By immunohistochemistry, an effect of nerve injury on distribution of alpha-2/delta-1 subunit of L-type calcium channel was investigated in rat's 4th and 5th lumbar dorsal root ganglia (DRGs), trigeminal ganglion (TG), and mesencephalic trigeminal nucleus (Mes5). The immunoreactivity was expressed by 52.2% of DRG neurons and 31.4% of TG neurons in intact animals. These neurons mostly had small-to-medium-sized cell bodies. In the DRG and TG, alpha-2/delta-1 subunit-positive neurons were lightly or moderately stained. However, the number of alpha-2/delta-1 subunit-immunoreactive (-IR) neurons dramatically increased in the ipsilateral DRG at 3-28 days after sciatic nerve transection (75.3-79.5%) and in the ipsilateral TG at 7 days after infraorbital nerve transection (66.3%). The IR density of alpha-2/delta-1 subunit in DRG and TG neurons was also elevated by the transection. In the injured DRG and TG, many sensory neurons with small-to-medium-sized cell bodies were strongly stained. Some large DRG and TG neurons showing strong staining intensity also appeared after the treatment. In the intact Mes5, sensory neurons were mostly devoid of alpha-2/delta-1 subunit-immunoreactivity (0.4%). However, alpha-2/delta-1-IR sensory neurons on the ipsilateral side of the Mes5 dramatically increased at 7 days after masseteric nerve transection (31.3%). A double immunofluorescence method also demonstrated that c-Jun activating transcription factor 3 (ATF3)-positive DRG (98.3-99.9%) and Mes5 (81.8%) neurons mostly co-expressed alpha-2/delta-1 subunit after the nerve injuries. However, alpha-2/delta-1 subunit immunoreactivity was relatively infrequent among ATF3-immunonegative DRG neurons (51.6-74.1%) and Mes5 neurons (<1%). The present study indicates that the nerve injury increases the protein level of alpha-2/delta-1 subunit among several types of axotomized sensory neurons in the spinal and trigeminal nervous systems.
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http://dx.doi.org/10.1159/000477604 | DOI Listing |
Front Pharmacol
November 2024
Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Neuropathic pain (NP) is often caused by diabetic neuropathy, chemotherapy, or spinal cord lesions and is associated with significant economic burden and poor quality of life. Sophisticated etiology and pathology recognized different pharmacologic interventions, and hitherto, the reported analgesic efficacy and safety of guideline-recommended drugs are not satisfactory. Overall, this article reviews the mechanism of αδ ligand, the clinical pharmacokinetics, efficacy, safety and cost-effectiveness of mirogabalin for the treatment of NP, offering clinical perspectives into potential benefits of NP-related syndrome or comorbidities.
View Article and Find Full Text PDFPain Rep
December 2024
Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA. Dr. Lesnak is now with University of Texas at Dallas, Department of Neuroscience, Richardson, TX.
Introduction: Pregabalin, which acts on the αδ-1 subunit of voltage-gated calcium channels, relieves ≥50% of pain in a third of individuals with fibromyalgia. Thus far, preclinical studies of pregabalin have predominantly used male animals.
Objectives: The purpose of our study was to investigate potential sex differences in the analgesic efficacy of pregabalin that may contribute to disparities in human outcomes.
Mol Biol Rep
October 2024
Molecular Biochemistry Lab, Centre for Global Health Research, Saveetha Medical College & Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai, Tamil Nadu, 602105, India.
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View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
October 2024
Department of Surgery, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Location Vrije Universiteit (VU) Medical Center and Academic Medical Centre (AMC), the Netherlands (K.B.R., T.A.R.v.M., N.B., K.K.Y.).
J Neurochem
January 2025
Division of Physiology, Department of Pharmacology, Physiology, and Microbiology, Karl Landsteiner University of Health Sciences, Krems, Austria.
αδ proteins serve as auxiliary subunits of voltage-gated calcium channels and regulate channel membrane expression and current properties. Besides their channel function, αδ proteins regulate synapse formation, differentiation, and synaptic wiring. Considering these important functions, it is not surprising that CACNA2D1-4, the genes encoding for αδ-1 to -4 isoforms, have been implicated in neurological, neurodevelopmental, and neuropsychiatric disorders.
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