Effects of Spinal Cord and Peripheral Nerve Stimulation Reflected in Sensory Profiles and Endogenous Pain Modulation

Abstract

Objectives: Spinal cord and peripheral nerve stimulation (SCS/PNS) may alleviate chronic pain; however, the underlying mechanisms remain controversial. The aim of this observational study was to assess sensory changes in the ON-conditions and OFF-conditions to obtain insights into the mechanism of analgesic effects of SCS/PNS. Materials and Methods: We contacted 85 patients and selected 28 patients with sufficient pain relief by SCS (n=15) or PNS (n=13) to assess their ongoing pain intensity (Numerical Rating Scale, 0 to 10), pain thresholds using Quantitative Sensory Testing (DFNS-protocol), and conditioned pain modulation (CPM) in a nonrandomized manner 2 to 4 hours after SCS/PNS deactivation (OFF-condition) and during stimulation (ON-condition). For each patient, the number of abnormally decreased pain thresholds, the presence of dynamic mechanical allodynia, and/or increased pain sensitivity was additionally totaled OR summed. Results: In the ON-condition, pain intensity decreased (Numerical Rating Scale SCS: 6.5±2.1 vs. 3.7±2.3, P<0.01; PNS: 6.2±1.4 vs. 4±1.9, P<0.01), but this did not correlate with any single sensory parameter. However, for SCS, the total number of parameters indicating hyperalgesia was significantly reduced in the ON-condition (45 vs. 23, P=0.001). A smaller CPM effect in the OFF-condition correlated with a greater CPM improvement during stimulation (SCS: r=−0.741, P=0.002; PNS: r=−0.773, P=0.003), independently from the spontaneous pain intensity. Discussion: The analgesic effect of SCS/PNS did not correlate with changes of single sensory parameters, but SCS/PNS reduced the number of abnormal hyperalgesic findings disregarding the kind of applied stimuli, suggesting a general antihyperalgesic effect. In addition, stimulation improved the endogenous pain inhibition. Both findings indicate that SCS/PNS may modulate central circuits.

Evidence-Based Clinical Guidelines from the American Society of Pain and Neuroscience for the Use of Implantable Peripheral Nerve Stimulation in the Treatment of Chronic Pain

“…10 Furthermore, PNS decreases central sensitization and hyperalgesia by reducing excessive peripheral nociceptive activity in the spinal cord, inhibiting wide dynamic range of neurons in the dorsal horn, and decreasing Aβ fiber-induced activity in the medial lemniscal pathway in the brain. [11][12][13] Additionally, animal research has demonstrated that the analgesic effects of PNS may involve the serotonergic (5HT2, 5HT3), GABAergic, and glycinergic pathways. 14,15 Studies in the peripheral nervous system have demonstrated that PNS disrupts the transmission of nociceptive afferent fibers.…”

Peripheral Nerve Stimulation: The Evolution in Pain Medicine

“…Central mechanisms include inhibition of pain signals from inhibitory dorsal horn interneurons (Gate Control Theory), modulation of wide dynamic range (WDR) neurons in the dorsal horn, and reduction of neural impulses via the medial lemniscal pathway. By inhibiting WDR neurons in the dorsal horn, as well as reducing activity of A-β fibers in the medial lemniscal pathway, PNS may decrease the degree of central sensitization and hyperalgesia [ 16 , 17 ]. Furthermore, in the spinal cord, PNS may affect biochemical pathways, including serotonergic, GABAergic, and glycinergic pathways [ 18 ].…”

Therapeutic Neuromodulation toward a Critical State May Serve as a General Treatment Strategy

“…Diverse neuromodulatory techniques have emerged in contemporary times, some of which remain largely within the domains of basic science, such as optogenetic modulation [ 2 , 3 ], while other methods have seen a massive clinical translation. Indeed, among today’s most well-established neuromodulatory treatments are transcranial magnetic stimulation (TMS) for depression [ 4 ], deep brain stimulation (DBS) of the basal ganglia to alleviate Parkinson’s disease [ 5 ], and spinal cord and peripheral nerve stimulation for chronic pain relief [ 6 ].…”