1/2. role of kinins in pain and hyperalgesia: psychophysical studies in a patient with kininogen deficiency.1. bradykinin is considered to be an important mediator of pain and hyperalgesia associated with injury and inflammation. Psychophysical studies were conducted in a patient with complete kininogen deficiency to determine whether the absence of bradykinin was associated with abnormalities in pain sensibility. Pain evoked by heat stimuli to the thenar eminence was tested before and after a localized burn, which has been shown to cause hyperalgesia in normal subjects. In addition, pain evoked by intradermal administration of bradykinin (0.1-10 micrograms) to the forearm and the effects of bradykinin on pain induced by heat stimuli were studied. The patient rated the intensity of pain evoked by all heat stimuli relative to the pain induced by a 3 s 45 degrees C stimulus. 2. The patient's heat pain threshold (45 degrees C) in the glabrous skin was similar to that of age-matched control subjects (n = 5) and to that previously observed in younger control subjects. 3. The burn resulted in a decrease in pain threshold and an increase in pain induced by suprathreshold stimuli. The magnitude of hyperalgesia was within the range observed in the age-matched control subjects and in younger control subjects. Thus, kinins are not essential for the development of hyperalgesia after heat injury. 4. In control subjects, intradermal injections of bradykinin produced pain and hyperalgesia to heat stimuli. In the patient, intradermal bradykinin injections induced minimal pain and no hyperalgesia to heat stimuli. Thus, congenital absence of kininogens may be associated with a deficiency in bradykinin receptors.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/2. Chronic hyperalgesia and skin warming caused by sensitized C nociceptors.A patient suffering from an acquired painful syndrome, due to injury to primary somatic afferent units, was studied. Clinical features included chronic spontaneous burning pain in one hand, abnormal painful response to nonnoxious cutaneous stimuli, and deviation of temperature and dystrophic changes in symptomatic skin. Diagnostic stellate ganglion blocks did not improve spontaneous or stimulus-induced pains, and observation of sympathetic efferent neural activity and vasomotor effector responses revealed no abnormality, failing to support an autonomic contribution to the pathogenesis of the pains. A quantitative psychophysical assessment documented exaggerated magnitude of pain in response to noxious stimuli in symptomatic skin, together with abnormal painful quality and prolongation of sensation induced by nonnoxious tactile or warm stimuli. Such mechanical and thermal hyperalgesia persisted during A fibre blocks, suggesting transmission by primary afferents with unmyelinated C fibres and implying sensitization of C polymodal nociceptors. Direct microneurographic recordings of single, identified C polymodal nociceptors from symptomatic skin confirmed the presence of units with pathologically enhanced receptor responses: lowered threshold and very prolonged afterdischarges. While bypassing skin receptors, strongly intraneural microstimulation in fascicles supplying symptomatic or control skin evoked equivalent magnitudes and temporal profiles of pain from both sides. Thus secondary CNS dysfunction need not be postulated to explain the painful syndrome. skin grafted onto the affected region partially recovered tactile and thermal sensation (but not pain) without expressing the painful syndrome. This supports the overall conclusion that in this patient A fibres are not involved as primary carriers of input decoded as pain. Sensitization of C polymodal nociceptors is consistent with the features of hyperalgesia in this patient: pain evoked by nonnoxious stimuli, exaggerated pain magnitude, and abnormally prolonged aftersensation of pain. This is the first documentation of chronic sensitization of human C polymodal nociceptors as a symptom of disease. In the context of sensitized C nociceptors and in the absence of sympathetic vasoconstrictor deficit, the abnormally elevated temperature in symptomatic skin is interpreted as due to antidromic vasodilatation triggered by neurosecretion from hyperactive nociceptors.(ABSTRACT TRUNCATED AT 400 WORDS)- - - - - - - - - - ranking = 0.2keywords = physical (Clic here for more details about this article) |