High-frequency spinal cord stimulation (10 kHz) alters sensory function and nerve fiber density in painful diabetic neuropathy: a pilot prospective open-label study.

OBJECTIVE: Spinal cord stimulation at 10 kHz has provided effective pain relief and improved function in painful diabetic peripheral neuropathy. This study aims to confirm the clinical outcomes for 10-kHz spinal cord stimulation treatment of painful diabetic peripheral neuropathy and explore its impact on objective quantitative measures of nerve pathology and function. METHODS: This single-academic center, prospective, open-label, observational study examined the pain relief success of 10-kHz spinal cord stimulation in patients >18 years of age with diabetic peripheral neuropathy. Patients underwent skin biopsies to measure intra-epidermal nerve fiber densities and corneal confocal microscopy measurements before implantation and at the 3-, 6-, and 12-month follow-up visits. Numerical rating scale for pain, visual analog scale, neuropathy pain scale, Short Form-36, and Neuropen (pin prick and monofilament) assessments were also conducted. RESULTS: Eight patients met the criteria and were enrolled in the study. A successful trial was achieved in 7 subjects, and 6 completed the study. Significant pain relief (P < .001) was achieved at all follow-up visits. Neurological assessments showed reduced numbers of "absent" responses and increased "normal" responses from baseline to 12 months. Both proximal and distal intra-epidermal nerve fiber densities were higher at 12 months than at baseline (P < .01). Confocal microscopy measurements showed a steady increase in nerve density from baseline (188.8% increase at 12 months; P = .029). CONCLUSIONS: We observed pain relief and improvements in sensory function after stimulation that were accompanied by increases in lower-limb intra-epidermal nerve fiber density and corneal nerve density. Further evaluation with a blinded and controlled study is needed to confirm the preliminary findings in this study.

Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors.

A series of 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinolines was synthesized and these compounds were evaluated for their PNMT inhibitory potency and affinity for the alpha2-adrenoceptor. 7-Nitro-, 7-bromo-, 7-aminosulfonyl-, or 7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs that possess a 3-alkyl substituent that is longer than a methyl group showed decreased PNMT inhibitory potency, except for 3-propyl-7-aminosulfonyl-THIQ, which displayed excellent PNMT inhibitory potency. The rank order for selectivity (PNMT vs the alpha2-adrenoceptor) is 3-alkyl-7-aminosulfonyl-THIQs congruent with 3-alkyl-7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs>3-alkyl-7-nitro-THIQs>3-alkyl-7-bromo-THIQs.