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Pain Med. 2017 May 1;18(5):932-946. doi: 10.1093/pm/pnw144.

Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.

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Center for Nursing Science and Clinical Inquiry, Landstuhl Regional Medical Center, Landstuhl, Germany.
Anatomy, Physiology & Genetics, The Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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.
Daniel K. Inouye Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Lite Cure, LLC, Newark, Delaware, USA.
St. Mary's College of Maryland, St. Mary's City, MD, USA.



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.


Inflammation; Macrophage; Microglia; Neuropathic Pain; Photobiomodulation; Spared Nerve Injury

[Indexed for MEDLINE]

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