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Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM.
Learn More >Chronic pain is one of the most prevalent and disabling symptoms associated with multiple sclerosis (MS). Individuals with MS are interested in nonpharmacologic pain management approaches. Cognitive-behavioral therapy (CBT) is efficacious in improving MS-related pain outcomes. Mindfulness-based cognitive therapy (MBCT) is a promising, alternative approach. Little is known about moderators of these treatments' outcomes, however. This article describes the study protocol for the first randomized controlled trial comparing MBCT, CBT, and usual care and examining treatment effect moderators in individuals with chronic pain and MS.
Learn More >People with migraine often experience disability with serious consequences for their social life and work productivity. The pharmacological prophylactic management of migraine is effective in reducing migraine attacks. However, many people are reluctant to use daily prophylactic medication, leading to a demand for non-pharmacological treatment options. We present the design for and discuss the feasibility of a pragmatic, randomized controlled trial on the effectiveness of a multimodal manual therapy (MT) treatment compared to usual care by the general practitioner (GP) for the prophylactic treatment of migraine.
Learn More >To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs).
Learn More >Spinal gastrin-releasing peptide receptor-expressing (GRPR) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR neurons. We found that spinal galanin GABAergic neurons form inhibitory synapses with GRPR neurons in the spinal cord and play an important role in gating the GRPR neuron-dependent itch signaling pathway. Spinal GRPR neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR neurons.
Learn More >Effective and safe analgesics represent an unmet medical need for the treatment of acute and chronic pain. A series of N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized and assayed, leading to the discovery of a benzylamine derivative (compound 4, SLL-039) as a highly selective and potent κ opioid agonist (κ, Ki=0.47 nM, κ/μ=682, κ/δ=283), which was confirmed by functional assays in vitro and antinociceptive assays in vivo. The in vivo effect could be blocked by pretreatment with the selective κ antagonist nor-BNI. Moreover, this compound did not induce sedation, a common dose limiting effect of κ opioid receptor agonists, at its analgesic dose compared to U50,488H. The dissociation of sedation/antinociception found in SLL-039 was assumed to be correlated with the occupation of its benzamide motif in a unique subsite involving V1182.63, W124EL1 and E209EL2.
Learn More >Observing successful pain treatment in others can induce anticipatory neural processes that, in turn, relieve pain. Previous studies have suggested that social learning and observation influence placebo hypoalgesia. Here, we used electroencephalography (EEG) to determine the neurophysiological changes associated with pain relief acquired through the observation. Thirty-one participants observed a demonstrator undergo painful heat stimulations paired with a "control" cream and non-painful ones paired with a "treatment" cream, which actually were both Vanicreams. After their observation, the participants then received the same creams and stimulations. We found that the treatment cream led to lower self-reported pain intensity ratings than the control cream. Anticipatory treatment cues elicited smaller P2 in electrodes F1, Fz, FC1, and FCz than the control condition. The P2 component localization indicated a higher current density in the right middle frontal gyrus, a region associated with attentional engagement. In placebo responders, the sensorimotor cortex activity captured in electrodes C3, Cz, and C4 indicated that hypoalgesia was positively correlated with resting state peak alpha frequency (PAF). These results suggest that observationally-induced placebo hypoalgesia may be driven by anticipatory mechanisms that modulate frontal attentional processes. Furthermore, resting state PAF could serve as a predictor of observationally-induced hypoalgesia.
Learn More >Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, rs10166942[C]) and rs10166942[T]) are more prevalent in populations that reside in hotter and colder climates, respectively. Here we assessed whether these alleles affect TRPM8 expression in humans and human physiologic responses to cold challenge. Here we show that TRPM8 expression is decreased from the chromosome harboring the rs10166942[C] allele in the human dorsal root ganglia. Moreover, carriers of rs10166942[C] required significantly lower temperatures and longer duration of exposure to reach a cold pain threshold (CPTh), which correlated with decreased TRPM8 expression expected in the carriers. This study provides evidence for a genotype-dependent influence on cold pain sensation suggesting that carriers of the reduced migraine risk allele have reduced sensitivity to cold stimuli and that TRPM8 acts as a cold thermosensor and cold pain transducer in humans. Reduced TRPM8 expression and function underpins the migraine protection in carriers of rs10166942[C]; thus, the evaluation of TRPM8 antagonists as migraine therapeutics is warranted. Furthermore, these results provide mechanistic insights for evolutionary positive selection of rs10166942[T] allele in adaptation along latitudinal cline to colder climates.
Learn More >Low back pain (LBP) is the most frequent complaint in clinical practice. Electroacupuncture treatment may be effective; however, the supporting evidence is still limited, especially in older adults.
Learn More >Understanding the mechanisms of migraine remains challenging as migraine is not a static disorder, and even in its episodic form migraine remains an "evolutive" chronic condition. Considerable progress has been made in elucidating the pathophysiological mechanisms of migraine, associated genetic factors that may influence susceptibility to the disease, and functional and anatomical changes during the progression of a migraine attack or the transformation of episodic to chronic migraine. Migraine is a life span neurological disorder that follows an evolutive age-dependent change in its prevalence and even clinical presentations. As a disorder, migraine involves recurrent intense head pain and associated unpleasant symptoms. Migraine attacks evolve over different phases with specific neural mechanisms and symptoms being involved during each phase. In some patients, migraine can be transformed into a chronic form with daily or almost daily headaches. The mechanisms behind this evolutive process remain unknown, but genetic and epigenetic factors, inflammatory processes and central sensitization may play an important role.
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