Figure 1.

Abnormal Ca²⁺ signals in primary somatosensory (S1) cortex astrocytes cause neuropathic pain and allodynia. Soft touch stimulation (A) and pain stimulation (B) activate touch circuits and pain circuits, respectively. In a model of neuropathic pain induced by sciatic nerve ligation, S1 astrocytes become reactive and exhibit excess Ca²⁺ signaling via type II inositol 1,4,5-trisphosphate receptors (IP₃RII) (C). Reactive astrocytes in the S1 cortex produce synaptogenic molecules such as thrombospondin-1 (TSP-1) and cause excessive, uncontrolled synaptogenesis and network rewiring of S1 circuits (C, arrow), thereby leading to mechanical allodynia.