title: Fractalkine signaling in microglia contributes to ectopic orofacial pain following trapezius muscle inflammation.
abstract: Fractalkine (FKN) signaling is involved in mechanical allodynia in the facial skin following trapezius muscle inflammation. Complete Freund's adjuvant (CFA) injection into the trapezius muscle produced mechanical allodynia in the ipsilateral facial skin that was not associated with facial skin inflammation and resulted in FKN but not FKN receptor (CX3CR1) expression, and microglial activation was enhanced in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). Intra-cisterna magna anti-CX3CR1 or anti-interleukin (IL)-1β neutralizing antibody administration decreased the enhanced excitability of Vc and C1-C2 neurons in CFA-injected rats, whereas intra-cisterna magna FKN administration induced microglial activation and mechanical allodynia in the facial skin. IL-1β expression and p38 mitogen-activated protein kinase phosphorylation were enhanced in activated microglia after CFA injection. The excitability of neurons whose receptive fields was located in the facial skin was significantly enhanced in CFA-injected rats, and the number of cells expressing phosphorylated extracellular signal-regulated kinase (pERK) following noxious mechanical stimulation of the facial skin was significantly increased in Vc and C1-C2. We also observed mechanical allodynia of the trapezius muscle as well as microglial activation and increased pERK expression in C2-C6 after noxious stimulation of the trapezius muscle in facial skin-inflamed rats. These findings suggest that FKN expression was enhanced in Vc and C1-C2 or C2-C6 following trapezius muscle or facial skin inflammation, microglia are activated via FKN signaling, IL-1β is released from the activated microglia, and the excitability of neurons in Vc and C1-C2 or C2-C6 is enhanced, resulting in the ectopic mechanical allodynia.
authors: Department of Oral Diagnosis, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
authors: Masaaki
authors: M
authors: Kiyomoto
authors: Masamichi
authors: M
authors: Shinoda
authors: Akiko
authors: A
authors: Okada-Ogawa
authors: Noboru
authors: N
authors: Noma
authors: Kazuo
authors: K
authors: Shibuta
authors: Yoshiyuki
authors: Y
authors: Tsuboi
authors: Barry J
authors: BJ
authors: Sessle
authors: Yoshiki
authors: Y
authors: Imamura
authors: Koichi
authors: K
authors: Iwata
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000008:administration & dosage / Q000378:metabolism*; D002946:Cisterna Magna / Q000187:drug effects / Q000502:physiology; D003872:Dermatitis / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D005157:Facial Pain / Q000188:drug therapy / Q000209:etiology*; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000175:diagnosis / Q000209:etiology; D053583:Interleukin-1beta / Q000008:administration & dosage; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009220:Myositis / Q000139:chemically induced / Q000150:complications; D017288:Pain Threshold / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D023062:Receptors, Interleukin-8A / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C100745:Aif1 protein, rat; D000906:Antibodies; D002135:Calcium-Binding Proteins; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D023062:Receptors, Interleukin-8A; D005620:Freund's Adjuvant
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