This study, co-authored by an international group of researchers, including scientists from Bio2Q, reveals how lysophosphatidic acid (LPA) drives the development of mirror-image pain by propagating inflammatory signaling across the brain through the corpus callosum.

While pain following stroke is typically confined to the side of the body opposite the brain lesion, some patients develop bilateral hypersensitivity, including pain on the unaffected side. The mechanisms underlying this phenomenon have remained poorly understood, however. Using a mouse model of central post-stroke pain, these researchers combined imaging mass spectrometry, pharmacological interventions, and chemogenetic approaches to show that LPA produced at the site of ischemic injury activates microglia within the corpus callosum, triggering inflammatory signaling that spreads to the opposite hemisphere. This process promoted prostaglandin E₂ production in the contralateral insular cortex and activation of the anterior cingulate cortex, ultimately driving bilateral pain hypersensitivity. Importantly, inhibiting either LPA synthesis or microglial activation significantly reduced mirror-image pain, highlighting the therapeutic potential of targeting this inflammatory pathway.

By identifying a previously unrecognized transcallosal neuroinflammatory circuit, this study provides new mechanistic insight into central post-stroke pain and suggests that modulation of LPA signaling and microglial activity may offer new treatment strategies for widespread pain disorders.