Comparison of intensity‐dependent inhibition of spinal wide‐dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain

Abstract

Background Spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are thought to reduce pain by activating a sufficient number of large myelinated (Aβ) fibres, which in turn initiate spinal segmental mechanisms of analgesia. However, the volume of neuronal activity and how this activity is associated with different treatment targets is unclear under neuropathic pain conditions. Methods We sought to delineate the intensity-dependent mechanisms of SCS and PNS analgesia by in vivo extracellular recordings from spinal wide-dynamic range neurons in nerve-injured rats. To mimic therapeutic SCS and PNS, we used bipolar needle electrodes and platinum hook electrodes to stimulate the dorsal column and the tibial nerve, respectively. Compound action potentials were recorded to calibrate the amplitude of conditioning stimulation required to activate A-fibres and thus titrate the volume of activation. Results Dorsal column stimulation (50 Hz, five intensities) inhibited the windup (a short form of neuronal sensitization) and the C-component response of wide-dynamic range neurons to graded intracutaneous electrical stimuli in an intensity-dependent manner. Tibial nerve stimulation (50 Hz, three intensities) also suppressed the windup in an intensity-dependent fashion but did not affect the acute C-component response. Conclusions SCS and PNS may offer similar inhibition of short-term neuronal sensitization. However, only SCS attenuates spinal transmission of acute noxious inputs under neuropathic pain conditions. Our findings begin to differentiate peripheral from spinal-targeted neuromodulation therapies and may help to select the best stimulation target and optimum therapeutic intensity for pain treatment.

Electrical stimulation of low-threshold afferent fibers induces a prolonged synaptic depression in lamina II dorsal horn neurons to high-threshold afferent inputs in mice

“…We took advantage of the SNL model, an established surgical model of neuropathic pain that has been used in previous studies to demonstrate the analgesic properties of neurostimulation therapy [17,43,52,54]. We found that 50 Hz Aβ-ES gradually reduced the 1 st amplitudes of C-fiber eEPSC in mice at 1–2 weeks after SNL (n=11).…”

Effects of Combined Electrical Stimulation of the Dorsal Column and Dorsal Roots on Wide-Dynamic-Range Neuronal Activity in Nerve-Injured Rats

“…Previous studies showed that CS at the dorsal column and peripheral nerve inhibit WDR neurons in an intensity-dependent manner (18, 23). Different patterns of CS at moderate stimulus intensity induced significant inhibition of WDR neuronal activity, including windup, in SNL rats.…”

Electrical Stimulation of Dorsal Root Entry Zone Attenuates Wide-Dynamic-Range Neuronal Activity in Rats

“…Inhibition of WDR neuronal activity by dorsal column stimulation may partially contribute to SCS-induced analgesia (16, 17, 20, 27). The current study shows that DREZ stimulation with SCS-like parameters also inhibits WDR neurons as dorsal column stimulation does.…”