• Thomas J de Geus, Glenn Franken, and JoostenElbert A JEAJDepartment of Anesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands; Mental Health and Neuroscience Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht Universit.
• Department of Anesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands; Mental Health and Neuroscience Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. Electronic address: t.degeus@maastrichtuniversity.nl.
• Neuromodulation. 2024 Dec 1; 27 (8): 133013371330-1337.

ObjectivesSpinal cord stimulation (SCS) is an alternative treatment option for painful diabetic polyneuropathy (PDPN). Differential target multiplexed (DTM)-SCS is proposed to be more effective than conventional (Con)-SCS. Animal studies are essential for understanding SCS mechanisms in PDPN pain relief. Although the Von Frey (VF) test is the gold standard for preclinical pain research, it has limitations. Operant testing using the conditioned place preference (CPP) test provides insights into spontaneous neuropathic pain relief and enhances the translatability of findings. This study aims to 1) use the CPP test to evaluate Con- and DTM-SCS effects on spontaneous neuropathic pain relief in PDPN animals and 2) investigate the correlation between mechanical hypersensitivity alleviation and spontaneous neuropathic pain relief.Material And MethodsDiabetes was induced through streptozotocin injection in 32 rats; 16 animals developed PDPN and were implanted with a quadripolar lead. Rats were conditioned for Con-SCS (n = 8) or DTM-SCS (n = 7), and a preference score compared with sham was determined. After conditioning, a 30-minute SCS protocol was conducted. Mechanical sensitivity was assessed using VF before, during, and after SCS.ResultsThere were no significant chamber preference changes for DTM-SCS (p = 0.3449) or Con-SCS (p = 0.3632). Subgroups of responders and nonresponders were identified with significant increases in preference score for responders for both DTM-SCS (-266.6 to 119.8; p = 0.0238; n = 4) and Con-SCS (-350.7 to 88.46; p = 0.0148; n = 3). No strong correlation between SCS-induced spontaneous neuropathic pain relief and effects on mechanical hypersensitivity in PDPN animals is noted.ConclusionsThe CPP test is a valuable tool to test the efficacy of the pain-relieving potential of various SCS paradigms in PDPN animals. The results of this study show no differences in spontaneous neuropathic pain relief between DTM- and Con-SCS in PDPN animals. Furthermore, there is no correlation between the effect of SCS in spontaneous pain relief and hind paw mechanical hypersensitivity.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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