title: Neuronal CC chemokines: the distinct roles of CCL21 and CCL2 in neuropathic pain.
abstract: The development of neuropathic pain in response to peripheral nerve lesion for a large part depends on microglia located at the dorsal horn of the spinal cord. Thus the injured nerve initiates a response of microglia, which represents the start of a cascade of events that leads to neuropathic pain development. For long it remained obscure how a nerve injury in the periphery would initiate a microglia response in the dorsal horn of the spinal cord. Recently, two chemokines have been suggested as potential factors that mediate the communication between injured neurons and microglia namely CCL2 and CCL21. This assumption is based on the following findings. Both chemokines are not found in healthy neurons, but are expressed in response to neuronal injury. In injured dorsal root ganglion cells CCL2 and CCL21 are expressed in vesicles in the soma and transported through the axons of the dorsal root into the dorsal horn of the spinal cord. Finally, microglia in vitro are known to respond to CCL2 and CCL21. Whereas the microglial chemokine receptor involved in CCL21-induced neuropathic pain is not yet defined the situation concerning the receptors for CCL2 in microglia in vivo is even less clear. Recent results obtained in transgenic animals clearly show that microglia in vivo do not express CCR2 but that peripheral myeloid cells and neurons do. This suggests that CCL2 expressed by injured dorsal root neurons does not act as neuron-microglia signal in contrast to CCL21. Instead, CCL2 in the injured dorsal root ganglia (DRG) may act as autocrine or paracrine signal and may stimulate first or second order neurons in the pain cascade and/or attract CCR2-expressing peripheral monocytes/macrophages to the spinal cord.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg Freiburg, Germany ; Department of Neuroscience, University of Groningen, University Medical Center Groningen Groningen, Netherlands.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
authors.affiliation: Department of Neuroscience, University of Groningen, University Medical Center Groningen Groningen, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Boddeke
keywords: DRG neurons; LDV vesicles; chemokines; microglia reaction; neuron-microglia signaling; neuropathic pain; regulated release pathway