Central pain: clinical and physiological characteristics.

OBJECTIVES--To study the clinical and pathophysiological features of central pain due to damage to the CNS. METHODS--156 patients (mostly with ischaemic strokes, some with infarct after subarachnoid haemorrhage and other cerebral conditions; one with bulbar and others with spinal pathology) with central pain have been investigated clinically and varying numbers instrumentally with respect to quantitative somatosensory perception thresholds and autonomic function. RESULTS--Pain onset was immediate in a minority; and from a week or two up to six years in > 60%. For those with supraspinal ischaemic lesions, the median age of onset was 59; dominant and non-dominant sides were equally affected. Two thirds of the patients had allodynia, including a previously undescribed movement allodynia apparently triggered from group I afferents. Most patients exhibited autonomic instability in that their pain was increased by physical and emotional stress and alleviated by relaxation; cutaneous blood flow and sweating may also be affected. Pain occurred within a larger area of differential sensory deficit. The critical deficit seems to be for thermal and pinprick sensations, which were more pronounced in areas of greatest than in areas of least pain; whereas low threshold mechanoceptive functions, if affected, did not vary between areas of greatest and least pain. Skinfold pinch (tissue damage) pain thresholds were only slightly affected in supraspinal cases, but greatly increased in patients with spinal lesions; thermal (heat) pain did not show this dissociation. CONCLUSION--The pathogenetic hypothesis which seems best to fit the findings is that there is up regulation or down regulation of receptors for transmitters, possibly mainly noradrenergic, over time.     

Central post-stroke pain in Wallenberg syndrome]

We analyzed clinical characteristics of central post-stroke pain (CPSP), constant and burning pain, in 32 patients with Wallenberg syndrome due to infarction. CPSP developed in 44% (14/32) of the patients; 8 in acute stage (within 4 days after the stroke) and 8 in chronic stage(10-120 days after the stroke). Apart from one exceptional case, CPSP was present in the hypalgesic side of face and extremities. In 9 cases of typical type (Currier's distribution of sensory disturbance), CPSP occurred in the ipsilateral face to the lesion during acute stage. Among them, 2 cases developed severe lancinating pain in chronic stage. In 5 cases of ventral type, it occurred in the contralateral extremities during chronic stage. Spino- and trigemino-thalamic tract are injured but medullary reticular formation is intact in Wallenberg syndrome. It is, therefore, considered that CPSP in Wallenberg syndrome is caused by denervation sensitivity of "paleo-reticulothalamic" tract within the reticular formation.     

Central post-stroke pain or paresthesia in lenticulocapsular hemorrhages

Twenty patients were studied who developed central poststroke pain or paresthesia after lenticulocapsular hemorrhage. Pain or paresthesia occurred 0 to 24 months after the onset, more prominently in the leg than other body parts. The symptoms were described as numb, cold, burning, aching, swollen, and squeezing in various combinations. The mean score of the visual numerical scale was 5.6. The lesions involved the dorsal part of the posterior limb of the internal capsule, probably damaging the thalamocortical sensory pathway.     

Postherpetic neuralgia: epidemiology, pathophysiology and management

Postherpetic neuralgia (PHN) is a neuropathic pain syndrome and is the most common complication of herpes zoster (HZ; shingles). PHN occurs mainly in HZ patients 60 years of age and older, in particular in those suffering from more severe acute pain and rash. Administration of antiviral drugs reduces the duration of pain associated with HZ. The pathophysiology of PHN may be distinctly different between patients with either reduced or increased skin sensitivity. Therapy is with tricyclic drugs (e.g., nortriptyline), alpha 2 delta-ligands (e.g., gabapentin) or opiates with adjunctive topical lidocaine or capsaicin. Mechanism-based therapy is a desirable goal but so far proves elusive. The incidence of HZ, and therefore that of PHN, is likely to increase as a result of greater longevity and increasing numbers of patients receiving treatment that compromises cell-mediated immunity. A zoster vaccine for administration to adults reduces the incidence of HZ and PHN, as well as the burden of illness associated with these conditions.     

Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management

Patients with the nephrotic syndrome are at increased risk of developing venous and arterial thromboembolism, the most common of which is renal vein thrombosis. There are several unanswered or controversial issues relating to the nephrotic syndrome and thromboembolism, which include the mechanism of thromboembolism, and optimal diagnostic and anticoagulant management strategies. This review will discuss several of these issues: the epidemiology and clinical spectrum of thromboembolic disease occurring in patients with the nephrotic syndrome; the pathophysiology of the hypercoagulable state associated with the nephrotic syndrome; the diagnosis of renal vein thrombosis in the nephrotic syndrome; and the evidence for prophylactic and therapeutic anticoagulation strategies in such patients.     

Neurogenic hypertension: pathophysiology,diagnosis and management

Clinical Autonomic Research - Discussions about the cause and treatment of essential hypertension usually focus on mechanisms such as sodium/volume and the renin–angiotensin system. Less...     

An East-West approach to the management of central post-stroke pain

The development of neuropathic pain following stroke is not uncommon. The consequences include significant disabilities and depression. Treatment can often be difficult and responses unsatisfactory. We report a patient with severe central post-stroke pain (CPSP) of the right leg benefiting from a combination of Western multidisciplinary therapies AND acupuncture. A literature search has revealed that relatively few studies have been done on the management of CPSP, compared with other types of neuropathic pain. Amitriptyline and carbamazepine were found to produce positive effects on post-stroke pain in one small study; lamotrigine and gabapentin are two newer drugs which appear promising. To the best of our knowledge, the use of acupuncture for the treatment of CPSP has not been previously reported.     

Towards a mechanism-based view on post-stroke shoulder pain: theoretical considerations and clinical implications

The assessment and treatment of post-stroke shoulder pain (PSSP) is largely based on the assumption that pain is due to biomechanical alterations within the shoulder joint after stroke. However, current treatment often provides limited pain relief, leading to a considerable number of patients with persistent pain. This suggests that PSSP may not be merely due to simple nociception from the shoulder joint. A better understanding of the neurophysiological mechanisms underlying the development and perpetuation of PSSP is needed. Here, a theoretical framework for presumed PSSP mechanisms and their assessment is presented based on key concepts applied in pain research. This theoretical framework assumes that although pain may be localized in one region of the body, the mechanisms causing pain may occur at any level of the somatosensory neuro-axis. Detailed assessment of pain complaints and somatosensory abnormalities should, therefore, be a key element in clinical PSSP research. Studies aiming to further characterize somatosensory functions in patients with PSSP (initially) need to take a broad methodological approach including both clinical as well as more experimental pain research tools, such as quantitative sensory testing. A better understanding of pain mechanisms may explain why persistent PSSP and unsatisfactory pain relief are common despite active prevention and treatment strategies and may provide a basis for improved clinical management of PSSP.     

Trochlear pain: clinical characteristics and treatment outcomes

Trochlear pain is frequently overlooked as published data regarding the clinical characteristic and current treatment are limited. The aim of this study is to evaluate this information from our experiences with trochlear pain. Medical records of 43 patients with trochlear pain from HRH Princess Maha Chakri Sirindhorn Medical Center between November 2010 and April 2017 were reviewed. Most patients were female (88%), with a median age of 51 years. Common characteristic symptoms of trochlear pain were acute, episodic, dull or pressure-like, periorbital pain, often radiating to the forehead, and aggravated by eye movements, especially reading. The causes of trochlear pain were idiopathic or primary trochlear headache (n = 33, 77%) and trochleitis (n = 10, 23%). Treatments included oral NSAIDs or dexamethasone injection into the trochlear region. At a median follow-up of 11 months (range 0–64), 67% of the patients reported complete remission using oral medication. Local steroid injection is useful in non-responding patients to oral therapy with an overall remission of 86%. Successful treatment outcome was achieved in most patients.     

脑血管病后癫痫的临床特征及危险因素分析

目的探讨脑血管病后癫痫(PSE)的临床特点及相关危险因素。方法分析528例脑血管病患者的临床特征,随访癫痫发作的情况,包括发作时间、发作类型、病变部位及预后等,通过单因素及多因素统计分析PSE发作的相关危险因素。结果 PSE与性别、年龄、高血压史、糖尿病史、冠心病史、房颤、吸烟史等因素无明显相关性,而与既往卒中病史、累及皮质、多脑叶病灶呈相关性。结论既往患者有卒中病史、脑出血患者以及病灶累及多脑叶、皮质者更容易继发癫痫。     

Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management

Neurogenic orthostatic hypotension is a distinctive and treatable sign of cardiovascular autonomic dysfunction. It is caused by failure of noradrenergic neurotransmission that is associated with a range of primary or secondary autonomic disorders, including pure autonomic failure, Parkinson’s disease with autonomic failure, multiple system atrophy as well as diabetic and nondiabetic autonomic neuropathies. Neurogenic orthostatic hypotension is commonly accompanied by autonomic dysregulation involving other organ systems such as the bowel and the bladder. In the present review, we provide an overview of the clinical presentation, pathophysiology, epidemiology, evaluation and management of neurogenic orthostatic hypotension focusing on neurodegenerative disorders.     

Malignant bone pain: pathophysiology and treatments

Metastatic involvement of the bone is one of the most frequent causes of pain in cancer patients and represents one of the first signs of widespread neoplastic disease. The pain may originate directly from the bone, from nerve root compression, or from muscle spasms in the area of the lesions. The mechanism of metastatic bone pain is mainly somatic (nociceptive), even though, in some cases, neuropathic and visceral stimulations may overlap. The conventional symptomatic treatment of metastatic bone pain requires the use of multidisciplinary therapies, such as radiotherapy, in association with systemic treatment (hormonotherapy, chemotherapy, radioisotopes) with the support of analgesic therapy. Recently, studies have indicated the use of bisphosphonates in the treatment of pain and in the prevention of skeletal complications in patients with metastatic bone disease. In some patients, pharmacologic treatment, radiotherapy, and radioisotopes administered alone or in association are not able to manage pain adequately. The role of neuroinvasive techniques in treating metastatic bone pain is debated. The clinical conditions of the patient, his life expectancy, and quality of life must guide the physician in the choice of the best possible therapy.     

Endothelin-1-induced pain and hyperalgesia: a review of pathophysiology, clinical manifestations and future therapeutic options

Pain in patients with metastatic cancer contributes to increased suffering in those already burdened by their advancing illness. The causes of this pain are unknown, but are likely to involve the action of tumour-associated mediators and their receptors. In recent years, several chemical mediators have increasingly come to the forefront in the pathophysiology of cancer pain. One such mediator, endothelin-1 (ET-1), is a peptide of 21 amino acids that was initially shown to be a potent vasoconstrictor. Extensive research has revealed that members of the ET family are indeed produced by several epithelial cancerous tumours, in which they act as autocrine and/or paracrine growth factors. Several preclinical and clinical studies of various malignancies have suggested that the ET axis may represent an interesting contributor to tumour progression. In addition, evidence is accumulating to suggest that ET-1 may contribute to pain states both in humans and in other animals. ET-1 both stimulates nociceptors and sensitises them to painful stimuli. Selective stimulation of ET receptors has been implicated as a cause of inflammatory, neuropathic and tumoural pain. ET-1-induced pain-related behaviour seems to be mediated either solely by one receptor type or via both endothelin-A receptors (ETAR) and endothelin-B receptors (ETBR). Whereas stimulation of ETAR on nociceptors always elicits a pain response, stimulation of ETBR may cause analgesia or elicit a pain response, depending on the conditions. The administration of ETAR antagonists in the receptive fields of these nociceptors has been shown to ameliorate pain-related behaviours in animals, as well as in some patients with advanced metastatic prostate cancer. The identification of tumour-associated mediators that might directly or indirectly cause pain in patients with metastatic disease, such as ET-1, should lead to improved, targeted analgesia for patients with advanced cancer. In this review, we will describe the current status of the role of ET-1 in different types of painful syndromes, with special emphasis on its role in the pathophysiology of cancer pain. Finally, potential new treatment options that are based on the role of the ET axis in the pathophysiology of cancer are elaborated.     

Welding-related parkinsonism: clinical features, treatment, and pathophysiology

OBJECTIVE: To determine whether welding-related parkinsonism differs from idiopathic PD. BACKGROUND: Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder. METHODS: The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations. RESULTS: Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen. CONCLUSIONS: Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.     

Hypnic headache: clinical features,pathophysiology, and treatment

Hypnic headache has been described in several case reports since 1981 and is regarded as an idiopathic headache disorder. In this review of 71 cases in the literature, the clinical features, neurophysiologic including polysomnographic findings, and treatment procedures are analyzed and the pathophysiology of this condition, which remains however speculative, is discussed. There is some evidence that hypnic headache is related to REM sleep. The analysis shows that hypnic headache most probably is an entity among the idiopathic headache disorders unassociated with structural lesions and does not belong to the trigeminal-autonomic cephalalgias. Lithium shows the best efficacy; indomethacin, flunarizine, and caffeine may also be useful.