Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects.

Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called "high-PAS", induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as "minimal intensity required to produce F-responses". We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence ("baseline"). In addition, we applied this intensity at + 25%, - 25%, and - 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of "baseline" and "baseline - 25%" levels but not at + 25% or - 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report.

OBJECTIVES: There is no effective evidence-based non-pharmacological treatment for severe neuropathic pain after spinal cord injury (SCI). Paired associative stimulation (PAS) has been used in motor rehabilitation of patients after SCI. In the SCI-PAS protocol for tetraplegic patients, peripheral and central nerve tracts are activated with subject-specific timing, such that ascending and descending signals appear simultaneously at the cervical level. The effect on motor rehabilitation is thought to arise via strengthening of cervical upper and lower motoneuron synapses. We have observed an analgesic effect of PAS on mild-to-moderate neuropathic pain in tetraplegic patients receiving PAS for motor rehabilitation. Here, we applied PAS to a patient with severe drug-resistant neuropathic pain. METHODS: The patient is a 50-year-old man who had a traumatic cervical SCI three years earlier. He has partial paresis in the upper limbs and completely plegic lower limbs. The most severe pain is located in the right upper limb and shoulder region. The pain has not responded to either pharmacological therapy or repetitive-TMS therapy targeted to either primary motor cortex or secondary somatosensory cortex. PAS was targeted to relieve pain in the right upper arm. Peripheral nerve stimulation targeted the median, ulnar, and radial nerves and was accompanied by TMS pulses to the motor representation area of abductor pollicis brevis, abductor digiti minimi, and extensor digitorum communis muscles, respectively. RESULTS: Hand motor function, especially finger abduction and extension, was already enhanced during the first therapy week. Pain decreased at the end of the second therapy week. Pain was milder especially in the evenings. Numerical rating scale scores (evening) decreased 44% and patient estimation of global impression of change was 1, subjectively indicating great benefit when compared to before therapy. Quality of sleep also improved. CONCLUSIONS: The SCI-PAS protocol reduced neuropathic pain in our subject. The mechanism behind the analgesic effect may involve the modulation of nociceptive and sensory neuronal circuits at the spinal cord level. The possibility to use PAS as an adjunct treatment in drug-resistant post-SCI neuropathic pain warrants further investigation and sham-controlled studies. Patients with neuropathic pain due to SCI may benefit from PAS therapy in addition to PAS therapy-induced improvement in motor function.