolea˜o de Barros, 925. Vila Clementino, 04024-002, Sa˜o Paulo, SP, Brazil Accepted 23 October 2003 Abstract Painful experience is a complex entity made up of sensory, affective, motivational and cognitive dimensions. The neural mechanisms involved in pain perception acts in a serial and a parallel way, discriminating and locating the original stimulus and also integrating the affective feeling, involved in a special situation, with previous memories. This review examines the concepts of nociception, acute and chronic pain, and also describes the afferent pathways involved in reception, segmental processing and encephalic projection of pain stimulus. The interaction model of the cerebral cortex areas and their functional characteristics are also discussed. D 2004 Elsevier B.V. All rights reserved. Theme: Sensory systems Topic: Pain pathways Keywords: Nociception; Afferent pain pathway; Tract; Supraspinal projection; Cortical structure 1. Introduction characterized as nociceptive pain. However, it is known that the painful phenomenon can occur spontaneously, as is the In 1986, the International Association for the Study of case for nonnociceptive pain represented by the reduction of Pain (IASP) defined pain as a sensory and emotional expe- the receptor thresholds due to alterations of the central rience associated with real or potential injuries, or described nervous system (CNS) [22]. There is a difference between in terms of such injuries. Pain has an individual connotation the terms nociception and pain; the first refers to the neuro- and suffers the influence of previous experiences [75]. This physiologic manifestations generated by noxious stimulus, definition takes into consideration the subjectivity of the while the second involves the perception of an aversive painful phenomenon and permits the understanding of im- stimulus, which requires the capacity of abstraction and the portant concepts concerning this subject. elaboration of sensory impulses [76]. Painful manifestations can be explained on the basis of According to the IASP definition, the relation between neural substrates mediating the sensory, affective, and pain and degree of injury is not obligatory. Thus, the alert nociceptive functions, as well as neurovegetative responses. function applies only to an acute manifestation, i.e., the one While the sensory, discriminative–perceptive component that follows damage to the tissue. Acute pain is character- permits the spatial and temporal localization, physical ized by the fact of being delimited in time and disappearing qualification and the intensity quantification of the noxious with the resolution of the pathological process. Chronic pain stimulus, the cognitive–affective component attributes emo- that persists for an extended period of time is associated tional coloring to the experience, being responsible for the with chronic pathological processes and causes suffering in behavioral response to pain [22]. multiple systems [75,79]. A noxious stimulus is capable of provoking a real or Knowing that pain represents a complex sensory modality potential injury, not necessarily causing pain. In this context, accompanied by affective, motivational and cognitive pain experienced by virtue of this type of stimulus is aspects, and also, associated with neurovegetative responses, this review provides neuroanatomical evidences of the neural pathways involved in the reception, processing, and trans- * Corresponding author. R. Vieira de Morais 601, ap: 116, Campo Belo, 04617-011, Sa˜o Paulo, SP, Brazil. Tel: +55-11-5539-0155; fax: +55- mission of the afferent nociceptive input because these 11-5572-5092. aspects are considered of fundamental importance for pain E-mail address: [email protected] (T.F. Almeida). perception. 0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.10.073 T.F. Almeida et al. / Brain Research 1000 (2004) 40–56 41 2. Peripheral receptors of the A-Delta afferents. Their prolonged potentials undergo summation along time and induce the manifestations of dull The propagation of pain is initiated with the activation of pain. Although widely used, this differentiation does not physiological receptors, called nociceptors, widely found in apply to all organs, being more evident in the skin [22]. the skin, mucosa, membranes, deep fascias, connective The C-type fibers present thermosensitive receptors tissues of visceral organs, ligaments and articular capsules, reacting to heating and cooling, mechanoreceptors of low periosteum, muscles, tendons, and arterial vessels. The threshold and specific receptors for algogenic substances receptors correspond to free nervous endings and represent such as potassium ions, acetylcholine, proteolytic enzymes, the more distal part of a first-order afferent neuron consist- serotonin, prostaglandin, substance P, and histamine. Many ing of small-diameter fibers, with little or unmyelinated, of C fibers with high-threshold receptors respond equally to the A-Delta or C type, respectively. Their receptor fields can thermal and mechanical stimuli, or are sensitive to mechan- consist of areas ranging from punctiform regions to regions ical, thermal and chemical stimuli, and for this reason are measuring several millimeters in diameter, or even of more called, polymodal. A special type of C fiber respond to high than one site in distant territories [69,74]. intensity thermal stimuli and, in association with polymodal The nociceptors found in the skin originate from small fibers, seem to be responsible for the mediation of the flare nervous stems that, when approaching the epidermis, lose response after tissue damage. Another type of C fiber of their myelin, ramifying into extensive plexuses. Two types slow conduction, mechanoinsensitive, and mediated by of free nervous endings exist: the ramified ones originating histamine is also recognized and is probably involved in from 1 or 2 myelinated fibers forming intraepithelial termi- the burning sensation. Finally, a new class of fibers is nations and the nonencapsulated glomerular bodies, deriv- described having receptors that do not respond to noxious ing from a single unmyelinated fiber and organized in a stimuli in general, called silent receptors, which are activat- densely spiral manner below the epidermis or the mucosa. In ed only in the presence of inflammation [76,102]. other organs, this organization may vary because the type of The A-Delta fibers are classified into two groups. The propagated stimulation, the form of propagation, and the first one, type I, corresponds to fibers with high-threshold quality of the painful sensation depend on the receptor mechanoreceptors that primarily respond to mechanical nervous fiber complex and the innerved organ [76,102]. stimuli of high intensity and respond weakly to thermal or Normally, the painful sensation results from specific chemical stimuli and, after being sensitized, to harmful heat. activation of the nociceptors by mechanical, thermal, or Group II presents fibers with mechanothermal receptors for chemical stimulus, and not by the hyperactivity of other high temperatures (45–53 jC) and some receptors for sensory modality receptors. They present higher thresholds intense cold ( À 15 jC) and later sensitized to vigorous than the other receptors and respond progressively accord- mechanical stimuli at nonnoxious thresholds [76]. ing to the intensity of the stimulus. However, the sensitiza- In the muscle, the stimulus in both A-Delta and C fibers tion of the nociceptors causes reduction of the thresholds produces an aching sensation, without differentiation, which and, in some cases, spontaneous activity [74,76,102]. is less localized than cutaneous pain. The A-Delta fibers propagate innocuous mechanical, thermal and chemical stimuli, noxious stimuli typical of ischemia/hypoxia, and 3. Peripheral afferent fibers painful pressure, being recognized as polymodal type fibers. About one-third of these fibers present special receptors that First-order afferent fibers are classified in terms of signal the amount of effort performed by a muscle group, structure, diameter, and conduction velocity. C-type fibers inducing alterations in the blood flow and in respiration are unmyelinated, ranging in diameter from 0.4 to 1.2 Am process. The C-type fibers present the same polymodal and have a velocity of 0.5–2.0 m/s; A-Delta fibers are characteristics as the A-Delta fibers, but with a 50% higher barely myelinated, ranging in diameter from 2.0 to 6.0 Am proportion of fibers for ischemia/hypoxia and noxious and have a velocity of 12–30 m/s. The A-Beta fibers are pressure [76,102]. myelinated, with a diameter of more than 10 Am and a In visceral organs, the noxious and nonnoxious informa- velocity of 30–100 m/s, and do not propagate noxious tion is propagated by A-Delta and C fibers, and not by potentials in normal situations; however, they are funda- genuine A-Beta fibers [76]. Because electric stimuli of low mental in the painful circuitry because they participate in the intensity elicit vagal sensations of fullness and nauseas, mechanisms of segmental suppression [76,95]. while electric stimuli of high intensity cause pain, it is In the presence of a noxious stimulus, the primary believed that the
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