Microglia Activation Tracking across Brain Regions over the Development of Neuropathic Pain

Abstract

Neuropathic pain is a chronic, debilitating condition associated with impaired cognitive, affective and sensory dimensions. One of the mechanisms underlying neuropathic pain is neuroinflammation. Microglia are resident macrophages in the central nervous system and plays an important role in setting neuroinflammation during chronic pain conditions. Microglial mechanisms of pain have been broadly studied in the spinal cord. However, brain mapping of microglial activation over the development of neuropathic pain has not been performed. Adult male and female Sprague-Dawley rats (n=4-6/group) were submitted to a chronic constriction injury (CCI) model of neuropathic pain. After mechanical allodynia assessment by von Frey tests, the whole brain tissue was collected prior the surgery (day 0), or after 7 and 28 days. Microglia activation was assessed by CD11b densitometry using immunohistochemistry in brain regions associated with pain (sensory, affective, motor, and reward system areas). Male rats show a strongly activated microglia in somatosensory cortical regions (Insular and dorsolateral-prefrontal cortex) at 7 but not 28 days. However, it shows a sustained CD11b activation in mediodorsal thalamic nuclei and parabrachial nucleus at 7 and 28 days after CCI surgery. Central medial and paraventricular thalamic nucleus show microglia activation only at 28 days. Affective associated regions (anterior cingulate cortex, medial prefrontal cortex and central amygdala) also shown a sustained microglia activation. Brain reward system regions like the ventral tegmental area, nucleus accumbens and substantia nigra displays microglia activation at 7 and 28 days. Neuropathic pain induces widespread microglia activation across the brain. Microglia activation in somatosensory cortex occurs at 7 but not 28 days whilst affective-motivational regions display a sustained or stronger activation. Sensory regions microglia activation could develop rather than maintain neuropathic pain. Long-lasting effective disorders may be associated with microglial activation in affective-motivational encoding regions. NARSAD - YOUNG INVESTIGATOR GRANT from BRAIN & BEHAVIOR RESEARCH FOUNDATION.