Articles: neuralgia.
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While numerous studies and patient experiences have demonstrated the efficacy of spinal cord stimulation as a treatment for chronic neuropathic pain, the exact mechanism underlying this therapy is still uncertain. Recent studies highlighting the importance of microglial cells in chronic pain and characterizing microglial activation transcriptomes have created a focus on microglia in pain research. Our group has investigated the modulation of gene expression in neurons and glial cells after spinal cord stimulation (SCS), specifically focusing on transcriptomic changes induced by varying SCS stimulation parameters. ⋯ In contrast, HRP or LRP yielded weak or very weak correlations for these transcriptomes. This work demonstrates that chronic pain and subsequent SCS treatments can modulate microglial activation transcriptomes, supporting previous research on microglia in chronic pain. Furthermore, this study provides evidence that DTMP is more effective than HRP and LRP at modulating microglial transcriptomes, offering potential insight into the therapeutic efficacy of DTMP.
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A decarboxylated form of L-arginine, agmatine, preferentially antagonizes NMDArs containing Glun2B subunits within the spinal cord and lacks motor side effects commonly associated with non-subunit-selective NMDAr antagonism, namely sedation and motor impairment. Spinally delivered agmatine has been previously shown to reduce the development of tactile hypersensitivity arising from spinal nerve ligation. The present study interrogated the dependence of agmatine's alleviation of neuropathic pain (spared nerve injury (SNI) model) on GluN2B-containing NMDArs. ⋯ Additionally, we observed that spinally delivered agmatine, ifenprodil and MK-801 inhibited nociceptive behaviors following intrathecal delivery of NMDA in control mice. By contrast, in GluN2B-deficient mice, MK-801 reduced NMDA-evoked nociceptive behaviors, but agmatine had a blunted effect and ifenprodil had no effect. These results demonstrate that agmatine requires the GluN2B subunit of the NMDA receptor for inhibitory pharmacological actions in pre-clinical models of NMDA receptor-dependent hypersensitivity.
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Although microglia activation plays an important role in the development of nerve injury-induced neuropathic pain, the molecular mechanisms of spinal cord microglia activation in nerve injury are not completely understood. Recently, two injured sensory neuron-derived molecules, colony stimulating factor-1 (CSF-1) and GT1b, were proposed to trigger spinal cord microglia activation, yet their relationship and relative contribution to microglia activation have not been addressed. In the present study, the role of GT1b and CSF-1 in microglia activation and proliferation was characterized. ⋯ Conversely, CSF-1 stimulation induced microglia proliferation with minimal proinflammatory gene induction. Notably, neither GT1b nor CSF-1 induced mechanical hypersensitivity in female mice; however, they induced similar microglial proliferation in both male and female mice. Taken together, our data indicate that injured sensory neuron-derived GT1b and CSF-1 activate spinal cord microglia in concert through distinct activation pathways.
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Spinal cord stimulation (SCS) provides relief for patients suffering from chronic neuropathic pain although its mechanism may not be as dependent on electrical interference as classically considered. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. Here, we observed the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach. ⋯ The development of an injury unbalances the proteome of the local neural tissue, neurons, and glial cells, and shifts the proteomic profile to a pain producing state. This study demonstrates the reversal of the injury-induced proteomic state by applying conventional SCS therapy. Additional studies looking at variations in electrical parameters are needed to optimize SCS.
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Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g., burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain syndromes. ⋯ So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.