Contact Heat Evoked Potentials Amplitude Research Articles

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I.

The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I. Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas. Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort. This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

Is conditioned pain modulation (CPM) affected by negative emotional state?

Conditioned pain modulation (CPM) is an experimental paradigm, which describes the inhibition of responses to a noxious or strong-innocuous stimulus, the test stimulus (TS), by the additional application of a second noxious or strong-innocuous stimulus, the conditioning stimulus (CS). As inadequate CPM efficiency has been assumed to be predisposing for clinical pain, the search for moderating factors explaining inter-individual variations in CPM is ongoing. Psychological factors have received credits in this context. However, research concerning associations between CPM and trait factors relating to negative emotions has yielded disappointing results. Yet, the influence of anxious or fearful states on CPM has not attracted much interest despite ample evidence that negative affective states enhance pain. Our study aimed at investigating the effect of fear induction by symbolic threat on CPM. Thirty-seven healthy participants completed two experimental blocks: one presenting aversive pictures showing burn wounds (high-threat block) and one presenting neutral pictures (low-threat block). Both blocks contained a CPM paradigm with contact heat as TS and hot water as CS; subjective numerical ratings as well as contact-heat evoked potentials (CHEPs) were assessed. We detected an overall inhibitory CPM effect for CHEPs amplitudes but not for pain ratings. However, we found no evidence for a modulation of CPM by threat despite threat ratings indicating that our manipulation was successful. These results suggest that heat/thermal CPM is resistant to this specific type of symbolic threat induction and further research is necessary to examine whether it is resistant to fearful states in general. The attempt of modulating heat conditioned pain modulation (CPM) by emotional threat (fear/anxiety state) failed. Thus, heat CPM inhibition again appeared resistant to emotional influences. Pain-related brain potentials proved to be more sensitive for CPM effects than subjective ratings.

Normative data of contact heat evoked potentials from the lower extremities

Contact heat evoked potentials (CHEPs) have become an acknowledged research tool in the assessment of the integrity of the nociceptive system and gained importance in the diagnostic work-up of patients with suspected small fiber neuropathy. For the latter, normative values for CHEP amplitude and latency are indispensable for a clinically meaningful interpretation of the results gathered in patients. To this end, CHEPs were recorded in 100 healthy subjects over a wide age range (20–80 years) and from three different dermatomes of the lower extremities (L2, L5, and S2). A normal baseline (35–52 °C) and increased baseline stimulation (42–52 °C) were applied. Statistical analysis revealed significant effects of stimulation site, stimulation intensity, and sex on CHEP parameters (N2 latency, N2P2 amplitude, and NRS). Significant positive correlations of body height with N2 latency, and pain ratings with N2P2 amplitudes were observed. This is the first time that normative values have been obtained from multiple dermatomes of the lower extremities. The present dataset will facilitate the clinical application of CHEPs in the neurophysiological diagnosis of small fiber neuropathy and by discerning pathological findings help establish a proximal-distal gradient of nerve degeneration in polyneuropathies.

Contact heat evoked potentials: Reliable acquisition from lower extremities

ObjectiveTo investigate test-retest reliability of contact heat evoked potentials (CHEPs) from lower extremities using two different stimulation protocols, i.e., normal and increased baseline temperature. MethodsA total of 32 able-bodied subjects were included and a subset (N = 22) was retested. CHEPs were recorded from three different dermatomes of the lower extremity (i.e., L2, L5, and S2). Test-retest reliability of CHEPs acquisition after simulation in various lower limb dermatomes using different stimulation protocols was analyzed. ResultsThe study revealed an improved acquisition of CHEPS employing the increased baseline protocol, particularly when stimulating more distal sites, i.e., dermatome L5 and S2. Based on repeatability coefficients, CHEP latency (N2 potential) emerged as the most robust CHEP parameter. Although CHEP amplitudes (N2P2 complex) and pain ratings were decreased in the retest, amplitudes still showed fair to excellent intraclass correlation coefficients using normal baseline or increased baseline temperature, respectively. ConclusionsThis is the first study to demonstrate that CHEPs acquisition from the lower extremities is improved by increasing the baseline temperature of the thermode. SignificanceThis study highlights the usability of CHEPs as a viable diagnostic method to study small fiber integrity.

Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

Differences in contact heat-evoked potentials (CHEPs) between healthy subjects and patients with episodic or chronic migraine

Differences in contact heat-evoked potentials (CHEPs) between healthy subjects and patients with episodic or chronic migraine

Modulation of thermal somatosensory thresholds within local and remote spinal dermatomes following cervical repetitive magnetic stimulation

Background: Repetitive magnetic stimulation (rMS) modulates thermal somatosensory function at both low (0.2–1.0Hz) and high (5.0–20.0Hz) frequencies within the conditioned dermatome. However the effects of 1Hz and 20Hz cervical (C6-C7) rMS on thermosensory thresholds and contact heat evoked potentials (CHEPs) tested within local and remote spinal dermatomes are not known. Methods: Thirty healthy subjects participated in the study. Warm and cold detection threshold, heat and cold pain thresholds, and Cz/Fz CHEPs were evaluated within the C6, T10 and extrasegmental V3 control dermatome, before and after random assignment of subjects to sham, 1 or 20Hz C6-C7 rMS. Results: Following both 1 and 20Hz cervical rMS, warm detection threshold increased within the local C6 dermatome. Furthermore 1Hz cervical rMS increased warm detection threshold within the remote T10 dermatome, but not within the V3-trigeminal control area. Cervical rMS failed to modulate cold detection threshold, heat and cold pain threshold or Cz/Fz CHEP amplitude from the dermatomal test sites. Conclusion: Both 1 and 20Hz cervical rMS modulated warm detection threshold within the locally conditioned C6 dermatome. The concomitant increase in warm detection threshold within the T10 dermatome following 1Hz rMS provides evidence for remote neuromodulation of thermosensory function via intraspinal control mechanisms.

Differences in Spinothalamic Function of Cervical and Thoracic Dermatomes

After spinal cord injury, contact heat evoked potentials (CHEPs) may represent a means to refine the clinical assessment of sensory function from each spinal cord segment by quantifying nociception, including conduction along the spinothalamic tract. The influence of stimulation site (i.e., dermatomes) on CHEPs and thermal thresholds in 19 healthy subjects (mean age, 45.2 ± 18.3 years) divided into 2 age classes (younger subjects, n = 10; mean age, 28.8 ± 5.2 years; older subjects, n = 9; mean age, 63.4 ± 3.4 years) at 5 different dermatomes (C4, C5, C6, C8, and T4) was assessed. In terms of distance from the body midline (i.e., spinal cord entry), there was a reduction in CHEP amplitudes from proximal (C4 and T4) to distal (C6 and C8) dermatomes with a corresponding reduction in nociceptive perception (i.e., pain threshold and rating). Within primary and secondary cortical sensory areas, including areas associated with affective noxious processing, the cortical source density analysis showed a similar current density distribution between C4 and C8 dermatomes but consistent higher current densities for C4. The study supports CHEPs as a feasible tool for assessing discrete dermatomes corresponding to spinal cord segments. The results suggest that the proximodistal pattern in the intensity of perceived pain and CHEP amplitudes is likely attributable to the distribution of heat nociceptors and the increase in conduction distance from proximal to distal dermatomes. The present findings emphasize on the importance that if patients are assessed segment by segment, the underlying topographical differences need to be accounted for.

Differential Effects of a 5% lidocaine medicated patch in peripheral nerve injury

We examined the effect of topical lidocaine on the function of small and large fibers in patients with peripheral neuropathic pain due to traumatic or postoperative nerve injury. In an open-label study, 24 patients were treated with a 5% lidocaine patch for up to 12 weeks. We recorded contact heat evoked potentials (CHEPs) and performed quantitative sensory testing (QST) before and after treatment with the contralateral side as control. Twenty-one patients (mean age 47.6 ± 13.5 years) completed the study. Lidocaine increased cold pain threshold (P = 0.04) and reduced CHEP amplitude (P = 0.007) with no effect on other QST parameters. Patients responding to treatment had less cold detection deficit on the affected side and had a larger increase in cold pain detection threshold following treatment than nonresponders. Controlled trials are warranted to further understand the mechanisms mediating the effects of topical lidocaine.

Effects of Propofol, Sevoflurane, Remifentanil, and (S)-Ketamine in Subanesthetic Concentrations on Visceral and Somatosensory Pain–evoked Potentials

Although electroencephalographic parameters and auditory evoked potentials (AEP) reflect the hypnotic component of anesthesia, there is currently no specific and mechanism-based monitoring tool for anesthesia-induced blockade of nociceptive inputs. The aim of this study was to assess visceral pain-evoked potentials (VPEP) and contact heat-evoked potentials (CHEP) as electroencephalographic indicators of drug-induced changes of visceral and somatosensory pain. Additionally, AEP and electroencephalographic permutation entropy were used to evaluate sedative components of the applied drugs. In a study enrolling 60 volunteers, VPEP, CHEP (amplitude N2-P1), and AEP (latency Nb, amplitude Pa-Nb) were recorded without drug application and at two subanesthetic concentration levels of propofol, sevoflurane, remifentanil, or (s)-ketamine. Drug-induced changes of evoked potentials were analyzed. VPEP were generated by electric stimuli using bipolar electrodes positioned in the distal esophagus. For CHEP, heat pulses were given to the medial aspect of the right forearm using a CHEP stimulator. In addition to AEP, electroencephalographic permutation entropy was used to indicate level of sedation. With increasing concentrations of propofol, sevoflurane, remifentanil, and (s)-ketamine, VPEP and CHEP N2-P1 amplitudes decreased. AEP and electroencephalographic permutation entropy showed neither clinically relevant nor statistically significant suppression of cortical activity during drug application. Decreasing VPEP and CHEP amplitudes under subanesthetic concentrations of propofol, sevoflurane, remifentanil, and (s)-ketamine indicate suppressive drug effects. These effects seem to be specific for analgesia.

Neurophysiology and Intraoperative Nociception

Neurophysiology and Intraoperative Nociception

Effect of intrathecal baclofen on evoked pain perception: An evoked potentials and quantitative thermal testing study

Somatic antinociceptive effects of baclofen have been demonstrated in animal models. We hypothesized that if enhanced thermal or pain sensitivity is produced by loss of gamma-aminobutyric acid (GABA)-ergic tone in the central nervous system, spinal administration of GABA agonists might be predicted to be effective in thermal and/or pain perception changes and pain-related evoked potentials in candidates for intrathecal baclofen (ITB) treatment. Eleven patients with severe spinal cord injury (SCI) who suffered from severe spasticity were evaluated during a 50-μg ITB bolus test. Warm and heat pain thresholds, evoked heat pain perception, and contact heat-evoked potentials (CHEPs) were determined above SCI level from the right and left sides. Nine age- and gender-matched healthy volunteers undergoing repeat testing without any placebo injection served as control group. In patients, heat pain perception threshold increased, and evoked pain perception and amplitude of CHEPs decreased significantly after ITB bolus application in comparison with baseline (p < 0.005), with no change in warm perception threshold. In controls, no significant changes were observed in repeat testing over time. Our findings indicate that ITB modulates heat pain perception threshold, evoked heat pain perception and heat pain-related evoked potentials without inducing warm perception threshold changes in SCI patients. This phenomenon should be taken into account in the clinical evaluation and management of pain in patients receiving baclofen.

The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: An evoked potentials and quantitative thermal testing study

Neuropathic pain (NP) is common in spinal cord injury (SCI) patients. One of its manifestations is a lowering of pain perception threshold in quantitative thermal testing (QTT) in dermatomes rostral to the injury level. Transcranial direct current stimulation (tDCS) combined with visual illusion (VI) improves pain in SCI patients. We studied whether pain relief with tDCS + VI intervention is accompanied by a change in contact heat- evoked potentials (CHEPs) or in QTT. We examined 18 patients with SCI and NP before and after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and 14 healthy subjects served as controls. We assessed NP intensity using a numerical rating scale (NRS) and determined heat and pain thresholds with thermal probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated their perception of evoked pain using NRS during CHEPs. Thirteen patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI. Evoked pain perception was significantly higher than in the other two groups, and reduced significantly together with CHEPs amplitude after tDCS + VI with respect to baseline. Pain perception threshold was significantly lower than in the other two groups before tDCS + VI intervention, and increased significantly afterwards. Two weeks of tDCS + VI induced significant changes in CHEPs, evoked pain and heat pain threshold in SCI patients with NP. These neurophysiological tests might be objective biomarkers of treatment effects for NP in patients with SCI.

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. In the first study (psychophysical), 60 pregnant women underwent a quantitative sensory testing (QST) investigating heat perception in two body areas (right forearm and T10 dermatome) according to these groups: 32-33 gestational weeks (GW), 39-40 GW, early stage of active labour and 24 h after the delivery. In the other study (neurophysiological), contact heat-evoked potentials (CHEPs) were recorded in other 16 women at the 32nd GW and in 11 of these also at the 40th GW. The psychophysical study showed that heat pain threshold was significantly increased at the forearm at 32-33 GW (median ± IQR: 39.6 ± 0.7 °C), at 39-40 GW (40.6 ± 1.1 °C) and at early stage of active labour (40.8 ± 1.5 °C) as compared to 20 non-pregnant controls (p < 0.001). Heat pain threshold tested at T10 level was significantly increased at 32-33 GW (41.0 ± 1.6 °C), at 39-40 GW (42.1 ± 1.8 °C), and at early stage of active labour (42.3 ± 1.3 °C) as compared to the non-pregnant women (p < 0.001). The N2-P2 CHEP amplitude (main negative N2 and positive P2 components of the vertex biphasic potential) recorded from the pregnant women was significantly lower at the 40th than at the 32nd GW, after stimulation of both the forearm (p < 0.001) and the abdomen (p < 0.001). In pregnant women, there is a progressive increase of heat pain threshold and a reduction of the CHEP amplitude, suggesting that a general inhibitory mechanism may be involved.

Test–Retest Reliability of Contact Heat-Evoked Potentials From Cervical Dermatomes

The purpose of this study was to investigate the test-retest reliability of contact heat-evoked potentials (CHEPs) in neurologically healthy subjects from cervical dermatomes (C4-C8). Seventeen individuals underwent test-retest examination of cervical CHEPs. Peak latencies and peak-to-peak amplitude of N2-P2 and ratings of perceived intensity were analyzed using test-retest reliability statistics (intraclass correlation coefficients [ICCs] and Bland-Altman confidence parameters). For comparison, a group of similar age and gender was also examined with dermatomal somatosensory-evoked potentials (dSSEPs, n = 17). The ICC values for CHEP latency and amplitude parameters were significant (P < 0.05) and corresponded to at least "fair" reliability, while peak-to-peak amplitude demonstrated "substantial" (≥0.81) reliability for all dermatomes. The coefficients of repeatability (i.e., 2SD of the difference between examinations) confirm that CHEPs and dSSEPs are reliable according to measures of latency. Superior peak-to-peak amplitude test-retest reliability was found for CHEPs. In conclusion, the test-retest reliability of dSSEP and CHEP parameters supports the fact that these outcomes can be used to objectively track changes in spinal conduction in the dorsal column and spinothalamic tract, respectively. The reliable acquisition of CHEPs may depend on the intensity of the sensation reported by the subject for a given area of skin stimulated.

Increased baseline temperature improves the acquisition of contact heat evoked potentials after spinal cord injury

ObjectiveTo investigate the effect of increasing the skin surface baseline temperature for contact heat evoked potentials (CHEPs). MethodsCHEPs were studied in healthy subjects and subjects with chronic cervical spinal cord injury (SCI) using a conventional 35°C (condition 1) or increased 42–45°C baseline temperature (condition 2). A third condition was used to standardize the contact heat stimulus duration from the different baseline temperatures. Changes in peak latency and N2P2 amplitude of the CHEPs and rating of perceived intensity were examined between conditions. ResultsIn healthy subjects, increasing the baseline temperature for contact heat stimulation significantly increased the rating of perceived intensity (conditions 2 and 3), as well as the amplitude of CHEPs (condition 2 only). Following SCI, an increased baseline temperature facilitated perception of contact heat stimulation and evoked potentials could be recorded from dermatomes that were insensitive to contact heat from a conventional baseline temperature. ConclusionsEnhancing the acquisition of CHEPs can be achieved by increasing the baseline temperature. This effect can be attributed, in part, to shortening the stimulation duration. SignificanceAfter SCI, increasing the baseline temperature for CHEPs in dermatomes with absent or diminished sensation improved the neurophysiological resolution of afferent sparing.

A novel human volunteer pain model using contact heat evoked potentials (CHEP) following topical skin application of transient receptor potential agonists capsaicin, menthol and cinnamaldehyde

The discovery of transient receptor potential (TRP) receptors has advanced understanding of temperature sensation, and pre-clinical studies have identified TRP as major novel analgesic targets in inflammatory and neuropathic pain states. We systematically investigated the sensory effects and interactions of TRP agonists capsaicin (TRPV1), menthol (TRPM8) and cinnamaldehyde (TRPA1) applied topically to the skin in 14 healthy human participants. Capsaicin lowered heat pain thresholds while warm detection thresholds were unchanged, suggesting an effect purely on nociceptor nerve fibres. The amplitude of contact heat-evoked potentials (CHEP) and evoked pain ratings were negatively correlated after capsaicin, whereas CHEP had been correlated positively without capsaicin in a previous volunteer study. Menthol caused cold hypersensitivity and cinnamaldehyde caused heat hypersensitivity, but neither had an effect on evoked potentials. The CHEP after application of capsaicin show features observed in some patients with painful neuropathy, and could provide a model for development of novel analgesics, particularly TRPV1 antagonists.

On the relationship between nociceptive evoked potentials and intraepidermal nerve fiber density in painful sensory polyneuropathies

This study analyzed the relationship between the density of intraepidermal nerve fibers (IENF) and the characteristics of either nociceptive laser-evoked potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with painful sensory polyneuropathy with the aim to determine which parameters of LEPs and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy volunteers took part in the study. Based on clinical examination, nerve conduction tests, and quantitative sensory testing, we identified 52 patients with small-fiber neuropathy (SFN), 40 with mixed (small-fiber and large-fiber) neuropathy (MFN), and 4 who were excluded from the analysis because of no evidence of involvement of small fibers. The latency of the N2 was delayed for both LEPs and CHEPs in patients with MFN and for CHEPs only in patients with SFN. The amplitude of the vertex N2/P2 potential was similarly reduced in both types of neuropathy, but LEPs were more frequently absent than CHEPs in MFN patients (68% vs 40%). In general, latency and amplitude of LEPs and CHEPs were well correlated with IENF density. SFN patients were characterized by abnormal EPs and slightly decreased but morphologically abnormal IENF. MFN patients were characterized by frequently absent LEPs and CHEPs and a rather severe IENF loss.The correlation between nociceptive evoked potentials (laser-evoked potentials and contact heat-evoked potentials) and skin biopsy aids in the diagnosis of painful neuropathies.

Optimizing the Measurement of Contact Heat Evoked Potentials

Our aim was to determine whether single trial averaging could improve quantification of contact heat evoked potentials measured from fixed position contact heat stimulation. Event-related brain potentials were measured in response to contact heat stimuli applied to the arm and the leg of 10 subjects via a circular thermode, using fixed and varied thermode positions at 41 degrees C and 51 degrees C. Contact heat evoked potentials were successfully recorded from varied position stimulation of the leg at 51 degrees C in 80% of subjects, but from only 60% of subjects using a fixed position. Contact heat evoked potentials were only identified in a small number of subjects when stimulating at 41 degrees C. The amplitude of the N2-P2 complex and pain intensity ratings were larger for the varied compared with the fixed thermode position and were also larger when stimulating the arm. Automated single trial analysis of the data resulted in larger amplitude of the N2-P2 complex than standard averaging. In conclusion, we have demonstrated that the reduced contact heat evoked potentials amplitude seen for fixed location stimulation can be improved with single-trial averaging.

Small fibre function in patients with meralgia paresthetica

Introduction: Patients with meralgia paresthetica (MP) usually experience not only paraesthesias and decreased tactile sensation, but also painful dysesthesias in the distribution of the lateral femoral cutaneous nerve (LFCN). We aimed at assessing whether there is any functional impairment of small fibres of the LFCN in patients with MP. Methods: We carried out a clinical, psychophysical and neurophysiological study in 14 patients with MP and 14 healthy control subjects. We assessed pain in the last 2 months, thermal thresholds and small fibres conduction by using a visual analogue scale (VAS-pain), quantitative sensory testing (QST) and contact heat-evoked potentials (CHEPs), respectively. Data were grouped for control subjects, non-affected side and affected side of patients with MP. Results: Patients marked a VAS-pain of 4.3 ± 1.5. In the affected side, thresholds for warm and heat pain sensations were elevated and the amplitude of CHEPs was reduced in comparison to the non-affected side and controls (Bonferroni’s test; p < 0.001 for all comparisons). The amplitude of CHEPs correlated inversely with duration of the symptoms ( r = −0.57, p = 0.002), as well as with heat pain thresholds ( r = −0.18, p = 0.01). No significant correlations were found between CHEPs and VAS-pain ( p > 0.05 for all correlations). Conclusion: Besides the involvement of large myelinated fibres, partial loss of function in small fibres may also account for the painful symptoms of patients with MP, especially in those with longer disease duration.