Daniela Virdis

Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: A laser-evoked potential study

&NA; Charcot‐Marie‐Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser‐evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient‐oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p = 0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p > 0.05). This result is probably due to a length‐dependent A&dgr;‐fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p = 0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the A&dgr; afferents.

Habituation to Pain in “Medication Overuse Headache”: A CO2 Laser-Evoked Potential Study

(Headache 2012;52:792‐807)

Patterns of habituation and clinical fluctuations in migraine

Background Habituation deficit, suggesting a deregulation of cortical excitability, represents a typical hallmark of interictal stages of migraine. We previously demonstrated that several neurophysiological markers of altered cortical excitability are significantly correlated to spontaneous clinical fluctuations of migraine. We therefore aimed at verifying whether clinical fluctuations are correlated to specific patterns of somatosensory evoked potential (SEP) habituation. Methods We analyzed habituation after median nerve stimulation of both high-frequency oscillations (HFOs) and N20 SEP in 25 migraine patients and 18 healthy volunteers. Subjects underwent six consecutive series of 500 stimuli. Results Migraine patients as a whole showed a significant habituation deficit of the N20 response. Moreover, spontaneously worsening patients show a clear potentiation of this wave in the last block of stimuli, whereas in spontaneously improving patients the N20 amplitude remained stable. Presynaptic HFOs were smaller in worsening patients and larger in improving ones, but they did not undergo habituation in patients as well as in healthy subjects. Conclusions Potentiation of the N20 response in spontaneously worsening migraineurs confirms that the reduction of the thalamocortical drive plays a major role in migraine pathogenesis. Moreover, the stable pattern we observed in spontaneously improving patients suggests that compensatory mechanisms can also play an important role. The normal response to repeated stimuli of HFOs in migraineurs might indicate that, although its initial amount depends on clinical conditions, high-frequency thalamocortical drive remains stable during the stimulation and probably reflects the activity of a buffer mechanism.

Pregnancy-induced analgesia: A combined psychophysical and neurophysiological study

To investigate changes in heat pain threshold and modifications in heat pain processing during pregnancy and labour, seventy‐six nulliparous pregnant women were enrolled in two studies.

Somatosensory evoked potentials reflect the upper limb motor performance in multiple sclerosis

OBJECTIVE The aim of this multicentric study was to multidimensionally evaluate the relationship among somatosensory evoked potentials (SEPs) parameters, patients perspective and clinical measures of the upper limb impairment in patients with multiple sclerosis (MS). METHODS We consecutively enrolled 39 MS patients. For median nerve SEPs we acquired the N9, P14, N20 responses and the N9-P14 and P14-N20 interpeak latencies on the dominant side. We also used a validated patient-oriented questionnaire (Disabilities of the Arm, Shoulder and Hand - DASH) and a test of dexterity quantification as the 9-Hole Peg Test (9-HPT). RESULTS A significant longer time to complete the 9-HPT (p<0.00006) was observed in patients with abnormal SEPs. Patients with undetectable N20 or P14 responses performed the 9-HPT in a significant longer time than patients with detectable responses (p<0.0006 and p<0.001 respectively). Concerning the perspective of patient (evaluated with the DASH questionnaire) significant differences in patients with undetectable P14 response (p<0.01) were observed. CONCLUSIONS Our data provide further information useful for interpretation of SEPs results, being the median nerve SEPs related to the upper limb performance in MS patients. SIGNIFICANCE These data increase the significance of SEPs both in clinical practice and in experimental studies in MS.

Evidence of different spinal pathways for the warmth evoked potentials

OBJECTIVE To investigate the presence of multiple spinothalamic pathways for warmth in the human spinal cord. METHODS Laser evoked potentials to C-fiber stimulation (C-LEPs) were recorded in 15 healthy subjects after warmth stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels. This method allowed us to calculate the spinal conduction velocity (CV) in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different C-LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the C-N1 potential, generated in the second somatosensory (SII) area, and the late C-P2 response, generated in the anterior cingulate cortex (ACC). RESULTS The calculated CV of the spinal fibers generating the C-N1 potential (around 2.5m/s) was significantly different (p<0.01) from the one of the pathway producing the P2 response (around 1.4m/s). CONCLUSIONS Our results suggest that the C-N1 and the C-P2 components are generated by two parallel spinal pathways. SIGNIFICANCE Warmth sensation is subserved by parallel spinothalamic pathways, one probably reaching the SII area, the other the ACC.

Impaired pain processing in patients with silent myocardial ischemia.

a Dpt. of Cardiovascular Sciences, Universita Cattolica del Sacro Cuore, Largo F. Vito, 1, Rome, Italy b Neurology Division, Pediatric Hospital “Bambino Gesu” IRCCS, Rome, Italy c Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark d Dpt. of Geriatrics, Neuroscience & Orthopedics, Universita Cattolica del Sacro Cuore, Largo F. Vito, 1, Rome, Italy e Don Carlo Gnocchi Onlus Foundation, Milan, Italy f Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy

P23.5 Cardiac pain: a role for the brain?

Fibromyalgia syndrome is the chronic pain of unknown cause. One of the theories is the symphathetic activation in muscle tissue microcirculation that role in muscle hypoxia. The hypoxia makes the pain on the muscle. It can happen in all ages, female > male. Method: We studied 22 patients (from June 2010 October 2010), consist of 15 female and 7 male. All the patients who came to our clinic had diffuse chronic pain on their musculosceletal complaints. The diagnose were made by following The American College of Rheumatology (1990) criterias. The pain was measured by Verbal Descriptor Scale (before and after treatment). We used MagPro R30 and the setting: Frequency: 15 Hz Pulses: 50 Number of train: 30 Inter train interval: 5 seconds Range of the intensities given from 30% to 40% The coil put on the shoulder, back, low back and also arm areas (where the patients felt the pain). We moved the coil (not static) and the stimulation is given only once (1500 pulses). Results: The study showed: • before treatment (verbal descriptor scale) range 6 10 • after treatment (verbal descriptor scale) range 0 2 Conclusion: Peripheral Magnetic Stimulation is quite efficient for Fibromyalgia Syndrome treatment. This is just the beginning of the study which it showed the significant changes. Perhaps Peripheral Magnetic Stimulation could be using as one of the treatment choice for chronic pain in Fibromyalgia Syndrome. We still need the further study with the bigger samples.

P14-18 Nociceptive processing in pregnancy: a contact heat evoked potential study

Methods: Subjective assessment comprised of the real-time visual analog scale (RT-VAS) while objective assessment cooperating both skin conductance (SC) and heart rate (HR). Results: Our results indicates a disparity in both subjective and objective assessment on direct comparison of placebo vs. non placebo effects on 20 min of whether anticipation of pain and pain. As compared to the nonplacebo group, the placebo intervention effected a reduction in the both subjective and objective measures after sustained 20 min pain. Significant placebo-induced number of fluctuations in the SC (NFSC) reduction was positively correlated with RT-VAS reduction during pain. HR was significantly decreased for the entire 20 min whereas NFSC was decreased only at first 5 and 10 min during anticipation of pain with placebo compared to only anticipation of pain condition. In the grouped high, middle, low and non responder to placebo analgesic effects, both analgesic efficacy of placebo and placebo-induced NFSC reduction was significantly greater in the high responder compared to non responder during pain. Conclusions: These data demonstrated the utility of both subjective and objective measurement in the determination of the analgesic potential placebo can be assessed by subjective measurement of RT-VAS and objective monitoring of SC and HR. In compared to HR, NFSC is more efficient to evaluate objective assessment in placebo analgesic response and have significant correlation with subjective assessment RT-VAS.

P21.15 Evidence of two spinal pathways for warmth in man: a laser evoked potential study

threshold of stimulation in the course of adaptation of her organism to future labour, which is accompanied by protection against influence of strong stimuli. Purpose: Interpretation of headache intensity in pregnant women with preeclampsia. Methods: We assessed intensity of headache (using CPS scale) in 40 pregnant women with preeclampsia. 13 women were diagnosed with “mild preeclampsia”, 15 with “moderate preeclampsia”, and 12 with “severe preeclampsia”. CPS scale gives the following degrees of pain: absence of pain, mild pain, moderate pain, strong pain, and maximal pain. The headache was localized predominantly in frontotemporal and occipital zones (mediated through the system of n.trigeminus and branches of n.glossopharyngeus and n.vagus). Results: We obtained the following headache characteristics: in mild preeclampsia 7 women – absence of pain, 4 women – mild pain, 2 women – moderate pain. In moderate preeclampsia: 4 women – absence of pain, 5 women – mild pain, 6 women – moderate pain. In severe preeclampsia: 2 women – moderate pain, 7 women – strong pain, 3 women – maximal pain. In all cases the headache did not coincide in time with increase of blood arterial pressure. Conclusions: This data reveal the increase in pain barrier along with sensory adaptation to it in pregnant women with mild to moderate preeclampsia. In case of severe preeclampsia takes place decrease in pain barrier along with sensory desadaptation to pain, which reflects overstrain of the body and depletion of mechanisms of adaptation and protection. This should be considered during clinical diagnosing of preeclampsia severity and, particularly, of headache severity in pregnant women.