Articles: neuropathic-pain.
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Both spinal cord infiltrating CD4+ T lymphocytes and microglial CD40 contribute to the maintenance of neuropathic pain-like behaviors induced by spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we sought to investigate the involvement of multiple chemokines in microglial CD40-mediated and CD4+ T lymphocytes-mediated L5Tx-induced sensory hypersensitivity. Spinal cord chemokine expression in CD4 knockout (KO), CD40 KO, and wild type (WT) BALB/c mice was determined at the protein level via multiplex assays and at the RNA level via quantitative real-time PCR. ⋯ Intrathecal administration of CXCL1 in WT mice significantly reduced L5Tx-induced mechanical hypersensitivity. CD40 KO mice also displayed higher levels of Ly6G (neutrophil marker) RNA expression in the lumbar spinal cord post-L5Tx. Altogether, our data suggest that CD4+ T lymphocytes and microglial CD40 mediate their pro-nociceptive effects in part by promoting selected chemokine responses, and more importantly, CXCL1 can play an anti-nociceptive role in peripheral nerve injury-induced neuropathic pain, which is possibly mediated by infiltrating neutrophils.
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The identification of neurobiological markers that predict individual predisposition to pain are not only important for development of effective pain treatments, but would also yield a more complete understanding of how pain is implemented in the brain. In the current study using electroencephalography (EEG), we investigated the relationship between the peak frequency of alpha activity over sensorimotor cortex and pain intensity during capsaicin-heat pain (C-HP), a prolonged pain model known to induce spinal central sensitization in primates. We found that peak alpha frequency (PAF) recorded during a pain-free period preceding the induction of prolonged pain correlated with subsequent pain intensity reports: slower peak frequency at pain-free state was associated with higher pain during the prolonged pain condition. ⋯ Altogether, our findings suggest that pain-free state PAF over relevant sensory systems could serve as a marker of individual predisposition to prolonged pain. Moreover, slowing of PAF in response to prolonged pain could represent an objective marker for subjective pain intensity. Our findings potentially lead the way for investigations in clinical populations in which alpha oscillations and the brain areas contributing to their generation are used in identifying and formulating treatment strategies for patients more likely to develop chronic pain.
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Medicinal chemistry · Feb 2018
ReviewManaging Neuropathic Pain in Multiple Sclerosis: Pharmacological Interventions.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of the plethora of motor and sensory disturbances experienced by sufferers, neuropathic pain is a highly prevalent and debilitating symptom, and at present remains extremely difficult to treat. Common forms of neuropathic pain seen in MS patients include central neuropathic pain, Lhermitte's phenomenon and trigeminal neuralgia, which are all speculated to arise from specific patterns of lesion formation. ⋯ Studies aimed at understanding the mechanisms underlying EAE-induced neuropathic pain and investigating the efficacy of novel pharmacological interventions at the animal level offer an exciting area of future research, and may inform future therapeutic options for MS-associated neuropathic pain.
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Clinical Trial
Stimulation of the L2-L3 Dorsal Root Ganglia Induces Effective Pain Relief in the Low Back.
Chronic low back pain affects millions of people worldwide and can arise through a variety of clinical origins. In the case of failed back surgery syndrome (FBSS), previous surgical procedures can contribute to low back pain that is often unresponsive to intervention. Although spinal cord stimulation (SCS) can be an effective treatment modality, it does not provide sufficient pain relief for some intractable cases. Recently, alternative neuromodulation options have been developed, including dorsal root ganglion (DRG) stimulation. The objective of this report is to further investigate these clinical observations. ⋯ For the studied population, DRG stimulation at the L2-L3 levels was effective at relieving low back pain. These reductions in pain were associated with improvements in quality of life. Thus, DRG stimulation at these levels may be effective for low back pain by recruiting both segmental and nonsegmental neural pathways that are not otherwise accessible via traditional SCS.
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Human brain mapping · Feb 2018
Altered structure and functional connection in patients with classical trigeminal neuralgia.
Classical trigeminal neuralgia (TN) is a specific type of neuropathic orofacial pain of which the plasticity of brain structure and connectivity have remained largely unknown. A total of 62 TN patients were included and referred to MRI scans. Voxel-based morphometry was used to analyze the change of gray matter volume. ⋯ The left hemisphere may be dominant in processing and modulation of TN pain signal. Chronification of TN induces volume changes in brain regions which are associated with emotional or cognitive modulation of pain. Hum Brain Mapp 39:609-621, 2018. © 2017 Wiley Periodicals, Inc.