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Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis.

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Molecular Determinants of μ-Conotoxin KIIIA interaction with the Voltage-Gated Sodium Channel Nav1.7.

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VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA.

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Clinical features of visual migraine aura: a systematic review.

Migraine aura (MA) is a common and disabling neurological condition, characterized by transient visual, and less frequently sensory and dysphasic aura disturbances. MA is associated with an increased risk of cardiovascular disorders and is often clinically difficult to distinguish from other serious neurological disorders such as transient ischemic attacks and epilepsy. Optimal clinical classification of MA symptoms is important for more accurate diagnosis and improved understanding of the pathophysiology of MA through clinical studies.

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Dural calcitonin gene-related peptide produces female-specific responses in rodent migraine models.

Migraine is the second leading cause for disability worldwide and the most common neurological disorder. It is also three times more common in women; reasons for this sex difference are not known. Using preclinical behavioral models of migraine, we show that application of CGRP to the rat dura mater produces cutaneous periorbital hypersensitivity. Surprisingly, this response was observed only in females; dural CGRP at doses from 1 pg to 3.8 μg produce no responses in males. In females, dural CGRP causes priming to a pH 7.0 solution after animals recover from the initial CGRP-induced allodynia. Dural application of interleukin-6 (IL-6) causes acute responses in males and females but only causes priming to subthreshold dural CGRP (0.1 pg) in females. Intracisternal application of BDNF also causes similar acute hypersensitivity responses in males and females but only priming to subthreshold dural CGRP (0.1 pg) in females. Females were additionally primed to a subthreshold dose of the NO-donor sodium nitroprusside (0.1 mg/kg) following dural CGRP. Finally, the sexually-dimorphic responses to dural CGRP were not specific to rats as similar female-specific hypersensitivity responses were seen in mice, where increased grimace responses were also observed. These data are the first to demonstrate that CGRP induced headache-like behavioral responses at doses up to 3.8 μg are female specific both acutely and following central and peripheral priming. These data further implicate dural CGRP signaling in the pathophysiology of migraine and propose a model where dural CGRP-based mechanisms contribute to the sexual disparity of this female biased disorder.Calcitonin gene-related peptide has long been implicated in the pathophysiology of migraine and CGRP-based therapeutics are efficacious for the treatment of migraine in humans. However, the location of action for CGRP in migraine remains unclear. We show here that application of CGRP to the cranial meninges causes behavioral responses consistent with headache in preclinical rodent models. Surprisingly however, these responses are only observed in females. Acute responses to meningeal CGRP are female-specific and sensitization to CGRP after two-distinct stimuli are also female-specific. These data implicate the dura mater as a primary location of action for CGRP in migraine and suggest that female-specific mechanisms downstream of CGRP receptor activation contribute to the higher prevalence of migraine in women.

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A dual role for peripheral GDNF signaling in nociception and cardiovascular reflexes.

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Recent Progress in TRPM8 Modulation: An Update.

The transient receptor potential melastatin subtype 8 (TRPM8) is a nonselective, multimodal ion channel, activated by low temperatures (<28 °C), pressure, and cooling compounds (menthol, icilin). Experimental evidences indicated a role of TRPM8 in cold thermal transduction, different life-threatening tumors, and other pathologies, including migraine, urinary tract dysfunction, dry eye disease, and obesity. Hence, the modulation of the TRPM8 channel could be essential in order to understand its implications in these pathologies and for therapeutic intervention. This short review will cover recent progress on the TRPM8 agonists and antagonists, describing newly reported chemotypes, and their application in the pharmacological characterization of TRPM8 in health and disease. The recently described structures of the TRPM8 channel alone or complexed with known agonists and PIP are also discussed.

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Opioid-galanin receptor heteromers differentiate the dopaminergic effects of morphine and methadone.

As the opioid addiction crisis reaches epidemic levels, the identification of opioid analgesics that lack abuse potential may provide a path to safer treatment of chronic pain. Preclinical studies have demonstrated that galanin affects physical dependence and rewarding actions associated with morphine. In the brain and periphery, galanin and opioids signal through their respective GPCRs, GalR1-3 and the μ-opioid receptor (MOR). In this issue of the JCI, Cai and collaborators reveal that heteromers between GalR1 and MOR in the rat ventral tegmental area attenuate the potency of methadone, but not other opioids, in stimulating the dopamine release that produces euphoria. These studies help us understand why some synthetic opioids, such as methadone, do not trigger the release of dopamine in the mesolimbic system but still possess strong analgesic properties.

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Aberrant interactions of cortical networks in chronic migraine: A resting-state fMRI study.

We investigated resting-state (RS)-fMRI using independent component analysis (ICA) to determine the functional connectivity (FC) between networks in chronic migraine (CM) patients and their correlation with clinical features.

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Tramadol for osteoarthritis.

Tramadol is often prescribed to treat pain and is associated physical disability in osteoarthritis (OA). Due to the pharmacologic mechanism of tramadol, it may lead to fewer associated adverse effects (i.e. gastrointestinal bleeding or renal problems) compared to non-steroidal anti-inflammatory drugs (NSAIDs). This is an update of a Cochrane Review originally published in 2006.

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