Persistent headache and low back pain after accidental dural puncture in the obstetric population: a prospective, observational, multicentre cohort study.

Accidental dural puncture following epidural insertion can cause a post-dural headache that is defined by the International Headache Society as self-limiting. We aimed to confirm if accidental dural puncture could be associated with persistent headache and back pain when compared with matched control parturients. We performed a prospective multicentre cohort study evaluating the incidence of persistent headache following accidental dural puncture at nine UK obstetric units. Parturients who sustained an accidental dural puncture were matched with controls who had undergone an uneventful epidural insertion. Participants were followed-up at six-monthly intervals for 18 months. Primary outcome was the incidence of persistent headache at 18 months. Ninety parturients who had an accidental dural puncture were matched with 180 controls. The complete dataset for primary analysis was available for 256 (95%) participants. Incidence of persistent headache at 18 months was 58.4% (52/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 18.4 (6.0-56.7), p < 0.001, after adjustment for past history of headache, Hospital Anxiety and Depression Scale (depression) and Hospital Anxiety and Depression Scale (anxiety) scores. Incidence of low back pain at 18 months was 48.3% (43/89) in the accidental puncture group and 17.4% (29/167) in the control group, odds ratio (95%CI) 4.14 (2.11-8.13), with adjustment. We have demonstrated that accidental dural puncture is associated with long-term morbidity including persistent headache in parturients. This challenges the current definition of post-dural puncture headache as a self-limiting condition and raises possible clinical, financial and medicolegal consequences.

European Academy of Neurology guideline on trigeminal neuralgia.

BACKGROUND AND PURPOSE: Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN. METHODS: A systematic review of the literature was performed and recommendations was developed based on GRADE, where feasible; if not, a good practice statement was given. RESULTS: The use of the most recent classification system is recommended, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. Magnetic resonance imaging (MRI), using a combination of three high-resolution sequences, should be performed as part of the work-up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long-term treatment, carbamazepine or oxcarbazepine are recommended as drugs of first choice. Lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add-on therapy. It is recommended that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first-line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, it is recommended that patients are offered psychological and nursing support. CONCLUSIONS: Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management.

EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.

BACKGROUND AND OBJECTIVES: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. METHODS: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. RESULTS: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). CONCLUSIONS: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery.

Using functional MRI (fMRI) we investigated 13 upper limb amputees with phantom limb pain (PLP) during hand and lip movement, before and after intensive 6-week training in mental imagery. Prior to training, activation elicited during lip purse showed evidence of cortical reorganization of motor (M1) and somatosensory (S1) cortices, expanding from lip area to hand area, which correlated with pain scores. In addition, during imagined movement of the phantom hand, and executed movement of the intact hand, group maps demonstrated activation not only in bilateral M1 and S1 hand area, but also lip area, showing a two-way process of reorganization. In healthy participants, activation during lip purse and imagined and executed movement of the non-dominant hand was confined to the respective cortical representation areas only. Following training, patients reported a significant reduction in intensity and unpleasantness of constant pain and exacerbations, with a corresponding elimination of cortical reorganization. Post hoc analyses showed that intensity of constant pain, but not exacerbations, correlated with reduction in cortical reorganization. The results of this study add to our current understanding of the pathophysiology of PLP, underlining the reversibility of neuroplastic changes in this patient population while offering a novel, simple method of pain relief.

Volunteer studies in pain research--opportunities and challenges to replace animal experiments: the report and recommendations of a Focus on Alternatives workshop.

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies and challenges of replacing some animal experiments in pain research with ethically conducted studies of human patients and healthy volunteers, in combination with in vitro methods. This report considers how a range of neuroimaging techniques including functional magnetic resonance imaging, magnetoencephalography and positron emission tomography, singly and combined, can address human pain conditions. In addition, microdialysis in human subjects; genome-wide association research, twin studies and other epidemiological approaches; and in vitro cell and tissue research, are examined for their replacement potential in combination with neuroimaging. Recommendations highlight further opportunities to advance the replacement of animal studies with robust methods of relevance to understanding and treating human pain.

AAN-EFNS guidelines on trigeminal neuralgia management.

Several issues regarding diagnosis, pharmacological treatment, and surgical treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy of Neurology and the European Federation of Neurological Societies launched a joint Task Force to prepare general guidelines for the management of this condition. After systematic review of the literature the Task Force came to a series of evidence-based recommendations. In patients with TN MRI may be considered to identify patients with structural causes. The presence of trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal reflexes should be considered useful to disclose symptomatic TN, whereas younger age of onset, involvement of the first division, unresponsiveness to treatment and abnormal trigeminal evoked potentials are not useful in distinguishing symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) should be offered as first-line treatment for pain control. For patients with TN refractory to medical therapy early surgical therapy may be considered. Gasserian ganglion percutaneous techniques, gamma knife and microvascular decompression may be considered. Microvascular decompression may be considered over other surgical techniques to provide the longest duration of pain freedom. The role of surgery versus pharmacotherapy in the management of TN in patients with multiple sclerosis remains uncertain.

Altered theta oscillations in resting EEG of fibromyalgia syndrome patients.

BACKGROUND: Fibromyalgia syndrome (FM) is a chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms. Functional imaging studies have revealed that FM and other chronic pain syndromes can affect resting brain activity. This study utilized electroencephalographic (EEG) recordings to investigate the relative power of ongoing oscillatory activity in the resting brain. METHODS: A 64-channel EEG was recorded at rest in 19 female FM patients and 18 healthy, age-matched, control subjects. The Manual Tender Point Scale (MTPS) examination was performed to quantify tonic pain and tenderness on the day of testing along with measures of mood, arousal and fatigue. Oscillations in delta, theta, alpha, beta and gamma frequency bands were analysed using Standardised Low-Resolution Brain Electromagnetic Tomography to evaluate sources of spectral activity throughout the whole brain. RESULTS: FM patients exhibited greater pain, tiredness and tension on the day of testing relative to healthy control participants and augmented theta activity in prefrontal and anterior cingulate cortices. No significant differences were seen in other frequency bands. Augmented frontal theta activity in FM patients significantly correlated with measures of tenderness and mean tiredness scores. CONCLUSIONS: The findings indicate that alterations to resting-state oscillatory activity may relate to ongoing tonic pain and fatigue in FM, and manifest in brain regions relevant for cognitive-attentional aspects of pain processing and endogenous pain inhibition. Enhanced low-frequency oscillations were previously seen in FM and other chronic pain syndromes, and may relate to pathophysiological mechanisms for ongoing pain such as thalamocortical dysrhythmia. SIGNIFICANCE: Increased prefrontal theta activity may contribute to persistent pain in fibromyalgia or represent the outcome of prolonged symptoms. The findings point to the potential for therapeutic interventions aimed at normalizing neural oscillations, while further research utilizing quantitative analysis of resting EEG could benefit our understanding of fibromyalgia pathophysiology.

Superiority of capsaicin 8% patch versus oral pregabalin on dynamic mechanical allodynia in patients with peripheral neuropathic pain.

BACKGROUND: Dynamic Mechanical Allodynia (DMA) is a typical symptom of neuropathic pain (NP). In a recent study, the capsaicin 8% patch was noninferior to pregabalin in overall peripheral NP relief. In this study, we report the comparison of the two treatments in relieving DMA. METHODS: In a randomized, open-label, head-to-head, 8-week study, 488 patients with peripheral NP were treated with the capsaicin 8% patch (one application) or an optimized dose of pregabalin. Assessments included the area and intensity of DMA, and the number of patients achieving complete resolution of DMA. RESULTS: At baseline, 253 patients in the capsaicin 8% patch group and 235 patients in the pregabalin group had DMA. From baseline to end of study, the change in DMA intensity was significantly in favour of the capsaicin 8% patch versus pregabalin [-0.63 (95% CI: -1.04, -0.23; p = 0.002)]. Similarly, the capsaicin 8% patch was superior to pregabalin in reducing the area of DMA [-39.5 cm2 (95% CI: -69.1, -10.0; p = 0.009)] from baseline to end of study. Overall, a greater proportion of patients had a complete resolution of allodynia with capsaicin 8% patch treatment compared with pregabalin treatment (24.1% vs. 12.3%; p = 0.001) at end of study. CONCLUSION: Capsaicin 8% treatment was superior to pregabalin in reducing the intensity and area of DMA, and in the number of patients with complete resolution of DMA. SIGNIFICANCE: The superiority of a topical treatment over pregabalin in relieving DMA supports the view that both peripheral and central sensitization can mediate allodynia.

EFNS guidelines on pharmacological treatment of neuropathic pain.

Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools.

Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain.

BACKGROUND: Clinical trials have not yet compared the efficacy of capsaicin 8% patch with current standard therapy in peripheral neuropathic pain (PNP). OBJECTIVES: Head-to-head efficacy and safety trial comparing the capsaicin patch with pregabalin in PNP. METHODS: Open-label, randomized, multicentre, non-inferiority trial. Patients with PNP, aged 18-80 years, were randomly assigned to either the capsaicin 8% patch (n = 282) or an optimised dose of oral pregabalin (n = 277), and assessed for a ≥30% mean decrease in Numeric Pain Rating Scale (NPRS) score from baseline to Week 8. Secondary endpoints included optimal therapeutic effect (OTE), time-to-onset of pain relief and treatment satisfaction. RESULTS: The capsaicin 8% patch was non-inferior to pregabalin in achievement of a ≥30% mean decrease in NPRS score from baseline to Week 8 (55.7% vs. 54.5%, respectively; Odds ratio: 1.03 [95% CI: 0.72, 1.50]). The proportion of patients achieving OTE at Week 8 was 52.1% for the capsaicin 8% patch versus 44.8% for pregabalin (difference: 7.3%; 95% CI: -0.9%, 15.6%). The median time-to-onset of pain relief was significantly shorter for capsaicin 8% patch versus pregabalin (7.5 vs. 36.0 days; Hazard ratio: 1.68 [95% CI: 1.35, 2.08]; p < 0.0001). Treatment satisfaction was also significantly greater with the capsaicin 8% patch versus pregabalin. TEAEs were mild-to-moderate in severity, and resulted in treatment discontinuation only with pregabalin (n = 24). Systemic adverse drug reactions ranged from 0 to 1.1% with capsaicin 8% patch and 2.5 to 18.4% with pregabalin. CONCLUSIONS: The capsaicin 8% patch provided non-inferior pain relief to an optimized dose of pregabalin in PNP, with a faster onset of action, fewer systemic side effects and greater treatment satisfaction.

Altered cutaneous sensation in trigeminal neuralgia.

Noninvasive quantitative somatosensory tests were used to measure sensory perception thresholds on the faces of 26 patients with idiopathic trigeminal neuralgia. The affected divisions were determined by the presence of trigger zones. Elevations of thresholds of sensations subserved by both large- and small-diameter fibers were found both in the affected and in the unaffected adjacent divisions when compared with the healthy side. The findings are interpreted as further evidence of combined peripheral and central pathologic conditions in idiopathic trigeminal neuralgia.

Clinical features and pathophysiologic mechanisms of postherpetic neuralgia.

Postherpetic neuralgia is an unfortunate aftermath of shingles, and is most likely to develop, and most persistent, in elderly patients. Pain, allodynia, and sensory loss in the affected dermatome are the cardinal manifestations of the disorder. The pathophysiology of postherpetic neuralgia is not well known, but recent observations suggest multiple changes in the afferent pathways at both peripheral and central nervous system levels.

Celiac disease, brain atrophy, and dementia.

We report 5 patients who developed dementia before age 60 and were subsequently found to have celiac disease (CD). Intellectual deterioration ranged from moderate to severe, and diffuse cerebral or cerebellar atrophy was found on brain CT. Diagnosis of CD was confirmed by findings of subtotal villous atrophy in jejunal biopsy specimens and positive serum reticulin and gliadin antibodies. Conspicuously, gastrointestinal symptoms were mild. The gluten-free diet failed to improve the neurologic disability except in 1 patient. CD is a multisystem disorder and may play a role in some cases of presenile dementia. Although the pathogenetic mechanisms are obscure, immunologic mechanisms are implicated.

CSF and MRI findings in patients with acute herpes zoster.

OBJECTIVE: To explore MRI and CSF findings in patients with herpes zoster (HZ) and to correlate the findings with clinical manifestations of the disease. METHODS: Fifty immunocompetent patients (mean age, 59 years; range, 17 to 84 years) with HZ of fewer than 18 days duration participated. None had clinical signs of meningeal irritation, encephalitis, or myelitis. In 42 patients (84%), the symptoms constituted pain and rash only. Six patients (12%) had motor paresis, and three patients (6%) had ocular complications. One to three CSF samples were obtained from 46 patients (the first sampling taken 1 to 18 days from onset of rash), and 16 patients (all with either trigeminal or cervical HZ) underwent MRI of the brain. The clinical follow-up continued at least 3 months. RESULTS: CSF was abnormal in 28/46 patients (61%): pleocytosis (range, 5 to 1,440 microL) was detected in 21, elevated protein concentration in 12, varicella zoster virus (VZV) DNA in 10, and immunoglobulin G antibody to VZV in 10. These changes were more common in patients with acute complications, although they did not predict development of postherpetic neuralgia (PHN). In 9/16 patients (56%), MRI lesions attributable to HZ were seen in the brainstem and cervical cord. At 3 months, 5/9 patients (56%) with abnormal MRI had PHN, whereas none of the 7 patients with no HZ-related lesions on MRI had any remaining pain. CONCLUSIONS: Subclinical extension of viral inflammation into the CNS occurs commonly in HZ. This finding may have implications for treatment of HZ and prevention of various associated complications.

Pain in spasmodic torticollis.

Spasmodic torticollis (cervical dystonia) is frequently a painful condition but little is known of the characteristics of the pain. We assessed 39 patients with spasmodic torticollis for the presence or absence, location, and quality of pain, as well as its correlation to postural abnormality. Muscle tenderness was evaluated by manual palpation and pressure algometry. Measurements were made on muscles either actively maintaining or opposing abnormal head posture, as well as on muscles not contributing to it. Control measurements were made in 18 healthy subjects. Two-thirds of patients reported continuous or intermittent recurrent pain. Pain was reported widespread and diffuse over the neck and shoulders, with some radiation, predominantly on the side toward which the head was twisted. There were no differences between study groups when compared for pressure algometry and only moderate differences when compared for manual palpation. No correlation was found between the severity of motor signs and pain. Degenerative changes seen on X-rays were similar in painful and pain-free patients. These findings suggest that pain associated with spasmodic torticollis does not arise in muscles alone, and we hypothesise that central mechanisms are also involved.

Allodynia and pinprick hypesthesia in acute herpes zoster, and the development of postherpetic neuralgia.

Sensory loss and allodynia are hallmark signs of postherpetic neuralgia (PHN). We set out to investigate how frequently these signs are present in patients with acute herpes zoster (HZ) and what their prognostic value might be. We assessed pain, mechanical allodynia, and sensitivity to pinprick in 113 immunocompetent patients with HZ of a median duration of 5 days. Follow-up visits took place at 2 weeks, 6 weeks, 3 months, and 6 months. When first seen, 87 (77%) patients reported ongoing pain and 48/107 (45%) had allodynia. Twenty-eight (25%) patients had pain at 3 months (and were considered to have developed PHN), while 14 (12%) patients had pain at 6 months. Allodynia tended to subside quickly in most patients. Reduced sensitivity to pinprick was less common. Mechanical allodynia and pinprick hypesthesia were strongly associated with the development of PHN. They merit addition to the list of potential risk factors for PHN although they cannot be used as a predictive rule for an individual patient. By contrast, lack of allodynia in the early stages of HZ predicts good recovery by three months.

Mechanisms of central pain.

Central pain is common in patients with stroke, multiple sclerosis, syringomyelia, and spinal cord injury. It frequently develops after a delay of weeks or months, is associated with sensory change involving the spinothalamic pathways, and has a poor prognosis for spontaneous remission. Hypotheses to explain the varied clinical manifestations can be divided in two categories: those stressing aberrant neural activity in the deafferented circuits and those focusing on the postlesion imbalance between facilitatory and inhibitory neural pathways. All models inherently assume a degree of specialization of cerebral structures in pain processing, which has not been proved conclusively.

Pain and somatosensory dysfunction in acute herpes zoster.

OBJECTIVE: To determine the nature of sensory change and its association with pain and allodynia in acute herpes zoster. DESIGN: Prospective clinical study. PATIENTS: One hundred thirteen immunocompetent patients with acute herpes zoster. METHODS: Onset, intensity, and quality of pain and severity of rash were recorded. Quantitative somatosensory testing for tactile and thermal thresholds, qualitative pinprick testing, and testing of dynamic and static allodynia were performed within the affected dermatome, its mirror-image dermatome, and in an adjacent dermatome bilaterally. RESULTS: Acute pain was reported as severe in 50%, moderate in 29%, mild in 12%, and absent in 9% of patients. Preherpetic pain (median = 4 days, range = 1-60 days) was experienced by 71%. Mechanical allodynia, dynamic, static, or both, was found in 37% of patients and was noted to extend one or more dermatomes outside the rash in 12%. In the affected dermatomes, thresholds were elevated for warmth and cold, lowered for heat pain, and unchanged for touch when compared with the contralateral side. Logistic regression analyses showed that compression-evoked allodynia, brush-evoked allodynia, and the history of preherpetic pain were more frequently encountered in patients with severe pain. Sensory threshold changes were not associated with the severity of pain or rash or with the presence of allodynia. CONCLUSION: Pain, allodynia, and altered sensation are common features of acute herpes zoster. They are likely to result primarily from widespread neural inflammation within the affected afferent system. The sensory changes found in acute herpes zoster are different from those reported in published studies on postherpetic neuralgia and suggest sensitization phenomena and preservation of tactile functions rather than major neural damage. The exact mechanisms for acute herpes zoster pain, however, remain speculative.

Clinical and neurophysiological observations on acute herpes zoster.

We studied 31 patients with acute herpes zoster (AHZ) less than 28 days' duration. Clinical characteristics (pain, allodynia, course of disease) and somatosensory perception thresholds (thermal discrimination, hot pain, and vibration) of the affected dermatome and the contralateral homologous area were assessed. Touch-evoked allodynia was found in 17 (55%) and dysesthesia in a further 5 (16%). Thermal and vibration perception thresholds demonstrated significant elevations when compared to the contralateral side. Thermal threshold abnormalities were significantly associated with the prevalence of postherpetic neuralgia (PHN) at 3 months. The effect of nerve blockade was less favorable on allodynia than spontaneous pain. The results of possible pathophysiological mechanisms are discussed.