Pain
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Randomized Controlled Trial Clinical Trial
Spatial mapping of the zone of secondary hyperalgesia reveals a gradual decline of pain with distance but sharp borders.
The purpose of this study was to examine how pain to punctate mechanical stimuli varies with position within the zone of secondary hyperalgesia. Secondary hyperalgesia was produced by an intradermal injection of capsaicin (50 microg) into the volar forearm of human volunteers (n=9). Before and at 20, 60 and 100 min after the capsaicin injection, a computer-controlled electromechanical stimulator was used to deliver controlled-force stimuli to the skin via a 12-mm wide, 100-microm thick blade probe. ⋯ This finding unlikely reflects a ceiling effect because pain ratings within the zone of secondary hyperalgesia increased linearly with force. The relatively uniform pain ratings to the blade stimuli within the zone of secondary hyperalgesia and the sharp border that delimits the zone of hyperalgesia indicate that this sensory disturbance approaches being an 'all-or-nothing' phenomenon. Thus, a two-state model for central plasticity is needed to explain secondary hyperalgesia.
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Clinical Trial
Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks.
Although calcitonin gene-related peptide (CGRP) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks, it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood. The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls. Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included. ⋯ The findings could not be explained by confounding factors such as age, sex or use of contraceptive pills. We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack. It is hypothesized that this finding may reflect a long-lasting or permanent abnormal neurogenic vascular control in patients with migraine.
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Human subjects infected with herpes or varicella-zoster viruses complain of pain, such as allodynia, in or near the region with vesicles. However, the mechanisms of the pain are unclear. We show for the first time that infection with herpes simplex virus type-1 (HSV-1) induces allodynia and hyperalgesia in mice. ⋯ In contrast, when started from days 5 or 6, acyclovir treatment slightly inhibited the development of skin lesions and the viral proliferation, but not allodynia and hyperalgesia. These results suggest that the propagation of HSV-1 in the dorsal root ganglia produces allodynia and hyperalgesia as a result of functional abnormality of the sensory neurons in mice. This may be a useful model for studying the mechanisms of herpetic pain.
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Chronic delivery of anti-nociceptive molecules by means of cell grafts near the pain processing centers of the spinal cord is a newly developing technique for the treatment of neuropathic pain. The rat neuronal cell line, RN33B, derived from E13 rat brainstem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat brain-derived neurotrophic factor cDNA (BDNF), and the BDNF-synthesizing cell line, 33BDNF.4, was isolated. The 33BDNF.4 cells synthesized mature BDNF protein at permissive temperature (33 degrees C), when the cells were proliferating, and during differentiation at non-permissive temperature (39 degrees C) in vitro. ⋯ Transplants of the control 33V1 cells had no effect on the allodynia and hyperalgesia induced by CCI and these cells did not synthesize BDNF in vivo. These data suggest that a chronically applied, low local dose of BDNF supplied by transplanted cells near the spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of neural cell lines that are able to deliver anti-nociceptive molecules, such as BDNF, in a model of chronic pain offers a novel approach to pain management and such 'biologic minipumps' can be developed for safe use in humans.
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Neuropathic pain is often associated with the appearance of pain in regions not related to the injured nerve. One mechanism that may underlie neuropathic pain is abnormal, spontaneous afferent drive which may contribute to NMDA-mediated central sensitization by the actions of glutamate and by the non-opioid actions of spinal dynorphin. In the present study, injuries to lumbar or sacral spinal nerves elicited elevation in spinal dynorphin content which correlated temporally and spatially with signs of neuropathic pain. ⋯ Spinal injection of antiserum to dynorphin A((1-17)) and of MK-801 both blocked thermal hyperalgesia, but not tactile allodynia, of the hindpaw after S(2) ligation. These data suggest that the elevated spinal dynorphin content consequent to peripheral nerve injury may drive sensitization of the spinal cord, in part through dynorphin acting directly or indirectly on the NMDA receptor complex. Furthermore, extrasegmental increases in spinal dynorphin content may partly underlie the development of extraterritorial neuropathic pain.