Articles: neuralgia.
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Neuroscience research · May 2019
Upregulation of Cav3.2 T-type calcium channels in adjacent intact L4 dorsal root ganglion neurons in neuropathic pain rats with L5 spinal nerve ligation.
Besides the injured peripheral dorsal root ganglion (DRG) neurons, the adjacent intact DRG neurons also have important roles in neuropathic pain. Ion channels including Cav3.2 T-type calcium channel in the DRG neurons are important in the development of neuropathic pain. In the present study, we aimed to examine the expression of Cav3.2 T-type calcium channels in the intact DRG neurons in neuropathic pain. ⋯ Western blotting showed that total and membrane protein levels of Cav3.2 in L4 DRG neurons increased, and voltage-dependent patch clamp recordings revealed an increased T-type current density with a curve shift to the left in steady-state activation in the acutely isolated L4 DRG neurons in neuropathic pain rats. Immunofluorescent staining further showed that the membrane expression of Cav3.2 increased in CGRP-, IB4-positive small neurons and NF200-positive large ones. In conclusion, the membrane expression and the function of Cav3.2 T-type calcium channels are increased in the intact L4 DRG neurons in neuropathic pain rats with peripheral nerve injury like SNL.
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While evidence indicates that sigma-1 receptors (Sig-1Rs) play an important role in the induction of peripheral neuropathic pain, there is limited understanding of the role that the neurosteroidogenic enzymes, which produce Sig-1R endogenous ligands, play during the development of neuropathic pain. We examined whether sciatic nerve injury upregulates the neurosteroidogenic enzymes, cytochrome P450c17 and 3β-hydroxysteroid dehydrogenase (3β-HSD), which modulate the expression and/or activation of Sig-1Rs leading to the development of peripheral neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of P450c17, but not 3β-HSD, in the ipsilateral lumbar spinal cord dorsal horn at postoperative day 3. ⋯ Co-administration of the Sig-1R agonist, PRE084 restored the development of mechanical allodynia originally suppressed by the ketoconazole administration. However, ketoconazole-induced inhibition of thermal hyperalgesia was not affected by co-administration of PRE084. Collectively these results demonstrate that early activation of P450c17 modulates the expression and activation of astrocyte Sig-1Rs, ultimately contributing to the development of mechanical allodynia induced by peripheral nerve injury.
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A rat model of neuropathic pain at 6 weeks after spinal nerve ligation (SNL6w) exhibits both mechanical hypersensitivity and impaired noxious stimuli-induced analgesia (NSIA). Repeated treatment with antidepressants can produce antihypersensitivity and restore NSIA. To examine the involvement of a brain-derived neurotrophic factor-mediated mechanism, a tropomyosin receptor kinase B (TrkB) agonist, 7,8-dihydroxyflavone (DHF), was administered to SNL6w rats (5 mg/kg/d for 5 days). ⋯ PERSPECTIVE: This article demonstrates that repeated treatment with TrkB agonist, DHF, restored endogenous analgesia. Repeated amitriptyline treatment showed similar effect via TrkB-mediated mechanisms, and the effect may be independent from the effect of antihypersensitivity. This effect of TrkB activation is promising for patients with chronic pain with impaired descending inhibition.
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Randomized Controlled Trial Comparative Study
Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: Disassembling the percept of pain.
To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study. ⋯ NCT01932905.
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Background and aims Following spinal cord injury (SCI), a majority of individuals may develop neuropathic pain, which further reduces quality of life. Pain is difficult to treat by medication; in fact, medication overuse may aggravate neuropathic pain in SCI by causing central sensitization (CS): a mechanism of hyper-reactivity of the dorsal horn neurons in the spinal cord with amplified cerebral pain response. The purpose of this study was to examine the presence of neuropathic pain and CS above the spinal lesion in SCI, and to investigate whether injury characteristics or medication influenced pain response. ⋯ However, findings regarding SCI subgroup comparison did not support our hypothesis that more medication leads to increased CS. Implications The development of CS may complicate diagnosis and pain treatment following SCI. Prospective studies of SCI with a healthy control group are needed.