Articles: neuropathic-pain.
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Expressional changes of pain-associated genes in primary sensory neurons of DRG are critical for neuropathic pain genesis. DNA methyltransferase (DNMT)-triggered DNA methylation silences gene expression. We show here that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice. ⋯ SIGNIFICANCE STATEMENT In the present study, we reported that DNMT1, a canonical DNA maintenance methyltransferase, is upregulated via the activation of the transcription factor CREB in the injured DRG after peripheral nerve injury. This upregulation was responsible for nerve injury-induced de novo DNA methylation within the promoter and 5'-untranslated region of the Kcna2 gene, reductions in Kcna2 expression and Kv current and increases in neuronal excitability in the injured DRG. Since pharmacological inhibition or genetic knockdown of DRG DNMT1 alleviated nerve injury-induced pain hypersensitivities, DRG DNMT1 contributes to neuropathic pain genesis partially through repression of DRG Kcna2 gene expression.
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Trigeminal neuralgia (TN) is characterized by recurrent attacks of lancinating facial pain in the dermatomal distribution of the trigeminal nerve. TN is rare, affecting 4 to 13 people per 100,000. ⋯ Although there remains a debate surrounding the pathogenesis of TN, neurovascular compromise is the most currently accepted theory. Minimal stimulation caused by light touch, talking, or chewing can lead to debilitating pain and incapacitation of the patient. Pain may occur sporadically, though is primarily unilateral in onset. The diagnosis is typically determined clinically. Treatment options include medications, surgery, and complementary approaches. Anti-epileptic and tricyclic antidepressant medications are first-line treatments. Surgical management of patients with TN may be indicated in those who have either failed medical treatment with at least three medications, suffer from intolerable side-effects, or have non-remitting symptoms. Surgical treatment is categorized as either destructive or non-destructive. Deep brain and motor cortex neuro-modulatory stimulation are off label emerging techniques which may offer relief to TN that is otherwise refractory to pharmacological management and surgery. Still, sufficient data has yet to be obtained and more studies are needed.
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Neuroscience bulletin · Aug 2019
Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion.
Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. ⋯ Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
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Case Reports
Spinal Cord Stimulator Explant and Revision Complicated by Syrinx Formation: A Case Report and Literature Review.
Spinal cord stimulation (SCS) has been shown to be a safe, effective, and drug-free treatment option for many chronic pain conditions including refractory low back pain. The most commonly reported complication of SCS is equipment failure. We report a case of spinal cord injury (SCI) during SCS explant and revision. This 61-year-old female veteran complained of intermittent shock-like sensations 3-4 times a week for three months prior to her clinic visit. The device was initially implanted in 2009 secondary to neurogenic claudication with appropriate relief. The battery was replaced in 2015. Pain Management Service referred the patient to neurosurgery for replacement of the original SCS unit. Immediately following surgery she complained of severe left lower extremity pain concentrated in the medial thigh radiating into the groin and buttock. She also complained of pain, weakness and numbness in both legs (left more than right). Magnetic resonance imaging (MRI) revealed an edematous area in the left spinal cord between T11-T12. The patient was placed on steroids, ketamine infusion for pain control, and MRI the next day showed slight improvement of the edema and she was discharged home. Follow-up MRI two months later revealed mild diminution in the size of the cord edema. Her pre-operative shock-like sensations had not returned. While rare, spinal cord injury can occur and should be identified and managed expeditiously. Our case here reports for the first time an association between SCS explant/revision and syrinx formation.
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Randomized Controlled Trial
Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABAA partial agonist, in humans.
This study investigated the analgesic effects of two doses (15 and 65 mg) of PF-06372865, a novel α2/α3/α5 gamma-aminobutyric acid A (GABAA) subunit selective partial positive allosteric modulator (PAM), compared with placebo and pregabalin (300 mg) as a positive control. ⋯ NCT0223871.