Frequency dependent reduction in cutaneous and muscle hyperalgesia by bi-polar spinal cord stimulation in an animal model of nerve injury

Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. Clinically, SCS is applied at frequencies of 60-100Hz with a pulse width of 100-500µs and an intensity 70-90% motor threshold which results in paresthesia in the area of neuropathic pain. However, the most effective parameters have not been systematically investigated. To establish an animal model of SCS, we examined effects of frequency on cutaneous and muscle hyperalgesia induced by neuropathic pain using the spared nerve injury model. Sprague-Dawley rats were anesthetized, the tibial and common peroneal nerves tightly ligated, and a SCS lead, designed for rats similar to that used in humans, implanted in the upper lumber spinal cord epidurally. SCS was delivered using a clinically available neuro-stimulator (model; #37021 and programmer model; #8840, Medtronic) daily for 4 days at one of 4 different frequencies (4Hz, 60Hz, 100Hz, and 250Hz) 2 weeks after nerve injury and compared to sham SCS. Mechanical withdrawal threshold of the paw (von Frey filaments) and compression withdrawal threshold of the hamstring muscles (tweezer) were measured before and after SCS each day. All rats showed a decrease in withdrawal threshold of the paw and the muscle 2 weeks after nerve injury. Treatment with either 4Hz or 60Hz SCS significantly reversed the decreased withdrawal threshold of the paw and the muscle. The reversal of thresholds of the paw and muscle on the 4th day was greater compared to the first treatment.Treatment with 100Hz, 250Hz or sham SCS had no significant effect on the decreased withdrawal threshold of the paw or the muscle that normally occurs after nerve injury. In conclusion, SCS at 4Hz and 60Hz was more effective in reducing hyperalgesia than higher frequencies of SCS (100Hz and 250Hz); and repeated treatments result in a cumulative reduction in hyperalgesia. Supported by Medtronic, Inc.