Articles: hyperalgesia.
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Local sensitization to noxious stimuli has been previously described in acute whiplash injury and has been suggested to be a risk factor for chronic sequelae following acute whiplash injury. In this study, we prospectively examined the development of tender points and mechano-sensitivity in 157 acute whiplash injured patients, who fulfilled criteria for WAD grade 2 (n=153) or grade 3 (n=4) seen about 5 days after injury (4.8+/-2.3) and who subsequently had or had not recovered 1 year after a cervical sprain. Tender point scores and stimulus-response function for mechanical pressure were determined in injured and non-injured body regions at specific time-points after injury. ⋯ Tenderness was found in the neck region and in remote areas in non-recovered patients. The stimulus-response curves for recovered and non-recovered patients were similar after 12 days and 107 days after the injury, but non-recovered patients had steeper stimulus-response curves for the masseter (p<0.02) and trapezius muscles (p<0.04) after 384 days. This study shows early mechano-sensitization after an acute whiplash injury and the development of further sensitization in patients with long-term disability.
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Peripheral nerve injury produces a persistent neuropathic pain state characterized by spontaneous pain, allodynia and hyperalgesia. In this study, we evaluated the possible involvement of A 2ARs in the development of neuropathic pain and the expression of microglia and astrocytes in the spinal cord after sciatic nerve injury. For this purpose, partial ligation of the sciatic nerve was performed in A 2A knockout mice and wild-type littermates. ⋯ However, a significant decrease of the mechanical allodynia and a suppression of thermal hyperalgesia and allodynia were observed in A 2AR deficient mice. The expression of microglia and astrocytes was enhanced in wild-type mice exposed to sciatic nerve injury and this response was attenuated in knockout animals. Taken together, our results demonstrate the involvement of A 2ARs in the control of neuropathic pain and propose this receptor as an interesting target for the development of new drugs for the management of this clinical syndrome.
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Neuroscience letters · Nov 2008
Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice.
Chronic treatment with vincristine (VCR) causes mechanical allodynia as an adverse effect. We previously reported that peripheral macrophage-derived interleukin-6 played a critical role in VCR-induced allodynia. However, the involvement of glial cell activation and central sensitization in VCR-induced allodynia is still unclear. ⋯ The immunoreactivity of TNF-alpha was co-localized in some of the activated microglia and astrocytes. In behavioral analysis, a neutralizing antibody of TNF-alpha, which was injected intrathecally on days 0, 3, and 6, significantly attenuated VCR-induced mechanical allodynia on days 4 and 7. These results suggest that VCR treatments elicited the activation of glial cells in spinal cord, and up-regulated TNF-alpha in these cells may play an important role in VCR-induced mechanical allodynia.
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Carriers of a particular haplotype of the GTP cyclohydrolase gene (GCH1) had less pain after surgery for chronic lumbar radiculopathy and a decreased sensitivity to some experimental mechanical pain stimuli. Ex-vivo, GCH1 upregulation and BH4 production after forskolin stimulation were reduced, while baseline BH4 concentrations were not affected. This suggested that the haplotype may mainly exert its modulating function when the GCH1 system is provoked. The present study aimed at (i) testing this hypothesis and (ii) independently reproducing the pain-decreasing effects of a particular GCH1 haplotype having been previously associated with pain protection. ⋯ This study verifies previous results that decreased GCH1 function or inducibility as a result of genetic polymorphisms protects against pain. This study extents previous results by showing that this pain protection is mainly conferred under conditions of hyperalgesia resulting from sensitization, supporting specific functions of BH4 in relation to particular aspects of pain.
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In the present study, we used the electronic version of the von Frey test to investigate the role of cytokines (TNF-alpha and IL-1beta) and chemokines (KC/CXCL-1) in the genesis of mechanical hypernociception during antigen-induced inflammation in mice. The nociceptive test consisted of evoking a hindpaw flexion reflex with a hand-held force transducer (electronic anesthesiometer) adapted with a 0.5 mm(2) polypropylene tip. The intraplantar administration of methylated bovine serum albumin (mBSA) in previously immunized (IM), but not in sham-immunized (SI) mice, induced mechanical hypernociception in a dose-dependent manner. ⋯ Antigen-induced hypernociception was reduced by indomethacin and guanethidine and abolished by the two drugs combined. Together, these results suggest that inflammation associated with an adaptive immune response induces hypernociception that is mediated by an initial release of TNF-alpha, which triggers the subsequent release of IL-1beta and KC/CXCL1. The latter cytokines in turn stimulate the release of the direct-acting final mediators, prostanoids and sympathetic amines.