title: Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.
abstract: Neuropathic pain is common and debilitating with limited effective treatments. Macrophage/microglial activation along ascending somatosensory pathways following peripheral nerve injury facilitates neuropathic pain. However, polarization of macrophages/microglia in neuropathic pain is not well understood. Photobiomodulation treatment has been used to decrease neuropathic pain, has anti-inflammatory effects in spinal injury and wound healing models, and modulates microglial polarization in vitro. Our aim was to characterize macrophage/microglia response after peripheral nerve injury and modulate the response with photobiomodulation.
  
  
  
  Adult male Sprague-Dawley rats were randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury + photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25 mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions (output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry characterized macrophage/microglial activation.
  
  
  
  Injured groups demonstrated mechanical hypersensitivity 1-30 days post-operatively. Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. Peripheral nerve injury caused region-specific macrophages/microglia activation along spinothalamic and dorsal-column medial lemniscus pathways. A pro-inflammatory microglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers.
  
  
  
  Photobiomodulation effectively reduced mechanical hypersensitivity, potentially through modulating macrophage/microglial activation to an anti-inflammatory phenotype.
authors: Center for Nursing Science and Clinical Inquiry, Landstuhl Regional Medical Center, Landstuhl, Germany.
authors: Ann
authors: A
authors: Kobiela Ketz
authors: Anatomy, Physiology & Genetics, The Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Kimberly R
authors: KR
authors: Byrnes
authors: Departments of Neuroscience, Uniformed Services University, Bethesda, MD, USA.|Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences , Bethesda, MD , USA.
authors: Neil E
authors: NE
authors: Grunberg
authors: Daniel K. Inouye Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Christine E
authors: CE
authors: Kasper
authors: Daniel K. Inouye Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Lisa
authors: L
authors: Osborne
authors: Lite Cure, LLC, Newark, Delaware, USA.
authors: Brian
authors: B
authors: Pryor
authors: St. Mary's College of Maryland, St. Mary's City, MD, USA.
authors: Nicholas L
authors: NL
authors: Tosini
authors: Anatomy, Physiology & Genetics, The Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Xingjia
authors: X
authors: Wu
authors: Anatomy, Physiology & Genetics, The Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Juanita J
authors: JJ
authors: Anders
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D028022:Low-Level Light Therapy / Q000379:methods*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology*; D009437:Neuralgia / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D059351:Organ Sparing Treatments; D010147:Pain Measurement; D059348:Peripheral Nerve Injuries / Q000276:immunology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
keywords: Inflammation; Macrophage; Microglia; Neuropathic Pain; Photobiomodulation; Spared Nerve Injury