Pain
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Attentional disruption has been demonstrated using laboratory-induced pain, but has not been reliably established in everyday pain conditions. This study is the first to examine the effect of everyday acute headache on attention. Seventy-five frequent headache sufferers completed a flanker task, n-back task, attentional switching task, and dual task. ⋯ Headache did not, however, alter performance on the dual task, or the size of the attentional switching effect or result in a flanker effect. It must therefore be emphasised that headache pain appears to impair general task performance, irrespective of task complexity, rather than specific attentional mechanisms. Headache pain has an effect on the core cognitive components necessary for the successful completion of tasks, and in particular those involving the updating of the cognitive system.
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Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). ⋯ The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain.
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Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell-cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. ⋯ Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner.
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Sciatica after disc herniation may be associated with compression of spinal nerves, but also inflammatory substances released from the nucleus pulposus (NP) leaking into the spinal canal. Here, in an animal model mimicking clinical intervertebral disc herniation, we investigate the effect of NP on neuronal activity. In anaesthetized Lewis rats, extracellular single-unit recordings of spinal dorsal horn neurons were performed, and the C-fibre responses were examined. ⋯ In accordance with earlier studies, we showed a significant increase in the C-fibre response and an upregulation of the gene expression of interleukin 1β and tumour necrosis factor 180 minutes after application of NP onto the nerve roots. Moreover, based on a polymerase chain reaction array of 84 common inflammatory cytokines at the same time point, we demonstrated a highly significant upregulation of colony-stimulating factor 1 also termed macrophage colony-stimulating factor and Fas ligand. The pronounced upregulation of Csf1 and Fas ligand 180 minutes after application of NP onto the nerve roots suggests that macrophage activation and apoptosis may be involved in pain hypersensitivity and other sensory abnormalities after disc herniation.