Spinal Cord Stimulation Reduces Mechanical Hyperalgesia and Glial Cell Activation in Animals with Neuropathic Pain

Abstract

Spinal cord stimulation (SCS) is used to manage chronic intractable neuropathic pain. We examined parameters of SCS in rats with spared nerve injury by modulating frequency (4Hz vs. 60Hz), duration (30m vs. 6h), or intensity (50%, 75%, or 90% MT). To elucidate potential mechanisms modulated by SCS, we examined immunoreactivity glial markers in the spinal cord after SCS). An epidural SCS lead was implanted in the upper lumbar spinal cord. Animals were tested for mechanical withdrawal threshold (MWT) of the paw before and 2 weeks after SNI, before and after SCS daily for 4 days, and for 9 days after SCS. Seperate groups of animals were tested for glial immunoreactivity after 4 days of 6h SCS. All rats showed a decrease in MWT 2 weeks after nerve injury and an increase in glial activation. For frequency, 4Hz or 60Hz SCS reversed the MWT when compared to sham SCS. For duration, 6h of SCS showed a greater reduction in MWT when compared to 30 min. For intensity, 90% MT was greater than 75% MT and both were greater than 50% MT or sham SCS. SCS decreased glial activation (GFAP, MCP-1 and OX-42) in the spinal cord dorsal horn when compared to sham. In conclusion, 4Hz and 60Hz SCS for a 6h at 90% MT were the most effective parameters for reducing hyperalgesia, suggesting parameters of stimulation are important for effectiveness of SCS. SCS reduced glial activation at the level of the spinal cord suggesting reduction in central excitability.

Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation

“…Nevertheless, clinically, these results are indicative of an effective treatment. The behavioral results are consistent with previous studies, 12,13 done under different stimulation conditions, allowing us to draw connections between genetic changes and behavioral responses regarding injury status and SCS-induced analgesia.…”

Spinal cord stimulation (scs) improves decreased physical activity induced by nerve injury.

“…This is the first study to show the long-term effectiveness of SCS with repeated treatment and to show improvements in physical activity. Prior studies have shown that a single treatment or treatment for 4 -5 days reduces mechanical hyperalgesia of the paw after nerve injury in multiple models (Guan et al, 2010;Maeda et al, 2009;Smits et al, 2006;Song, Ansah, Meyerson, Pertovaara, & Linderoth, 2013;Truin et al, 2011;Sato et al, 2013;Sato et al, 2014). The magnitude of the reduction varies considerably between studies, with some reports showing nearly complete reversal and others showing a smaller reversal.…”

“…We recently showed that 4 days of SCS, both 4 and 60 Hz, reduces SNI-induced glial cell activation (Sato et al, 2014). SCS has been used for more than 30 years to treat chronic pain, particularly neuropathic pain (Gybels & Sweet, 1989).…”

Spinal Cord Stimulation 50 Years Later

“…6,7 These include central mechanisms of cortical reorganization, 57-59 inhibition of neural conduction at the dorsal horn and supraspinal structures, 56,[60][61][62][63] GABAergic and endogenous opioid receptor activation, 61,64,65 attenuation of wide dynamic range neuronal excitability and decreased glial cell activation, 66,67 and sympathetic nervous system inactivation with resultant improvements in peripheral circulation. 68,69 Successful treatment with SCS is more than a dichotomous "yes" or "no" assessment for pain or the attainment of an arbitrary 50% analgesia.…”