Trans-spinal magnetic stimulation attenuates neuropathic pain caused by spinal cord injury

Current treatments for neuropathic pain are suboptimal, necessitating the search for more effective therapeutics. Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects, and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models. Here, we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta (CaMKKβ)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/suppressor of cytokine signaling-3 (SOCS3) signaling in microglia. Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation. Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia, which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain, thereby suppressing neuroinflammation. The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia. The results suggested that local repetitive trans-spinal magnetic stimulation inhibits spinal neuropathy and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia. This mechanism provides an effective noninvasive treatment for neuropathic pain caused by spinal cord injury.

CaMKKβ/AMPK/SOCS3 signaling; STAT3; chronic constriction injury; mechanical pain sensitivity; microglia; neuroinflammation; neuropathic pain; nuclear factor-κB p65; repetitive trans-spinal magnetic stimulation.