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Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions.
Eur J Neurosci. 2004 Sep; 20(5):1150-60.EJ

Abstract

Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and neuropathic pain may be partially mediated by spinal cord glial activation and consequent glial proinflammatory cytokine release, there must be a signal released by affected neurons that triggers the activation of glia. We sought to determine whether there is anatomical evidence implicating spinal fractalkine as such a neuron-to-glia signal. We mapped the regional and cellular localization of fractalkine and CX3CR1 in the rat spinal cord and dorsal root ganglion, under basal conditions and following induction of neuropathic pain, employing both an inflammatory (sciatic inflammatory neuropathy; SIN) as well as a traumatic (chronic constriction injury; CCI) model. Fractalkine immunoreactivity and mRNA were observed in neurons, but not glia, in the rat spinal cord and dorsal root ganglia, and levels did not change following either CCI or SIN. By contrast, CX3CR1 was expressed by microglia in the basal state, and the microglial cellular concentration was up-regulated in a regionally specific manner in response to neuropathy. CX3CR1-expressing cells were identified as microglia by their cellular morphology and positive OX-42 and CD4 immunostaining. The cellular distribution of fractalkine and CX3CR1 in the spinal circuit associated with nociceptive transmission supports a potential role in the mechanisms that contribute to the exaggerated pain state in these models of neuropathy.

Authors+Show Affiliations

Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA. Gverge@neurocrine.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15341587

Citation

Verge, Gail M., et al. "Fractalkine (CX3CL1) and Fractalkine Receptor (CX3CR1) Distribution in Spinal Cord and Dorsal Root Ganglia Under Basal and Neuropathic Pain Conditions." The European Journal of Neuroscience, vol. 20, no. 5, 2004, pp. 1150-60.
Verge GM, Milligan ED, Maier SF, et al. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur J Neurosci. 2004;20(5):1150-60.
Verge, G. M., Milligan, E. D., Maier, S. F., Watkins, L. R., Naeve, G. S., & Foster, A. C. (2004). Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. The European Journal of Neuroscience, 20(5), 1150-60.
Verge GM, et al. Fractalkine (CX3CL1) and Fractalkine Receptor (CX3CR1) Distribution in Spinal Cord and Dorsal Root Ganglia Under Basal and Neuropathic Pain Conditions. Eur J Neurosci. 2004;20(5):1150-60. PubMed PMID: 15341587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. AU - Verge,Gail M, AU - Milligan,Erin D, AU - Maier,Steve F, AU - Watkins,Linda R, AU - Naeve,Gregory S, AU - Foster,Alan C, PY - 2004/9/3/pubmed PY - 2004/11/13/medline PY - 2004/9/3/entrez SP - 1150 EP - 60 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 20 IS - 5 N2 - Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. Given that peripheral nerve inflammation and/or injury gives rise to neuropathic pain, and neuropathic pain may be partially mediated by spinal cord glial activation and consequent glial proinflammatory cytokine release, there must be a signal released by affected neurons that triggers the activation of glia. We sought to determine whether there is anatomical evidence implicating spinal fractalkine as such a neuron-to-glia signal. We mapped the regional and cellular localization of fractalkine and CX3CR1 in the rat spinal cord and dorsal root ganglion, under basal conditions and following induction of neuropathic pain, employing both an inflammatory (sciatic inflammatory neuropathy; SIN) as well as a traumatic (chronic constriction injury; CCI) model. Fractalkine immunoreactivity and mRNA were observed in neurons, but not glia, in the rat spinal cord and dorsal root ganglia, and levels did not change following either CCI or SIN. By contrast, CX3CR1 was expressed by microglia in the basal state, and the microglial cellular concentration was up-regulated in a regionally specific manner in response to neuropathy. CX3CR1-expressing cells were identified as microglia by their cellular morphology and positive OX-42 and CD4 immunostaining. The cellular distribution of fractalkine and CX3CR1 in the spinal circuit associated with nociceptive transmission supports a potential role in the mechanisms that contribute to the exaggerated pain state in these models of neuropathy. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/15341587/Fractalkine__CX3CL1__and_fractalkine_receptor__CX3CR1__distribution_in_spinal_cord_and_dorsal_root_ganglia_under_basal_and_neuropathic_pain_conditions_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0953-816X&date=2004&volume=20&issue=5&spage=1150 DB - PRIME DP - Unbound Medicine ER -