Cephalalgia : an international journal of headache
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The importance of neck pain and the trigeminocervical complex in migraine is of high pathophysiological interest since a block to the greater occipital nerve is more effective for some primary headaches than others. This observational study hypothesised that the response to manual palpation of the upper cervical spine predicts the efficacy of the greater occipital nerve-block. ⋯ Patients that were less sensitive to palpation in the cervical region and headache-free on the day of the intervention improved more after the greater occipital nerve-block.Registration: Registered a priori at the German Clinical Trials Register (DRKS00015995).
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Migraine pain is thought to result from activation of meningeal nociceptors that might involve dural mast cell degranulation and release of proteases and pronociceptive mediators. Tryptase, the most abundant dural mast cell protease, has been demonstrated to stimulate dural mast cells, as well as trigeminal nociceptors by activating the protease activated receptor 2. Mast cell or neuronal protease activated receptors 2 may therefore represent a novel target for migraine treatment. In this study, we characterized and evaluated a novel protease activated receptor 2 monoclonal antibody as a preventive anti-migraine pain therapy in preclinical models. ⋯ PAR650097 specifically inhibits endogenously expressed protease activated receptor 2 in human and mouse cells with high potency. This antibody has an acceptable PK profile in rodents and effectively blocked SLIGR-induced cutaneous allodynia. PAR650097 additionally prevented cutaneous allodynia induced by supradural calcitonin gene-related peptide, indicating that the protease activated receptor 2 receptor is a downstream consequence of calcitonin gene-related peptide actions. Fremanezumab effectively blocked calcitonin gene-related peptide-induced cutaneous allodynia and only partially reduced cutaneous allodynia induced by a protease activated receptor 2 activator, suggesting both calcitonin gene-related peptide-dependent and -independent mechanisms in promoting migraine pain. While PAR650097 did not prevent stress-induced cutaneous allodynia or priming, it effectively prevented cutaneous allodynia induced by a TRPA1 agonist in animals with latent sensitization. Activation of protease activated receptor 2, therefore, contributes to both calcitonin gene-related peptide-dependent and -independent mechanisms in promoting migraine-like pain. Therapeutic targeting of protease activated receptor 2 receptors may represent an anti-migraine pain strategy with a potentially broad efficacy profile.
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This study estimates the socioeconomic impact of migraine headaches on paid and unpaid work productivity in the adult German population in 1 year. ⋯ In addition to time losses in paid work, migraine causes substantial socioeconomic losses to unpaid work activities due to its disproportionate prevalence among females. Economic value chain effects provide a novel perspective on losses beyond a patient's time loss. Overall, the elements of socioeconomic burden provide a strong rationale that innovative migraine therapies could be of high value to society.
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To assess the frequency and characteristics of headache in patients with COVID-19 and whether there is an association between headache and anosmia and ageusia. ⋯ Headaches associated with COVID-19 are frequent, are generally severe, diffuse, present a migraine phenotype and are associated with anosmia and ageusia.
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Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30). ⋯ Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.