**2.5 SCS in a model of painful diabetic neuropathy**

Originally developed in the early 1960's for studying diabetes mellitus, the streptozotocin (STZ)-based painful diabetic neuropathy model (SPDN) uses an antibiotic derived from *Streptomyces achromogenes* to selectively kill insulin secreting β-cells in the pancreas [58]. The results replicate symptoms seen in type 1 diabetes including dysregulation of blood glucose, decreased body weight, and peripheral artery disease leading to painful diabetic neuropathy.

Early investigations with this model to study the effects of SCS were conducted by Wu et al. [59] to explore the effect of SCS on blood flow in the periphery. Adult male rats were divided into two groups: (1) diabetic rats and (2) non-diabetic rats. Diabetic rats were injected with 50 mg/kg streptozotocin i.p., while the nondiabetic animals were injected with an equivalent volume of vehicle (citrate buffer). Animals were monitored weekly for weight loss and blood glucose levels. After four weeks, animals were tested for vasodilation in response to SCS provided via a spring-loaded unipolar ball electrode placed on the right or left side of the subdural face of the dorsal columns at the L2-L3 spinal segments. SCS was set to 50 Hz frequency, 0.2 ms PW, with monophasic rectangular pulses. Current was applied for 2 minutes at 30, 60, or 90% of the MT. It was found that MT in diabetic rats was significantly higher than in non-diabetic rats, and that SCS at the largest intensity attenuated SCS-induced vasodilation in diabetic rats. Furthermore, increasing SCS from 30% to 90% of MT increased blood flow in non-diabetic rats but not in diabetic rats. The study suggested that SCS-induced vasodilation improves peripheral blood flow, although this seems partially impaired in the diabetic animals.

In a later study, van Beek et al. [60] utilized the SPDN model to explore the effect of increasing the stimulation frequency on mechanical hypersensitivity induced by the model. In this study the dosage of STZ was increased to 65 mg/kg, to ensure the development of type-1 diabetes in four days instead of four weeks. Animals were implanted with a quadripolar lead via a T13 laminectomy into the dorsal epidural space of the T10-T12 spinal cord. Stimulation parameters were set to 200 μs PW, intensity at 67% MT and frequency at either 5, 50, or 500 Hz. Shamstimulated animals were used as controls. SCS sessions were 40 minutes/day for four consecutive days. It was found that SCS at all frequencies alleviated mechanical sensitivity similarly, but stimulation at 500 Hz elicited a delayed response.

In other study, van Beek et al. [61] utilized the SPDN model to evaluate the long-term efficacy (10 weeks) of conventional SCS treatment. As before, the SPDN model was induced in male rats using an i.p. injection of 65 mg/kg STZ. Animals were monitored for weight loss and blood glucose to establish response to the model. *Animal Pain Models for Spinal Cord Stimulation DOI: http://dx.doi.org/10.5772/intechopen.96403*

**Figure 5.** *Effect of conventional SCS on mechanical hypersensitivity in a diabetic neuropathic pain model. \* indicates a significant difference (p < 0.05) relative to No-SCS. Values obtained from reference [61].*

An internally implanted pulse generator fitted with a quadripolar lead was required due the longer duration of the study. The quadripolar lead was implanted via a L1 laminectomy into the dorsal epidural space of the L2-L5 spinal cord. Stimulation parameters were 50 Hz frequency, 210 μs PW, intensity at 67% of the MT, 12 h/day for four weeks. A group of implanted SPDN animals sham for SCS were included as a control. The results indicate that long-term conventional SCS decreases mechanical hypersensitivity even after cessation of SCS in the SPDN model (**Figure 5**).
