Abnormalities of the Descending Inhibitory Nociceptive Pathway in Functional Motor Disorders.

BACKGROUND: Pain is a common disabling non-motor symptom affecting patients with functional motor disorders (FMD). OBJECTIVE: We aimed to explore ascending and descending nociceptive pathways with laser evoked potentials (LEPs) in FMD. METHODS: We studied a "bottom-up and top-down" noxious paradigm applying a conditioned pain modulation (CPM) protocol and recorded N2/P2 amplitude in 21 FMD and 20 controls following stimulation of both right arm and leg at baseline (BS) (bottom-up), during heterotopic noxious conditioning stimulation (HNCS) with ice test (top-down) and post-HNCS. RESULTS: We found a normal ascending pathway, but reduced CPM response (lower reduction of the N2/P2 amplitude) in FMD patients, by stimulating both upper and lower limbs. The N2/P2 amplitude ratio*100 (between the HNCS and BS) was significantly higher in patients with FMD than HC. CONCLUSIONS: Our results suggest that pain in FMD possibly reflects a descending pain inhibitory control impairment, therefore, providing a novel venue to explore the pathophysiology of pain in FMD. © 2024 International Parkinson and Movement Disorder Society.

Defect of the Endogenous Inhibitory Pain System in Idiopathic Restless Legs Syndrome: A Laser Evoked Potentials Study.

BACKGROUND: Restless legs syndrome (RLS) is a complex sensorimotor disorder. Symptoms worsen toward evening and at rest and are temporarily relieved by movement. Symptoms are perceived as painful in up to 45% of cases, and nociception system may be involved. OBJECTIVES: To assess the descending diffuse noxious inhibitory control in RLS patients. METHODS: Twenty-one RLS patients and twenty age and sex-matched healthy controls (HC) underwent a conditioned pain modulation protocol. Cutaneous heat stimuli were delivered via laser evoked potentials (LEPs) on the dorsum of the right hand (UL) and foot (LL). N2 and P2 latencies, N2/P2 amplitude and pain ratings (NRS) were recorded before (baseline), during, and after a heterotopic noxious conditioning stimulation (HNCS) application. The baseline/HNCS ratio was calculated for both UL and LL. RESULTS: N2 and P2 latencies did not vary between groups at each condition and limbs. Both groups showed a physiological N2/P2 amplitude and NRS reduction during the HNCS condition in UL and LL in comparison to baseline and post conditions (all, P < 0.003). Between-groups comparisons revealed a significant lower amplitude reduction in RLS at the N2/P2 amplitude during the HNCS condition only for LL (RLS, 13.6 µV; HC, 10.1 µV; P = 0.004). Such result was confirmed by the significant difference at the ratio (RLS, 69%, HC, 52.5%; P = 0.038). CONCLUSIONS: The lower physiological reduction during the HNCS condition at LL in RLS patients suggests a defect in the endogenous inhibitory pain system. Further studies should clarify the causal link of this finding, also investigating the circadian modulation of this paradigm. © 2023 International Parkinson and Movement Disorder Society.

Very early and early neurophysiological abnormalities in Guillain-Barré syndrome: A 4-year retrospective study.

BACKGROUND AND PURPOSE: In its initial stages, Guillain-Barré syndrome (GBS) is difficult to identify, because diagnostic criteria may not always be fulfilled. With this retrospective study, we wanted to identify the most common electrophysiological abnormalities seen on neurophysiological examination of GBS patients and its variants in the early phases. METHODS: We reviewed the clinical records of patients admitted to our Neurology Unit with a confirmed diagnosis of GBS. The study sample was divided in two subgroups according to whether the neurophysiological examination was performed: within 7 days (very early group) or within 7-15 days (early group). H reflex, F waves, and motor and sensory conduction parameters were judged abnormal if they were outside the normal range for at least two nerves. We evaluated neurophysiological findings in Miller-Fisher syndrome (MFS) separately. RESULTS: The study sample comprised 36 patients. In GBS, the most frequent abnormal neurophysiological parameter was the bilateral absence of the H reflex, followed by F wave abnormalities. Motor conduction parameters were altered in less than 50% of patients, and even less common were sensory nerve action potential reduction and the "sural-sparing" pattern. In MFS, H reflex was absent bilaterally in 100% of patients, followed by a predominant peripheral sensory involvement, whereas motor conduction parameters were frequently normal. CONCLUSIONS: Bilateral absence of the H reflex is the most sensitive parameter in early diagnosis of GBS and its variants.

Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser-evoked potentials.

BACKGROUND: The 'pain-inhibits-pain' effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser-evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators). METHODS: We applied a CPM protocol in which the test stimulus was laser stimulation and the conditioning stimulus was a cold pressor test. LEPs recordings were obtained from 15 healthy subjects in three different conditions: baseline, during heterotopic noxious conditioning stimulation (HNCS) and post-HNCS. RESULTS: We observed a significant reduction in N2/P2 amplitude during HNCS and a return to pre-test amplitude post-HNCS, whereas the N1 wave remained unchanged during and post-HNCS. CONCLUSIONS: Our results indicate that CPM affects only the medial pain system. The spinothalamic tract (STT) transmits to both the LT and the MT, while the spinoreticulothalamic (SRT) projects only to the MT. The reduction in the amplitude of the N2/P2 complex and the absence of change in the N1 wave suggest that DNIC inhibition on the dorsal horn neurons affects only pain transmission via the SRT, while the neurons that give rise to the STT are not involved. The N1 wave can be a reliable neurophysiological parameter for assessment of STT function in clinical practice, as it does not seem to be influenced by CPM. SIGNIFICANCE: No reports have described the effect of DNIC on lateral and medial pain pathways. We studied the N1 wave and the N2/P2 complex to detect changes during a CPM protocol. We found a reduction in the amplitude of the N2/P2 complex and no change in the N1 wave. This suggests that the DNIC inhibitory effect on dorsal horns neurons affects only pain transmission via the SRT, whereas the neurons that give rise to the STT are not involved.

Effects of safinamide on pain in Parkinson's disease with motor fluctuations: an exploratory study.

Pain is a common and disabling non-motor symptom (NMS) of Parkinson's disease (PD), which occurs through the course of the disease, often unrecognized and undertreated. For this study, we evaluated the efficacy and safety of safinamide to reduce pain in PD patients with motor fluctuations. A total of 13 PD patients with pain receiving safinamide (Xadago®, 100 mg/daily) were prospectively evaluated for 12 weeks. The primary outcome measures were changes in the total score of the King's Pain Scale for Parkinson's Disease (KPPS), Brief Pain Inventory (BPI) Intensity and Interference, and the Numeric Rating Scale (NRS). Secondary outcomes were the proportion of pain responders, changes in the Clinical Global Impression of Change (CGI), the Parkinson's disease Quality of Life 39 (PDQ39), the Unified Parkinson's Disease Rating Scale parts III and IV (UPDRS III and IV), and laser-evoked potentials (LEPs). LEPs were used to assess potential changes in the central processing of nociceptive inputs. The safety profile was evaluated based on the occurrence of treatment-emergent side effects and the dropout rate. After 12 weeks of add-on safinamide therapy, a significant improvement was noted in the primary (KPPS, BPI Intensity and interference, and NRS) and the secondary outcomes (UPDRS III, IV, CGI, and PDQ39). No significant changes in LEP complexes were observed. All patients completed the study and no treatment-emergent side effects were reported. Our preliminary findings suggest that safinamide 100 mg/day may be effective for the management of pain in PD patients with motor fluctuations and is safe. Further randomized controlled trials are needed to confirm its efficacy.

Pain in cervical dystonia: Evidence of abnormal inhibitory control.

INTRODUCTION: Several observations would suggest that dystonic pain is not simply muscular in origin. While ascending nociceptive pathways are normal in cervical dystonia, it is unknown whether descending inhibitory pain pathways are also normal. METHODS: We applied a conditioned pain modulation protocol and concomitantly recorded laser evoked potentials in patients with cervical dystonia (n = 15), blepharospasm (n = 15) and healthy volunteers (n = 15). RESULTS: During the application of a heterotopic noxious conditioning stimulation, patients with cervical dystonia, but not with blepharospasm, lacked the physiological reduction of the perceived intensity of a painful test stimulus as well as of the related evoked potential. This was observed in cervical dystonia patients regardless of the presence of clinical pain. CONCLUSIONS: Our results suggest that pain in CD is not simply muscular in origin but it also possibly reflects a dysfunction of the descending pain inhibitory control, thus providing a novel venue to explore the pathophysiology of pain in CD.

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.