[Trigeminal neuralgia: drug therapy : The new German guideline]. / Medikamentöse Therapie der Trigeminusneuralgie : Die neue Leitlinie.

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.

Sensory Profiles in Patients with Low Back Pain with and Without Radiculopathy.

OBJECTIVE: During routine clinical evaluation, it can be challenging to differentiate between lumbar radiculopathy (RAD) and lower back pain with non-radicular somatic referred pain (SRP) or even axial non-radiating low back pain (LBP). The aim of this study was to characterize patients with RAD, axial LBP (aLBP), and SRP on the basis of somatosensory profiles. METHODS: Patients with LBP (n = 54) were assessed with quantitative sensory testing in the area of LBP and, in cases of RAD, additionally in the area of projecting pain. Questionnaires (PainDETECT®, EuroQol-5D, Medical Outcomes Study Sleep Scale, Hannover Functional Ability Questionnaire for Back Pain, Roland Morris Disability Questionnaire, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale) were answered by all patients. RESULTS: Patients with RAD (n = 12) had higher pain intensity scores (numeric rating scale: 5.7 ± 1.5 vs 4.1 ± 2.2; P < 0.05) and higher PainDETECT scores (14.6 ± 6.13 vs 9.7 ± 6.2; P < 0.05) than did patients with aLBP and SRP (n = 42). Patients with RAD had a more pronounced loss of small-fiber function, increased mechanical hyperalgesia, and a trend toward increased sensitivity to thermal pain in the area of LBP compared with patients with aLBP and SRP. Within patients with RAD, sensory profiles of the area of projecting pain and the area of LBP did not differ. Pressure pain hyperalgesia (measured by pressure pain threshold) and loss of mechanical detection (measured by mechanical detection threshold) in combination with the PainDETECT items numbness and prickling reached the best predictive value in detecting a radiculopathy. CONCLUSIONS: Patients with RAD demonstrated more somatosensory abnormalities than did patients with aLBP and SRP, including increased mechanical hyperalgesia and a loss of mechanical detection. The combination of pressure pain threshold, mechanical detection threshold, numbness, and prickling in the area of LBP can be a time-efficient tool to identify patients with RAD.

Do doctors treat themselves differently than their patients? Study on the self-treatment of migraine among German neurologists and pain specialists.

AIM: To investigate whether the self-treatment of migraine among neurologists and pain specialists corresponds to national medical guidelines and treatment of patients. METHODS: An email cross-sectional survey was sent to members of the German Society for Neurology, German Pain Society and German Migraine and Headache Society containing questions on demographics, professional experience and specialization and - in case participants suffered from migraine - questions about their migraine and its treatment. RESULTS: 175/418 (41.9%) participants suffered from migraine (m: 29.3%; f: 55.2%, 45.9 ± 10.7 years). For acute migraine attacks, 96.6 % of them use a first-line treatment according to the medical guidelines. Seventeen (9.7%) are currently taking a migraine prophylaxis, 52.9% of these use a recommended first-line prophylaxis. In all, 21.7% are not taking a prophylactic treatment despite an indication (based on number of monthly migraine days) for it, due to fear of side-effects, low intensity of migraine attacks and a sufficient effect of acute medication. This group of participants was younger, less experienced and specialized and was mainly employed (vs. self-employed) compared to those taking a prophylaxis. A total of 96.6% reported treating their patients in line with current guidelines; 14.3% would treat themselves differently when they were their own patients. CONCLUSION: The self-treatment of acute migraine attacks for the most part complies with the guidelines but, regarding the indication for a prophylaxis, a more divergent treatment approach was observed among younger, less experienced physicians. For the majority of physicians there is no difference between self-treatment and treatment of migraine patients.

Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-study.

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

[Syncopes]. / Synkopen.

Syncopes are defined as sudden and short unconsciousness with loss of muscular tonus which are reversible without further intervention. Differentiation from other short-lasting changes of consciousness as in seizures, blood flow abnormalities of brainstem, metabolic disorders, intoxication or traumatic loss of consciousness is important for further diagnostic and adequate treatment.

Should you stop wearing neckties?-wearing a tight necktie reduces cerebral blood flow.

PURPOSE: Negative cerebrovascular effects can be expected by compressing jugular veins and carotids by a necktie. It was already demonstrated that a necktie increases intraocular pressure. In many professions, a special dress code including a necktie and a collared shirt is mandatory although little is known about the effect of this "socially desirable strangulation." METHODS: In this study, the effect of wearing a necktie concerning cerebral blood flow and jugular venous flow by magnetic resonance imaging. Thirty volunteers were divided in two groups. One underwent MRI with necktie, the other without. RESULTS: The examination resulted in a statistically significant decrease of CBF after tightening the necktie (p < 0.001) while the venous flow did not show any significant changes. CONCLUSION: It appears that wearing a necktie leads to a reduction in CBF.

Stratification of neuropathic pain patients: the road to mechanism-based therapy?

PURPOSE OF REVIEW: It has been demonstrated that within one pain entity, patients may report highly heterogenic sensory signs and symptoms. Although mechanism might differ fundamentally between those patients, yet the treatment recommendations are uniform throughout all phenotypes. Therefore, the introduction of new stratification tools could pave the way to an individualized pain treatment. RECENT FINDINGS: In the past, retrospective stratifications of patients successfully identified responders to certain pharmacological treatments. This indicated predictive validity and reliability of this classification tool in those patient subgroups. Further on, these observations have been confirmed in prospective studies. SUMMARY: This review focusses on recent achievements in neuropathic pain and suggests a promising implementation of an individualized pharmacological therapy in the future.

Clinical Manifestation of Acute, Subacute, and Chronic Low Back Pain in Different Age Groups: Low Back Pain in 35,446 Patients.

BACKGROUND: Low back pain (LBP) is a major healthcare problem causing tremendous economic costs. METHODS: Clinical manifestation of LBP was characterized in 35,446 patients. We focused on the comparison of the acute, subacute, and chronic LBP stage with regard to patients' ages, based on epidemiologic and clinical questionnaires (eg, painDETECT Questionnaire, Pain Disability Index), pain intensity, pain descriptors, and functional impairment. RESULTS: We found that neuropathic components were most frequent in chronic LBP patients at the ages of 51 to 60 years. Elderly LBP patients showed a decrease in neuropathic and an increase in nociceptive pain. The most frequently reported pain descriptors were "pressure pain" and "pain attacks" through all stages of LBP, whereas "burning" and "prickling" were most frequent in the chronic stage. Patients after back surgery presented neuropathic pain symptoms most frequently and had the highest amount of pain medication intake. CONCLUSIONS: Burning and prickling were revealed as possible indicators for LBP chronicity. Combined with pain attacks and pressure pain, these 4 pain descriptors might be a promising adjunct to pain intensity in terms of outcome parameters for future LBP studies. The decrease of neuropathic pain syndromes in the elderly might be explained by degenerative processes. The presented work provides important insights on LBP management in the acute, subacute, and chronic stages.

A-Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin-Induced Neuropathy.

Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin-induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A-fiber afferents in combination with quantitative sensory testing. Additionally, an interview-based questionnaire assessed the severity of symptoms and the impact on daily activities. Results indicate a deficit of cold perception in patients without cold hyperalgesia compared to patients with cold hyperalgesia prior to A-fiber blockade. In patients with cold hyperalgesia, a preferential blockade of A-fibers abolished cold hyperalgesia. This suggests that oxaliplatin-induced cold hyperalgesia is mediated by A-fibers and that a deficit in A-fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A-fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin-induced cold hyperalgesia.

Neuropathic Pain.

Diagnosing neuropathic pain and distinguishing it from nociceptive pain can be challenging, but is essential because both forms of pain require different treatment strategies. The diagnosis of neuropathic pain is primarily based on clinical findings. Therefore, a careful, focused history and an examination of the signs characteristic of neuropathic pain are crucial. Imaging techniques and electrophysiological examinations, as well as punch skin biopsy can support the clinical diagnosis. Ideally, treatment should be individualized using a mechanism-based approach. However, current treatments are usually dispensed without precision, and calcium-channel-acting modulators (pregabalin, gabapentin), tricyclic antidepressants, and serotonin-noradrenalin reuptake inhibitors (duloxetine, venlafaxine) represent first-line treatment options for neuropathic pain. Although neurostimulation techniques for the treatment of refractory chronic pain have become more important, most evidence of long-term effectiveness and safety is still limited, which strengthens the need for larger randomized controlled trials before final recommendations can be made.

Spinal and supraspinal processing of thermal stimuli: an fMRI study.

PURPOSE: To assess and characterize responses to innocuous/noxious thermal stimuli and heat allodynia using functional spinal magnetic resonance imaging (spinal fMRI). MATERIALS AND METHODS: Spinal/supraspinal activation patterns of 16 healthy subjects were investigated by applying painful and nonpainful heat stimuli to dermatome C6 baseline and after sensitization with the heat/capsaicin model using fMRI (3T, single-shot TSE, TR 9000 msec, TE 38 msec, FOV 288 × 144 × 20 mm, matrix 192 × 96, voxel size 1 × 1 × 2 mm). RESULTS: Increased activity was observed in ipsi- and contralateral ventral and dorsal spinal horn during noxious heat and heat allodynia. During noxious heat, but not during heat allodynia, activations were visible in the periaqueductal gray, ipsilateral cuneiform nucleus, and ipsilateral dorsolateral pontine tegmentum (DLPT). However, during heat allodynia activations were observed in bilateral ruber nuclei, contralateral DLPT, and rostral ventromedial medulla oblongata (RVM). Activations in contralateral subnucleus reticularis dorsalis (SRD) were visible during both noxious heat and heat allodynia (T >2.5, P < 0.01 for all of the above). After sensitization, activations in RVM and SRD correlated with activations in the ipsilateral dorsal horn of the spinal cord (R = 0.52-0.98, P < 0.05). CONCLUSION: Spinal fMRI successfully demonstrates increased spinal activity and secondary changes in activation of supraspinal centers involved in pain modulation caused by peripheral nociceptor sensitization. J. Magn. Reson. Imaging 2015;41:1046-1055. © 2014 Wiley Periodicals, Inc.

Bilateral hypersensitivity to capsaicin, thermal, and mechanical stimuli in unilateral complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome is multifactorial. Exaggerated inflammatory responses to limb injury may be involved. The authors hypothesized that capsaicin-induced pain and neurogenic inflammation (skin perfusion and flare area) are increased in patients with complex regional pain syndrome compared with that in controls. METHODS: Twenty patients with unilateral upper-limb complex regional pain syndrome and 20 age-, sex-, and body mass index-matched controls participated. Topical capsaicin 5% was applied to the back of both hands for 30 min, and pain intensity was assessed on a visual analogue scale. A laser Doppler perfusion imager scanner estimated capsaicin-induced skin perfusion and flare area. Autonomic and small-fiber function was assessed by sensory testing, quantitative sudomotor axon reflex test, and vasoconstrictor responses. RESULTS: The authors found bilateral hypersensitivity to capsaicin (P ≤ 0.02), skin fold (P = 0.001), joint pressure (P < 0.0001), cold (P ≤ 0.01), and heat pain (P ≤ 0.04) in patients compared with that in controls and thermal and mechanical hyperalgesia in the complex regional pain syndrome-affected hand compared with that in the unaffected hand (P ≤ 0.001). The patients had normal capsaicin-induced flare areas, thermal detection thresholds, quantitative sudomotor axon reflex test, and vasoconstrictor responses. CONCLUSIONS: The main finding is bilaterally increased capsaicin-induced pain in patients compared with controls. The flare response to capsaicin was normal, suggesting that the increased pain response was not due to increased neurogenic inflammation. The bilateral hypersensitivity to painful chemical, thermal, and mechanical stimuli not confined to the innervation area of a peripheral nerve or root cannot be explained by a regional change and may partly be due to central sensitization.

Pupillometry as a Potential Objective Measurement of Pain Assessment in Healthy Volunteers.

Background: Pain leads to activation of the autonomic nervous system and thus, among other things, to pupillary reflex dilation (PRD). Previous studies have already confirmed a correlation between the perception of pain and the pupillary reaction, measured using pupillometry. However, the previous study populations were under the influence of medication for analgesia in perioperative setting or suffered from pain. This study examines the relationship between pupillary reaction and pain perception in healthy controls and addresses the question of whether endogenous pain inhibition, clinically tested by conditioned pain modulation (CPM), can be quantified using pupillometry. Methods: Forty-two healthy volunteers (21 females, 21 males, mean age 27.9 ± 5.8 years, range 20-39 years) were included in this study. The PRD, as a measure of the pupillary reaction (variance from the base diameter in percent), was investigated during baseline, heat application and during CPM testing and results compared to the reported pain intensity on the numerical rating scale (NRS). Results: The volunteers showed higher variances under painful conditions compared to the measurement at rest corresponding to higher sympathetic activity during pain. Volunteers with a higher variance, ie a stronger pupillary reaction, gave higher pain ratings than subjects with a lower pupil variance. However, there was no correlation between the NRS and PRD. PRD and pain ratings during CPM were significantly lower compared to heat pain application alone. However, there was no correlation between the calculated CPM effect and the PRD. Conclusion: Pupillometry is capable of objectively reflecting the pain response, eg pain relief through CPM testing. However, the CPM effect calculated from the subjective pain ratings and the objective PRD measurements is not associated suggesting that both measure different aspects of pain perception. It must be discussed whether the CPM effect can be the correct measure for the functionality of the pain system.

The role of cytokines and chemokines in the maintenance of chronic pain-a pilot study.

Introduction: The immune system is believed to be important in the initiation and maintenance of chronic pain. Objectives: The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls. Methods: Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41-92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings. Results: Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL, P < 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL, P < 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL, P = 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL, P < 0.01), whereas no differences were observed in serum. Conclusion: Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.

Cold-evoked potentials in Fabry disease and polyneuropathy.

Background: Fabry disease (FD) causes cold-evoked pain and impaired cold perception through small fiber damage, which also occurs in polyneuropathies (PNP) of other origins. The integrity of thinly myelinated fibers and the spinothalamic tract is assessable by cold-evoked potentials (CEPs). In this study, we aimed to assess the clinical value of CEP by investigating its associations with pain, autonomic measures, sensory loss, and neuropathic signs. Methods: CEPs were examined at the hand and foot dorsum of patients with FD (n = 16) and PNP (n = 21) and healthy controls (n = 23). Sensory phenotyping was performed using quantitative sensory testing (QST). The painDETECT questionnaire (PDQ), FabryScan, and measures for the autonomic nervous system were applied. Group comparisons and correlation analyses were performed. Results: CEPs of 87.5% of the FD and 85.7% of the PNP patients were eligible for statistical analysis. In all patients combined, CEP data correlated significantly with cold detection loss, PDQ items, pain, and autonomic measures. Abnormal CEP latency in FD patients was associated with an abnormal heart frequency variability item (r = -0.684; adjusted p = 0.04). In PNP patients, CEP latency correlated significantly with PDQ items, and CEP amplitude correlated with autonomic measures (r = 0.688, adjusted p = 0.008; r = 0.619, adjusted p = 0.024). Furthermore, mechanical pain thresholds differed significantly between FD (gain range) and PNP patients (loss range) (p = 0.01). Conclusions: Abnormal CEPs were associated with current pain, neuropathic signs and symptoms, and an abnormal function of the autonomic nervous system. The latter has not been mirrored by QST parameters. Therefore, CEPs appear to deliver a wider spectrum of information on the sensory nervous system than QST alone.

What is associated with painful polyneuropathy? A cross-sectional analysis of symptoms and signs in patients with painful and painless polyneuropathy.

ABSTRACT: It is still unclear how and why some patients develop painful and others painless polyneuropathy. The aim of this study was to identify multiple factors associated with painful polyneuropathies (NeuP). A total of 1181 patients of the multicenter DOLORISK database with painful (probable or definite NeuP) or painless (unlikely NeuP) probable or confirmed neuropathy were investigated clinically, with questionnaires and quantitative sensory testing. Multivariate logistic regression including all variables (demographics, medical history, psychological symptoms, personality items, pain-related worrying, life-style factors, as well as results from clinical examination and quantitative sensory testing) and machine learning was used for the identification of predictors and final risk prediction of painful neuropathy. Multivariate logistic regression demonstrated that severity and idiopathic etiology of neuropathy, presence of chronic pain in family, Patient-Reported Outcomes Measurement Information System Fatigue and Depression T-Score, as well as Pain Catastrophizing Scale total score are the most important features associated with the presence of pain in neuropathy. Machine learning (random forest) identified the same variables. Multivariate logistic regression archived an accuracy above 78%, random forest of 76%; thus, almost 4 out of 5 subjects can be classified correctly. This multicenter analysis shows that pain-related worrying, emotional well-being, and clinical phenotype are factors associated with painful (vs painless) neuropathy. Results may help in the future to identify patients at risk of developing painful neuropathy and identify consequences of pain in longitudinal studies.

Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort.

ABSTRACT: We aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10-8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the "irritable" nociceptor profile to those with a "nonirritable" nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10-8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.

The pandemic's effect on a patient cohort with painful polyneuropathy in 2020: A longitudinal study on pain, mood, and everyday life.

In the early phase of the COVID pandemic 2020, we demonstrated how patients with painful polyneuropathy, against our expectations, did not experience a deterioration of their neuropathic pain. We hypothesized that our assessed measures, that is, pain intensity and characteristics, emotional wellbeing, and everyday life, would deteriorate in the further course of the pandemic according to the phases of disaster management. Thus, the aim of our study was to investigate patients repeatedly under varying pandemic conditions from March until December 2020. Sixty-three patients were investigated with validated questionnaires (brief pain inventory [BPI], neuropathic pain symptom inventory [NPSI], pain catastrophizing scale [PCS], patient-reported outcomes measurement information system [PROMIS] pain interference/sleep disturbance/fatigue/ depression/anxiety, EuroQol 5 dimensions 5 level version [EQ-5D-5L]) and a pandemic-specific, self-designed questionnaire. The data from the beginning of the pandemic with severe restrictions, during summer with loosened regulations and from December 2020 with reinstalled, severe restrictions were compared with an observational design. Patients reported higher pain severity when restrictions were lower. Sleep, mood, and quality of life did not change in the course of the pandemic in the validated measures. Pain interference significantly decreased during the study independent from restrictions. Patients who reported medical disadvantages had a lower quality of life upon EuroQol 5 dimension (EQ-5D) and were significantly more worried about their health. The perception of pain intensity was dependent on pandemic severity. Sleep, mood, and quality of life did not change significantly in validated measures. Continued medical care seems decisive to prevent worsening of pain and quality of life.