Topography of microglial activation in sensory- and affect-related brain regions in chronic pain

Abstract

Microglial activation in the spinal cord plays a central role in the development and maintenance of chronic pain after a peripheral nerve injury (PNI). There has not yet been a thorough assessment of microglial activation in brain regions associated with pain and reward. To this end, this study uses a mouse model of neuropathic pain in which the left sciatic nerve of male C57Bl/6J mice is loosely constricted (chronic constriction injury) to assess microglial activation in several brain regions 2 weeks after injury, a time point at which pain hypersensitivity is well established. We found significant microglial activation in brain regions associated with sensory pain transmission and affect, including the thalamus, sensory cortex, and amygdala. Activation was consistently most robust in brain regions contralateral to the side of injury. Brain regions not directly involved in either sensory or affective dimensions of pain, such as the motor cortex, did not display microglial activation. This study confirms that PNI induces microglial activation in regions involved with both sensory and affective components of pain. © 2016 Wiley Periodicals, Inc.

Keywords: RRID:AB_839506; affect; brain; inflammation; microglia activation; neuropathic pain.

Figure 1

Representative brain regions showing upregulation of IBA-1 mRNA following peripheral nerve injury (PNI). Expression levels of the IBA-1 mRNA was measured by qRT-PCR from brain regions both ipsilateral and contralateral to surgery. Data are transformed to relative expression (2^dCT). Error bars show the SEM. Abbreviations: VTA, ventral tegmental area. NAc, nucleus accumbens. **=p<0.01, ***=p<0.001.

Figure 2

Representative brain regions showing changes in microglial morphology following peripheral nerve injury (PNI). A) Representative fluorescent micrographs taken with a 20× objective from contralateral habenula, VTA, and motor cortex sections of sham and PNI animals labeled with IBA-1. Inset represents magnification of larger image. For scale, inset box = 100µm×100µm B) Quantification of average microglial cell body size from sham and PNI groups in select brain regions. Data expressed as box and whiskers plot with whiskers representing minimum and maximum values. Abbreviations: VTA, ventral tegmental area; ipsi, ipsilateral; contra, contralateral. *=p<0.05, **=p<0.01 when compared to ipsilateral side of same group; ##=p<0.01 when compared to contralateral side of sham group.