Articles: neuropathic-pain.
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When the nerve tissue is injured, endogenous agonist of melanocortin type 4 (MC4) receptor, α-MSH, exerts tonic pronociceptive action in the central nervous system, contributing to sustaining the neuropathic pain state and counteracting the analgesic effects of exogenous opioids. With the intent of enhancing opioid analgesia in neuropathy by blocking the MC4 activation, so-called parent compounds (opioid agonist, MC4 antagonist) were joined together using various linkers to create novel bifunctional hybrid compounds. Analgesic action of four hybrids was tested after intrathecal (i.t.) administration in mouse models of acute and neuropathic pain (chronic constriction injury model, CCI). ⋯ Opioid receptor antagonists and MC4 receptor agonists diminished the analgesic action of these two hybrids studied, though the extent of this effect differed between the hybrids; this suggests that linker is of key importance here. Further results indicate a significant advantage of hybrid compounds over the physical mixture of individual pharmacophores in their analgesic effect. All this evidence justifies the idea of synthesizing a bifunctional opioid agonist-linker-MC4 antagonist compound, as such structure may bring important benefits in neuropathic pain treatment.
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Some patients with chronic pain and implanted spinal cord stimulators or intrathecal (IT) pumps fail to obtain significant pain relief. The use of dual modality treatment with both therapies is understudied. This study evaluated comprehensive outcomes in this patient population and reported outcomes primarily using IT ziconotide. ⋯ Dual modality therapy is a potential treatment option in patients who have lost efficacy with a single neuromodulation modality. Further study is required to identify potential responders and nonresponders.
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Randomized Controlled Trial
High Frequency (HF10) Spinal Cord Stimulation for Chronic Neuropathic Pain.
Spinal cord stimulation (SCS) is well established treatment. In a prospective randomised controlled trial, novel 10-kHz High-frequency Therapy (HF10 Therapy) was superior to traditional low-frequency SCS for the treatment of chronic back and leg pain. ⋯ The patient reported 90% pain reduction at follow-up. Thoracic HF10 SCS is effective modality in managing chronic neuropathic pain.
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Chronic, focal, neuropathic pain is difficult to treat. Local nerve blocks are either ineffective or do not last. Regular neuromodulation modalities like spinal cord stimulation (SCS) or pain pump are invasive and affect a larger area. ⋯ Peripheral neuromodulation using peripheral nerve field stimulation (PNFS) is an effective, minimally invasive, targeted method of treatment. It is a relatively new modality in the field of neuromodulation but is used more often.
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Journal of neurotrauma · Nov 2020
Red-light (670 nm) therapy reduces mechanical sensitivity and neuronal cell death, and alters glial responses following spinal cord injury in rats.
Individuals with spinal cord injury (SCI) often develop debilitating neuropathic pain, which may be driven by neuronal damage and neuroinflammation. We have previously demonstrated that treatment using 670 nm (red) light irradiation alters microglia/macrophage responses and alleviates mechanical hypersensitivity at 7 days post-injury (dpi). Here, we investigated the effect of red light on the development of mechanical hypersensitivity, neuronal markers, and glial response in the subacute stage (days 1-7) following SCI. ⋯ This effect was accompanied by significantly reduced neuronal cell death, reduced astrocyte activation, and reduced iNOS expression in IBA1+ cells at the level of the injury. However, myelin and NF200 immunoreactivity and IL-1β expression in GFAP+ and IBA1+ cells were not altered by red-light treatment. Thus, red-light therapy may represent a useful non-pharmacological approach for treating pain during the subacute period after SCI by decreasing neuronal loss and modulating the inflammatory glial response.