Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model

Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 +/- 0.13 g; thermal: 3.94 +/- 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKII alpha signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKII alpha signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKII alpha-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKII alpha signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.

Automated summary

Peripheral tissue damage and inflammation can cause neuroplastic changes in somatic pain pathways, leading to chronic pain. Electroacupuncture can relieve chronic inflammatory pain by modulating central pain pathways and suppressing CaMKII alpha-dependent plasticity.