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Cluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15 min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster headache treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this is not always possible. Subcutaneous sumatriptan and high-flow oxygen are the most proven abortive treatments for cluster headache attacks, but other treatment options such as intranasal triptans may be effective. Verapamil and lithium are the preventive drugs of first choice and the most widely used in first-line preventive treatment. Given its possible cardiac side effects, electrocardiogram (ECG) is recommended before treating with verapamil. Liver and kidney functioning should be evaluated before and during treatment with lithium. If verapamil and lithium are ineffective, contraindicated or discontinued because of side effects, the second choice is topiramate. If all these drugs fail, other options with lower levels of evidence are available (e.g. melatonin, clomiphene, dihydroergotamine, pizotifen). However, since the evidence level is low, we also recommend considering one of several neuromodulatory options in patients with refractory chronic cluster headache. A new addition to the preventive treatment options in episodic cluster headache is galcanezumab, although the long-term effects remain unknown. Since effective preventive treatment can take several weeks to titrate, transitional treatment can be of great importance in the treatment of cluster headache. At present, greater occipital nerve injection is the most proven transitional treatment. Other options are high-dose prednisone or frovatriptan.
Learn More >Opioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians' knowledge and practices after completing the OSA package.
Learn More >Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial Direct Current Stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment.
Learn More >Non-specific chronic low back pain (CLBP) is a multifactorial disorder. Pain-related fear and altered movement preparation are considered to be key factors in the chronification process. Interactions between both have been hypothesized, but studies examining the influence of situational fear on movement preparation in low back pain (LBP) are wanting, as well as studies differentiating between recurrent LBP (RLBP) and CLBP. Therefore, this study examined whether experimentally induced pain-related fear influences movement preparation. In healthy controls (n=32), RLBP (n=31) and CLBP (n=30) patients central and peripheral measures of movement preparation were assessed by concurrently measuring trunk muscle anticipatory postural adjustments (APA) with EMG and Contingent Negative Variation (CNV) with EEG during performance of rapid arm movements (RAM). Two conditions were compared, one without (no fear) and one with (fear) possibility of painful stimulation to the back during RAM. Visual analogue scales were used to assess pain-related expectations/fear in both conditions. The experimentally induced fear of pain during movement performance led to an increase in CNV-amplitude, which was similar in all three groups. Concerning APAs no effects of fear were found, but group differences with generally delayed APAs in CLBP compared to controls and RLBP patients were evident. These results suggest that with fear an attentional redirection towards more conscious central movement preparation strategies occurs. Furthermore, differences in movement preparation in RLBP and CLBP patients exist, which could explain why RLBP patients have more recovery capabilities than CLBP.
Learn More >G-protein-coupled receptors (GPCRs) mediate a wide range of human physiological functions by transducing extracellular ligand binding events into intracellular responses. GPCRs can activate parallel, independent signaling pathways mediated by G proteins or β-arrestins. Whereas "balanced" agonists activate both pathways equally, "biased" agonists dominantly activate one pathway, which is of interest for designing GPCR-targeting drugs because it may mitigate undesirable side effects. Previous studies demonstrated that β-arrestin activation is associated with transmembrane helix VII (TM VII) of GPCRs. Here, single-molecule fluorescence spectroscopy with the β-adrenergic receptor (βAR) in the ligand-free state showed that TM VII spontaneously fluctuates between one inactive and one active-like conformation. The presence of the β-arrestin-biased agonist isoetharine prolongs the dwell time of TM VII in the active-like conformation compared with the balanced agonist formoterol, suggesting that ligands can induce signaling bias by modulating the kinetics of receptor conformational exchange.
Learn More >Patients with migraine have a co-morbidity with vascular diseases such as hypertension, coronary heart disease, and stroke.
Learn More >The loss of sensory input following a spinal deafferentation injury can be debilitating, and this is especially true in primates when the hand is involved. While significant recovery of function occurs, little is currently understood about the reorganization of the neuronal circuitry, particularly within the dorsal horn. This region receives primary afferent input from the periphery, and cortical input via the somatosensory subcomponent of the corticospinal tract (S1 CST), and is critically important in modulating sensory transmission, both in normal and lesioned states. To determine how dorsal horn circuitry alters to facilitate recovery post-injury, we used an established deafferentation lesion model (DRL/DCL – dorsal root/dorsal column) in male monkeys to remove sensory input from just the opposing digits (D1-D3) of one hand. This results in a deficit in fine dexterity that recovers over several months. Electrophysiological mapping, tract tracing, and immunolabeling techniques were combined to delineate specific changes to dorsal horn input circuitry. Our main findings show that (1) there is complementary sprouting of the primary afferent and S1 CST populations into an overlapping region of the reorganizing dorsal horn, (2) S1 CST and primary afferent inputs connect in different ways within this region to facilitate sensory integration (3) there is a loss of larger S1 CST terminal boutons in the affected dorsal horn, but no change in the size profile of the spared/sprouted primary afferent terminal boutons post-lesion. Understanding such changes helps to inform new and targeted therapies that best promote recovery.Spinal injuries that remove sensation from the hand, can be debilitating, though functional recovery does occur. We examined changes to the neuronal circuitry of the dorsal horn in monkeys following a lesion that deafferented three digits of one hand. Little is understood about dorsal horn circuitry, despite the fact that this region loses most of its normal input after such an injury, and is clearly a major focus of reorganization. We found that both the spared primary afferents and somatosensory corticospinal efferents sprouted in an overlapping region of the dorsal horn after injury, and that larger (presumably faster) corticospinal terminals are lost, suggesting a significantly altered cortical modulation of primary afferents. Understanding this changing circuitry is important for designing targeted therapies.
Learn More >The underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown beneficial effects on individuals suffering from chronic pain. Anxiety-prone rats exposed to water avoidance stress (WAS) develop urinary frequency and lower bladder sensory thresholds with high face and construct validity for the study of IC/BPS. The aim of this study was to evaluate the role of chronic voluntary exercise on urinary frequency, voiding function, and hyperalgesia in animals exposed to WAS.
Learn More >Chronic vulvar pain is a multidimensional condition with great variability in clinical presentation among affected women. In a companion article, part 1, we reviewed and recommended assessment and measurement tools for vulvar pain and related outcomes with a view toward improving consistency and comparison across studies. Yet methodological challenges to conducting research with this population remain and can further hinder conclusions regarding etiology and treatment.
Learn More >Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with other symptoms, including psychological distress. While negative mood (anxiety, depression, and anger) has been widely explored in FM, few studies have investigated emotional dysregulation. Our purpose was to evaluate problems in the processes of emotional regulation and to explore their influence on the severity of pain and disability.
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