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Capsaicin receptor, also known as transient receptor potential vanilloid 1 (TRPV1), is involved in pain physiology and neurogenic inflammation. Herein, we discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and aimed to delineate its function in this cell type and liver fibrosis.
Learn More >Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.
Learn More >Migraine is a type of headache with multiple neurological symptoms. Prior neuroimaging studies in patients with migraine based on functional magnetic resonance imaging have found regional as well as network-level alterations in brain function. Here, we expand on prior studies by establishing whole-brain functional connectivity patterns in patients with migraine using dimensionality reduction techniques. We studied functional brain connectivity in 50 patients with episodic migraine and sex- and age-matched healthy controls. Using dimensionality reduction techniques that project high-dimensional functional connectivity onto low-dimensional representations (i.e., eigenvectors), we found significant between-group differences in the eigenvectors between patients with migraine and healthy controls, particularly in the sensory/motor and limbic cortices. Furthermore, we assessed between-group differences in subcortical connectivity with subcortical weighted manifolds defined by subcortico-cortical connectivity multiplied by cortical eigenvectors and revealed significant alterations in the amygdala. Finally, leveraging supervised machine learning, we moderately predicted headache frequency using cortical and subcortical functional connectivity features, again indicating that sensory and limbic regions play a particularly important role in predicting migraine frequency. Our study confirmed that migraine is a hierarchical disease of the brain that shows alterations along the sensory-limbic axis, and therefore, the functional connectivity in these areas could be a useful marker to investigate migraine symptomatology.
Learn More >Chronic non-cancer pain can affect a patient's social life, ability to work, and overall quality of life (QoL). Opioid therapy is often prescribed as therapeutic treatment in chronic pain. Systematic reviews (SRs)-the pinnacle of research quality-are often used in guideline development; however, pain may differ across cultures and communities. Thus, examination of equity reporting in such SR is necessary. This study examines reporting using the PROGRESS (Place of resident, Race, Occupation, Gender, Religion, Education, Socioeconomic status, Social capital)-Plus framework to examine equity within SRs with patient reported outcomes of chronic, non-cancer pain. A systematic search for SRs was conducted, which were evaluated for PROGRESS-Plus items and study characteristics were extracted. Among the 46 included SRs, seven did not include any PROGRESS-Plus items. The most commonly reported items were , included within 34 SRs, followed by (30/46), and (14/46). All other items were reported in five or less studies. Our investigation revealed a deficiency in SR's reporting of equity measures for opioid treatment of chronic non-cancer pain. Given the need to address healthcare disparities among minorities, implementing the PROGRESS-Plus framework may influence QoL and patient-centered care.
Learn More >Trigeminal autonomic cephalalgias (TACs) comprise a unique collection of primary headache disorders characterized by moderate or severe unilateral pain, localized in in the area of distribution of the first branch of the trigeminal nerve, accompanied by cranial autonomic symptoms and signs. Most TACs are rare diseases, which hampers the possibility of performing randomized clinical trials and large studies. Therefore, knowledge of treatment efficacy must be based only on observational studies, rare disease registries, and case reports, where real-world data and evidence play an important role in health care decisions.
Learn More >Medications for preventive treatment of migraine reduce migraine frequency, usually measured by a reduction in monthly migraine days (MMD), but generally do not eliminate the need for acute treatment. To assess the economic impact of treatment-related reductions in frequency, methodological guidance recommends capturing cost differences along the spectrum of MMD.
Learn More >Previous studies suggested that the dorsal column of the periaqueductal grey matter (dPAG) can be a target of neural pathways from hypothalamic nuclei involved in triggering fear-related defensive responses. In turn, evidence is provided suggesting that microinjection of the nitric oxide (NO) donor SIN-1 into the anterior hypothalamus (AH) of mice evokes panic-like behaviours and fear-induced antinociception. However, it is unknown whether the dPAG of mice mediates these latter defensive responses organised by AH neurons.
Learn More >and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS). Whereas the analgesic effect of PAP has been attributed to a local effect on the mucosa of the lower urinary tract (LUT), the molecular targets of PAP remain unknown. We investigated the effect of PAP on pain-related Transient Receptor Potential (TRP) channels expressed in sensory neurons that innervate the bladder wall.
Learn More >Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1- and D2-expressing medium spiny neurons (Drd1- and Drd2-MSNs) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors, but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala or ventral hippocampus. Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of kappa opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.Itch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the NAc core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of kappa opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.
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