The Effect of Spinal Cord Stimulation on Spinal Dorsal Horn Lipid Expression in Experimental Painful Diabetic Polyneuropathy: A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Imaging Study

Objectives: Diabetes-induced peripheral nerve fiber damage can cause painful diabetic polyneuropathy (PDPN), induced by central sensitization through proinflammatory processes in the spinal dorsal horn. Disturbances in spinal dorsal horn lipid metabolism play a major role in proinflammatory regulation. Conventional (Con)-spinal cord stimulation (SCS) is an alternative treatment for pain relief in PDPN, whereas differential target multiplexed (DTM)-SCS could be more effective than Con-SCS, specifically targeting the spinal inflammatory response. We hypothesize that Con- and DTM-SCS differentially affect lipid metabolism in the spinal cord of PDPN animals. To study pain relief mechanisms, we analyzed lipid expression in the spinal dorsal horn using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry imaging (MSI). Material and Methods: Diabetes was induced through streptozotocin (STZ) injection in 28 rats, of which 12 developed PDPN. These and four nondiabetic animals (sham STZ) were implanted with a quadripolar lead and stimulated with Con-, DTM-, or Sham-SCS for 48 hours. Mechanical sensitivity was assessed using Von Frey filaments after 24 and 48 hours. After 48 hours of SCS, the spinal cord was collected, and lipids were analyzed using MALDI-TOF MSI. Results: STZ-induced hypersensitivity in the hind paws was reduced by Con- and DTM-SCS. PDPN induction decreased the expression of a glycosphingolipid in laminae 3 of the spinal dorsal horn. After 48 hours of Con- and DTM-SCS, expression levels of several lipids in the spinal dorsal horn decreased, including (HexCer 36:1;O, 40:1;O3), diacylglycerophosphocholines (PC 36:1, 38:6, 40:5), and diacylglycerophosphoserines (PS 36:4). Conclusions: Both Con- and DTM-SCS provide pain relief and decrease spinal dorsal horn lipid expression of PDPN animals, highlighting the complex effects of SCS on the spinal cord physiology. STZ-induced PDPN has a limited effect on lipid expression in the spinal dorsal horn.