Calcium channel α2δ1 proteins mediate trigeminal neuropathic pain states associated with aberrant excitatory synaptogenesis

Autor: Yanhui Peter Yu, Bin Lin, Oswald Steward, Chun-Yi Zhou, Doo-sik Kim, Kang-Wu Li, Kelli Sharp, Z. David Luo
Rok vydání: 2014
Předmět:
Male
Molecular Pharmacology
Synaptogenesis
Neurodegenerative
Biochemistry
Medical and Health Sciences
Rats
Sprague-Dawley
Trigeminal ganglion
Medicine
2.1 Biological and endogenous factors
Pain Research
Molecular Bases of Disease
Anatomy
Biological Sciences
L-Type
Trigeminal Ganglion
Neuropathic pain
Neurological
Excitatory postsynaptic potential
medicine.symptom
Chronic Pain
Orofacial pain
Biochemistry & Molecular Biology
Calcium Channels
L-Type
Spinal neuron
1.1 Normal biological development and functioning
Pain
Trigeminal Caudal Nucleus
Facial Pain
Animals
Gene Regulation
Dental/Oral and Craniofacial Disease
Molecular Biology
Peripheral Neuropathy
Trigeminal nerve
business.industry
Animal
Neurosciences
Cell Biology
Rats
stomatognathic diseases
Disease Models
Animal
Disease Models
Chemical Sciences
Injury (total) Accidents/Adverse Effects
Neuralgia
Trigeminal Nerve Injuries
Sprague-Dawley
Calcium Channels
business
Neuroscience
Synaptic Plasticity
Zdroj: The Journal of biological chemistry, vol 289, iss 10
ISSN: 1083-351X
Popis: To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2.
Databáze: OpenAIRE
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