Articles: hyperalgesia-pathology.
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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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Journal of neurotrauma · Nov 2008
Capsular ligament involvement in the development of mechanical hyperalgesia after facet joint loading: behavioral and inflammatory outcomes in a rodent model of pain.
Whiplash injury can produce pain in the neck, arm, and hand, and has been associated with inflammation. However, the relationship between inflammatory responses and pain symptoms remains unknown, hindering the development of appropriate therapeutics for whiplash symptoms. Two joint loading paradigms were used separately in an established rat model of painful cervical facet joint distraction to apply: (1) gross failure, and (2) subfailure distraction of the facet capsular ligament. ⋯ Cytokine mRNA levels in the spinal cord and DRG were also significantly elevated after facet ligament failure, but not after painful subfailure loading. Findings suggest that different joint loading scenarios produced varied inflammatory responses in the CNS. These data support existing clinical reports suggesting that therapeutic interventions directed at the facet capsule may be effective in treating this painful injury.
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The mechanisms of nociception in the low back are poorly understood, partly because systematic recordings from dorsal horn neurons with input from the low back are largely missing. The purpose of this investigation was to (1) identify spinal segments and dorsal horn neurons receiving input from the low back, (2) test the effect of nerve growth factor (NGF) injected into the multifidus muscle (MF) on the neurons' responsiveness, and (3) study the influence of a chronic MF inflammation on the responses. In rats, microelectrode recordings were made in the segments L2, L3, and L5 to find dorsal horn neurons having input from the low back (LB neurons). ⋯ The centers of the neurons' receptive fields (RFs) were consistently located 2-3 segments caudally relative to their recording site. The results show that (1) input convergence from various tissues is common for LB neurons, (2) the input from structures of the low back is processed 2-3 segments cranially relative to the vertebral level of the RFs, and (3) the responsiveness of LB neurons is increased during a pathologic alteration of the MF. The above findings may be relevant for some cases of chronic low back pain in patients.
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Randomized Controlled Trial Comparative Study
Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers.
Cannabinoid-induced analgesia was shown in animal studies of acute inflammatory and neuropathic pain. In humans, controlled clinical trials with Delta-tetrahydrocannabinol or other cannabinoids demonstrated analgesic efficacy in chronic pain syndromes, whereas the data in acute pain were less conclusive. Therefore, the aim of this study was to investigate the effects of oral cannabis extract in two different human models of acute inflammatory pain and hyperalgesia. ⋯ To conclude, no analgesic or antihyperalgesic activity of cannabis extract was found in the experiments. Moreover, the results even point to the development of a hyperalgesic state under cannabinoids. Together with previous data, the current results suggest that cannabinoids are not effective analgesics for the treatment of acute nociceptive pain in humans.
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Cation chloride co-transporters are important determinants for the efficacy of inhibitory neurotransmission in the spinal cord and alterations in their expression levels contribute to allodynia and hyperalgesia associated with neuropathy. However, it remains unknown whether these co-transporters contribute to chronic inflammatory pain. We investigated the expression of potassium-chloride co-transporter 2 (KCC2) and sodium-potassium-chloride co-transporter 1 (NKCC1) in the rat spinal cord after peripheral inflammation induced by complete Freund's adjuvant (CFA) injection. ⋯ Moreover, intrathecal injection of KCC2 antisense oligodeoxynucleotides into naïve rats reduced KCC2 expression in the spinal cord, leading to behavioral hypersensitivity similar to the hyperalgesia induced by peripheral inflammation. Taken together, these results indicate that peripheral inflammation induces downregulation of KCC2 in the dorsal horn of the spinal cord, which may in turn facilitate the development and/or maintenance of chronic inflammatory pain. The data also support the notion that disinhibition in the spinal cord is a general feature of inflammatory and neuropathic pain conditions, and suggest new therapeutic intervention.