Inhibition of cortical somatosensory processing during and after low frequency peripheral nerve stimulation in humans.

OBJECTIVE: Transcutaneous low-frequency stimulation (LFS) elicits long-term depression-like effects on human pain perception. However, the neural mechanisms underlying LFS are poorly understood. We investigated cortical activation changes occurring during LFS and if changes were associated with reduced nociceptive processing and increased amplitude of spontaneous cortical oscillations post-treatment. METHODS: LFS was applied to the radial nerve of 25 healthy volunteers over two sessions using active (1 Hz) or sham (0.02 Hz) frequencies. Changes in resting electroencephalography (EEG) and laser-evoked potentials (LEPs) were investigated before and after LFS. Somatosensory-evoked potentials were recorded during LFS and source analysis was carried out. RESULTS: Ipsilateral midcingulate and operculo-insular cortex source activity declined linearly during LFS. Active LFS was associated with attenuated long-latency LEP amplitude in ipsilateral frontocentral electrodes and increased resting alpha (8-12 Hz) and beta (16-24 Hz) band power in electrodes overlying operculo-insular, sensorimotor and frontal cortical regions. Reduced ipsilateral operculo-insular cortex source activity during LFS correlated with a smaller post-treatment alpha-band power increase. CONCLUSIONS: LFS attenuated somatosensory processing both during and after stimulation. SIGNIFICANCE: Results further our understanding of the attenuation of somatosensory processing both during and after LFS.

Effects of external trigeminal nerve stimulation (eTNS) on laser evoked cortical potentials (LEP): A pilot study in migraine patients and controls.

Background Transcutaneous external supraorbital nerve stimulation has emerged as a treatment option for primary headache disorders, though its action mechanism is still unclear. Study aim In this randomized, sham-controlled pilot study we aimed to test the effects of a single external transcutaneous nerve stimulation session on pain perception and cortical responses induced by painful laser stimuli delivered to the right forehead and the right hand in a cohort of migraine without aura patients and healthy controls. Methods Seventeen migraine without aura patients and 21 age- and sex-matched controls were selected and randomly assigned to a real or sham external transcutaneous nerve stimulation single stimulation session. The external transcutaneous nerve stimulation was delivered with a self-adhesive electrode placed on the forehead and generating a 60 Hz pulse at 16 mA intensity for 20 minutes. For sham stimulation, we used 2 mA intensity. Laser evoked responses were recorded from 21 scalp electrodes in basal condition (T0), during external transcutaneous nerve stimulation and sham stimulation (T1), and immediately after these (T2). The laser evoked responses were analyzed by LORETA software. Results The real external transcutaneous nerve stimulation reduced the trigeminal N2P2 amplitude in migraine and control groups significantly in respect to placebo. The real stimulation was associated with lower activity in the anterior cingulate cortex under trigeminal laser stimuli. The pattern of LEP-reduced habituation was reverted by real and sham transcutaneous stimulation in migraine patients. Conclusions The present results could suggest that the external transcutaneous nerve stimulation may interfere with the threshold and the extent of trigeminal system activation, with a mechanism of potential utility in the resolution and prevention of migraine attacks.

Changes in laser-evoked potentials during hypnotic analgesia for chronic pain: a pilot study.

BACKGROUND: Hypnotic analgesia is one of the most effective nonpharmacological methods for pain control. Hypnosis and distraction of attention from pain might share similar mechanisms by which brain responses to painful stimulation could be similarly reduced in both states. There is ample evidence for the efficacy of clinical hypnosis as a psychological intervention in the treatment of acute or chronic pain. Results are conflicting, however, with some studies showing an increase, others a reduction, and others still no change in the amplitude of event-related brain potentials during hypnosis as compared to control conditions. Here we compared the effects of clinical hypnosis to simple distraction of attention during recording of laser-evoked potentials (LEPs) in patients with chronic pain. METHODS: The dominant hand in ten patients with chronic pain was tested with LEPs during: (I) resting state; (II) clinical hypnosis, and (III) distraction of attention. Nociceptive responses elicited by LEPs were graded on a numerical rating scale (NRS), and the change in N2-P2 complex amplitude during the three experimental conditions was analyzed. RESULTS: N2-P2 amplitudes were significantly decreased during the hypnotic state as compared to the resting state and distraction of attention. CONCLUSIONS: Hypnosis is a modified state of consciousness that may differ from mental relaxation or distraction of attention from pain. A reduction in N2-P2 amplitude may result from the modulation of diverse brain networks, particularly the frontolimbic pathways, which could modify noxious stimuli input processing during hypnotic analgesia. Our findings indicate that several different brain mechanisms may act together in hypnosis and distraction of attention during pain processing and that clinical hypnosis may provide a useful non-invasive pain relief therapy.

Abdominal acupuncture reduces laser-evoked potentials in healthy subjects.

OBJECTIVE: Acupuncture is known to reduce clinical pain, although the exact mechanism is unknown. The aim of the current study was to investigate the effect of acupuncture on laser-evoked potential amplitudes and laser pain perception. METHODS: In order to evaluate whether abdominal acupuncture is able to modify pain perception, 10 healthy subjects underwent a protocol in which laser-evoked potentials (LEPs) and laser pain perception were collected before the test (baseline), during abdominal acupuncture, and 15 min after needle removal. The same subjects also underwent a similar protocol in which, however, sham acupuncture without any needle penetration was used. RESULTS: During real acupuncture, both N1 and N2/P2 amplitudes were reduced, as compared to baseline (p<0.01). The reduction lasted up to 15 min after needle removal. Furthermore, laser pain perception was reduced during real acupuncture, although the difference was marginally significant (p=0.06). CONCLUSIONS: Our results show that abdominal acupuncture reduces LEP amplitude in healthy subjects. SIGNIFICANCE: Our results provide a theoretical background for the use of abdominal acupuncture as a therapeutic approach in the treatment of pain conditions. Future studies will have to be conducted in clinical painful syndromes, in order to confirm the analgesic effect of acupuncture in patients suffering from pain.

Shaping thalamo-cortical plasticity: a marker of cortical pain integration in patients with post-anoxic unresponsive wakefulness syndrome?

BACKGROUND: The distinctive feature of unresponsive wakefulness syndrome (UWS) is the dissociation between arousal and awareness. Cortico-cortical and thalamo-cortical connectivity and plasticity play a key role in consciousness. UWS patients do not usually show any "cortical" behavioral sign in response to painful stimulation. Nevertheless a "focal conscious" pain perception has been hypothesized. HYPOTHESIS: Since defective plasticity and connectivity within pain matrix could be striking mechanisms of non-conscious pain perception and, consequently, of non-cortical responses in UWS subjects, aim of our study was to investigate pain-motor plasticity in such patients through a specific paired laser associative stimulation protocol (L-PAS). METHODS: We enrolled 10 post-anoxic subjects and 10 healthy controls evaluating clinical and electrophysiological parameters before and after the application of such protocol. RESULTS: Some patient showed a restored pain-motor integration with a partial motor cortex excitability modification. CONCLUSIONS: Although we studied a small cohort of post-anoxic UWS patients and the results obtained were short-lasting, L-PAS seems a feasible and suitable technique in order to induce plastic change within pain matrix in some UWS patients, allowing the production of "cortical" responses to painful stimuli, which are signs of at least partially ("focal") preserved consciousness. Cortico-thalamic plasticity could have also an important role in the emergence of pain perception as compared to other sensory modalities.