Figure 3. A model illustrating hypothetical conditions necessary to prevent late hyperalgesia. The upper panels in each figure part represent a nociceptive input caused by the injury and inflammatory response to the damaged tissue. The lower panels represent three possible variants of the central hypersensitivity states generated in response to the afferent input with different block conditions: no block (1), short block (2), and prolonged block (3)(part I) Preinjury block. a = a minimal level of the nociceptive input necessary for initiation of the state of central hypersensitivity; b = a minimal level of the nociceptive input necessary to maintain the state of central hypersensitivity. The segment on the horizontal axis between A and B represents the time interval when the nociceptive input is unable to initiate the state of central hypersensitivity but yet strong enough to maintain it. If a preinjury block lasts beyond point A, hyperalgesia prevention will be permanent; the clinical significance of this effect is determined by the duration of afferent input that potentially can maintain hypersensitivity (AB segment). If a preinjury nerve block does not reach point A (short block) the peripheral afferent input will be strong enough to initiate central sensitization. (part II) Postinjury block. c = a minimal level of the nociceptive input necessary to reinitiate the state of central hypersensitivity (note that it is lower than level a in the part of Figure 3(I) that is necessary to initiate central hypersensitivity). There are two conditions for permanent prevention of late hyperalgesia when a block is administered with established central hypersensitivity. One condition (peripheral) is that the blockade should last until the intensity of a noxious input below the level that could potentially reinitiate central hypersensitivity (beyond the C point on the time axis). The other condition (central) is that the established hypersensitivity in the absence of afferent input caused by the block should disappear before block resolution. As in the case of preinjury block, clinical significance of the prevention of late hyperalgesia is determined by the duration of afferent input that potentially can maintain hypersensitivity (CD segment).

Figure 3. A model illustrating hypothetical conditions necessary to prevent late hyperalgesia. The upper panels in each figure part represent a nociceptive input caused by the injury and inflammatory response to the damaged tissue. The lower panels represent three possible variants of the central hypersensitivity states generated in response to the afferent input with different block conditions: no block (1), short block (2), and prolonged block (3)(part I) Preinjury block. a = a minimal level of the nociceptive input necessary for initiation of the state of central hypersensitivity; b = a minimal level of the nociceptive input necessary to maintain the state of central hypersensitivity. The segment on the horizontal axis between A and B represents the time interval when the nociceptive input is unable to initiate the state of central hypersensitivity but yet strong enough to maintain it. If a preinjury block lasts beyond point A, hyperalgesia prevention will be permanent; the clinical significance of this effect is determined by the duration of afferent input that potentially can maintain hypersensitivity (AB segment). If a preinjury nerve block does not reach point A (short block) the peripheral afferent input will be strong enough to initiate central sensitization. (part II) Postinjury block. c = a minimal level of the nociceptive input necessary to reinitiate the state of central hypersensitivity (note that it is lower than level a in the part of Figure 3(I) that is necessary to initiate central hypersensitivity). There are two conditions for permanent prevention of late hyperalgesia when a block is administered with established central hypersensitivity. One condition (peripheral) is that the blockade should last until the intensity of a noxious input below the level that could potentially reinitiate central hypersensitivity (beyond the C point on the time axis). The other condition (central) is that the established hypersensitivity in the absence of afferent input caused by the block should disappear before block resolution. As in the case of preinjury block, clinical significance of the prevention of late hyperalgesia is determined by the duration of afferent input that potentially can maintain hypersensitivity (CD segment).

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