Cervical radiculopathic
pain is a very common symptom that may occur with
cervical spondylosis.
Mechanical allodynia is often associated with cervical radiculopathic
pain and is inadequately treated with current
therapies. However, the precise mechanisms underlying cervical radiculopathic
pain-associated
mechanical allodynia have remained elusive. Compelling evidence from animal models suggests a role of large-diameter dorsal root ganglion neurons and plasticity of spinal circuitry attached with Aβ fibers in mediating
neuropathic pain. Whether cervical radiculopathic
pain condition induces
plastic changes of large-diameter dorsal root ganglion neurons and what mechanisms underlie these changes are yet to be known. With combination of patch-clamp recording, immunohistochemical staining, as well as behavioral surveys, we demonstrated that upon chronic compression of C7/8 dorsal root
ganglions, large-diameter cervical dorsal root ganglion neurons exhibited frequent spontaneous firing together with hyperexcitability. Quantitative analysis of hyperpolarization-activated
cation current ( Ih) revealed that Ih was greatly upregulated in large dorsal root ganglion neurons from cervical radiculopathic
pain rats. This increased Ih was supported by the enhanced expression of hyperpolarization-activated,
cyclic nucleotide-modulated channels subunit 3 in large dorsal root ganglion neurons. Blockade of Ih with selective antagonist,
ZD7288 was able to eliminate the
mechanical allodynia associated with cervical radiculopathic
pain. This study sheds new light on the functional plasticity of a specific subset of large-diameter dorsal root ganglion neurons and reveals a novel mechanism that could underlie the
mechanical allodynia associated with
cervical radiculopathy.