Bone pain is the most common type of pain from cancer and is present in around one third of patients with bone metastases, currently, improvements in cancer treatments mean that many patients are living with metastatic cancer for several years. Christopher Kane, NIHR academic clinical fellow in palliative medicine at Leeds University School of...

Our latest debate asks, should doctors recommend acupuncture for pain? Asbjørn Hróbjartsson from the Center for Evidence-based Medicine at University of Southern Denmark argues no - evidence show's it's no worse than placebo. Mike Cummings, medical director of the British Medical Acupuncture Society argues yes - that there is evidence of efficacy,...

It was a double whammy of inconvenience for Sharon Carter, a vendor in Metcalfe Market, Annotto Bay. Carter, who lives in St Catherine, had just recently been relieved of the lockdown in the parish and is now being affected by the quarantine which...

This report discusses Spain’s changing migration patterns in the wake of dramatic economic downturn, paying special attention to the effects of the emigration of young, native-born Spaniards. The report also focuses on policies geared toward engaging the increasing number of Spaniards abroad, finding that much of Spain's policy towards diasporas predates the 1980s.

OBJECTIVE

To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.

David J. Meier
Oct 1, 2001; 19:
Case Studies

Jan 1, 2013; 31:46-46
Patient Information

George D. Harris
Jul 1, 2007; 25:115-118
Case Studies

Here’s my Q&A column from the WSJ this week — and if you have any questions for me, you can tweet them to @danariely with the hashtag #askariely, post a comment on my Ask Ariely Facebook page, or email them to AskAriely@wsj.com. ___________________________________________________ Dear Dan, I shop at two different grocery...

A relatively new destination for immigrants, Spain has developed a labor migration system that builds on longstanding relationships with countries outside the European Union and that actively involves employers, trade unions, and regional governments. This report examines how this legal framework has evolved in recent decades, and how it could serve as a model for EU policymakers in admitting non-EU workers.

Here's a question with three different answers. The first answer is derived from arithmetic. The second comes from common sense. The third is based on psychology.

Lorenzo Rinaldo
Jul 1, 2017; 35:126-131
Feature Articles

London (46 Pall Mall) : Pub.d by R. Bowyer & M. Parkes, 1st Jan.y 1830.

[Rome?]

A Paris (rue St Jacques au dessus de celle des Mathurins au Gd. St. Remy : ches Huquier fils, graveur, [between 1700 and 1799]

A Paris (rue St. Jacques au dessus de la fontaine St Severin aux 2 colonne no 257) : chez J. Chereau, [between 1700 and 1799]

2005.

[London] : [Wellcome Trust], [2009]

Rockville, Maryland : National Institute on Drug Abuse, 1981.

Rockville, Maryland : National Institute on Drug Abuse, 1983.

Adam J. Krause
Mar 20, 2019; 39:2291-2300
BehavioralSystemsCognitive

The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.

SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.

One of the first signs of viral infection is body-wide aches and pain. Although this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization is well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I IFNs stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double-stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. Although specific mechanisms have been discovered for diverse bacterial and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type I interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling), which is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity

Calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, are widely used as standard immunosuppressants in organ transplantation recipients. However, these drugs can cause severe pain in patients, commonly referred to as calcineurin inhibitor-induced pain syndrome (CIPS). Although calcineurin inhibition increases NMDAR activity in the spinal cord, the underlying mechanism remains enigmatic. Using an animal model of CIPS, we found that systemic administration of FK506 in male and female mice significantly increased the amount of α2-1–GluN1 complexes in the spinal cord and the level of α2-1–bound GluN1 proteins in spinal synaptosomes. Treatment with FK506 significantly increased the frequency of mEPSCs and the amplitudes of monosynaptic EPSCs evoked from the dorsal root and puff NMDAR currents in spinal dorsal horn neurons. Inhibiting α2-1 with gabapentin or disrupting the α2-1–NMDAR interaction with α2-1Tat peptide completely reversed the effects of FK506. In α2-1 gene KO mice, treatment with FK506 failed to increase the frequency of NMDAR-mediated mEPSCs and the amplitudes of evoked EPSCs and puff NMDAR currents in spinal dorsal horn neurons. Furthermore, systemic administration of gabapentin or intrathecal injection of α2-1Tat peptide reversed thermal and mechanical hypersensitivity in FK506-treated mice. In addition, genetically deleting GluN1 in dorsal root ganglion neurons or α2-1 genetic KO similarly attenuated FK506-induced thermal and mechanical hypersensitivity. Together, our findings indicate that α2-1–bound NMDARs mediate calcineurin inhibitor-induced tonic activation of presynaptic and postsynaptic NMDARs at the spinal cord level and that presynaptic NMDARs play a prominent role in the development of CIPS.

SIGNIFICANCE STATEMENT Calcineurin inhibitors are immunosuppressants used to prevent rejection of transplanted organs and tissues. However, these drugs can cause severe, unexplained pain. We showed that calcineurin inhibition enhances physical interaction between α2-1 and NMDARs and their synaptic trafficking in the spinal cord. α2-1 is essential for calcineurin inhibitor-induced aberrant activation of presynaptic and postsynaptic NMDARs in the spinal cord. Furthermore, inhibiting α2-1 or disrupting α2-1–NMDAR interaction reduces calcineurin inhibitor-induced pain hypersensitivity. Eliminating NMDARs in primary sensory neurons or α2-1 KO also attenuates calcineurin inhibitor-induced pain hypersensitivity. This new information extends our mechanistic understanding of the role of endogenous calcineurin in regulating synaptic plasticity and nociceptive transmission and suggests new strategies for treating this painful condition.

Researchers lifted the ancient Egyptian mummy out of her coffin for the first time in 100 years and, to their surprise, uncovered the ancient artworks

He was talented and prosperous, but the young visionary worried the art world had left him behind. Then he discovered soup

A Guanaco (Lama guanicoe) surveys its surroundings from a vantage point at sunset, with the imposing Torres del Paine (Chile) in the background. Scouts like this individual keep an eye out for predators.

Doug Flutie can feel CFL commissioner Randy Ambrosie's pain as Ambrosie continues to discuss potential contingency plans for the 2020 CFL season in response to the COVID-19 pandemic.

London, England, May 1, 2020 / 05:00 am (CNA).- The metropolitan archbishops of England and Wales acknowledged the pain of Catholics who cannot receive the sacraments because of the coronavirus lockdown in a message issued Friday. 

In the message, entitled “A People who Hope in Christ”, published May 1, the archbishops said that while livestreamed Masses nourished faith, they were no substitute for public liturgies.

“None of us would want to be in the situation in which we find ourselves,” they wrote. “While the livestreaming of the Mass and other devotions is playing an important part in maintaining the life of faith, there is no substitute for Catholics being able to physically attend and participate in the celebration of the Mass and the other sacraments.”

Writing on behalf of the Catholic bishops of England and Wales, the five archbishops continued: “Our faith is expressed powerfully and beautifully though ‘seeing, touching, and tasting.’ We know that every bishop and every priest recognizes the pain of Catholics who, at present, cannot pray in church or receive the sacraments. This weighs heavily on our hearts.” 

“We are deeply moved by the Eucharistic yearning expressed by so many members of the faithful. We thank you sincerely for your love for the Lord Jesus, present in the sacraments and supremely so in the Holy Sacrifice of the Mass.” 

“The bishops and priests of every diocese are remembering you and your loved ones at Mass each day in our churches as we pray ‘in hope of health and well-being.’ We thank our priests for this faithfulness to their calling.”

Nevertheless, the archbishops said, the Catholic community had to play its part in preserving life and seeking the common good amid the pandemic. Restrictions on public liturgies would therefore have to remain in place until they are lifted by the government.

The U.K. is among the countries worst affected by the pandemic. With a population of 67 million, the U.K has had more than 172,000 documented coronavirus cases and 26,700 deaths as of May 1, according to Johns Hopkins University Coronavirus Resource Center.

The archbishops emphasized that Church officials were in talks with public health agencies and the government about the reopening of churches, which were closed March 24. 

“As the government’s restrictions are relaxed step by step, we look forward to opening our churches and resuming our liturgical, spiritual, catechetical and pastoral life step by step,” they said. 

“This will also be of service to those beyond the Catholic Church who depend on our charitable activity and outreach through which much goodness is shared by so many volunteers from our communities...”

“Together with Catholics across England and Wales, we desire the opening of our churches and access to the sacraments. Until then, we are continuing to pray and prepare.”

The message was signed by Cardinal Vincent Nichols of Westminster, Archbishop Malcolm McMahon of Liverpool, Archbishop Bernard Longley of Birmingham, Archbishop George Stack of Cardiff and Archbishop John Wilson of Southwark.

The archbishops concluded: “May the peace of the risen Lord reign in our hearts and homes as we look forward to the day we can enter church again and gather around the altar to offer together the Sacrifice of Praise.”

God answers a long-term worker’s prayer for an outreach day in Spain, connecting her with people from her host country in North Africa.

God uses a Latino-American couple to gather and train local believers, who form a small church in North Africa.

God uses a Latino-American couple to gather and train local believers, who form a small church in North Africa.

We find out how youngsters in Spain are taught a certain playing style from an early age.

We investigate a golden era of Spanish youth football.

Castilla y León made an impressive start to their bid for a second UEFA Regions' Cup title as two goals from Roberto García Puente set them on course for a 4-1 victory.

OF course, it’s a ridiculous idea. The 10 best Scottish paintings. As if anyone could choose. But if you take the folly of it as read, well, then, why not? See it as a game. A declaration of taste and bias, prejudice and ignorance and, more than likely, stupidity. Something to argue with at the very least. A list to incite your own counterblast.

Preterm infants are exposed to inadequately managed painful procedures during their NICU stay, which can lead to altered pain responses. Nonpharmacologic approaches are established for the treatment of single painful procedures, but evidence for their effectiveness across time is lacking.

Oral sucrose with or without the added technique of facilitated tucking has a pain-relieving effect even in extremely premature infants undergoing repeated pain exposures; facilitated tucking alone seems to be less effective for repeated pain exposures over time. (Read the full article)

Active termination of life in newborns with myelomeningocele because of assumed suffering in these newborns has been extensively discussed. However, the level of discomfort and pain in these newborns has never been substantially assessed.

This is the first study presenting quantitative data on discomfort and pain in newborns with myelomeningocele. Therefore, it can be of guidance in the choice of treatment: either active treatment or palliative care in the context of end-of-life decisions. (Read the full article)

Numerous late preterm infants undergo repetitive heel lancing procedures during their first hours of life to evaluate glycemic control. Heel lances are painful and 25% glucose solution is effective on reducing procedural neonatal pain scores and crying behavior.

This noninferiority randomized controlled trial demonstrated that compared with breast milk, 25% glucose provided lower pain scores and reduced duration of cry. Further research is necessary to clarify breast milk’s mechanisms and efficacy on neonatal pain relief. (Read the full article)

Disparities are known to exist in the prescription of opioid analgesics among racial and ethnic groups in the management of postoperative, cancer, and emergency department pain in patients across all ages, including children.

Race is associated with an unequal burden of perioperative pain and opioid adverse effects in children. Relatively, African American children had higher postoperative pain, and Caucasian children had higher incidences of opioid related adverse effects. (Read the full article)

The importance of and interest in childhood mental problems have increased worldwide. There are few population studies on child and adolescent mental health and health-related quality of life (HRQoL).

A social gradient was found in childhood mental health according to maternal education level and social class, but none was found in HRQoL, although children from disadvantaged social classes had somewhat lower HRQoL scores than their more advantaged counterparts. (Read the full article)

Increased computed tomography (CT) use among adults and children presenting to emergency departments has spawned concern about associated radiation exposure. The risks and benefits of CT use for certain conditions, such as abdominal pain, among general pediatric populations remains unclear.

This study analyzes emergency department radiology trends between 1998 and 2008 among children with abdominal pain, highlighting a dramatic increase in CT use. Factors associated with CT ordering include older age, non-black race, and hospital admission. (Read the full article)

Acquired widespread pain syndromes of youth are prevalent, disabling, usually unexplained, and untreatable. Small-fiber polyneuropathy causes widespread pain and multisystem complaints in older adults. Some causes are treatable. Neurodiagnostic skin biopsy, autonomic function testing, and nerve biopsy permit objective diagnosis.

It identifies definite (in 59%) and probable (in 17%) small-fiber polyneuropathy among 41 young patients with otherwise-unexplained, childhood-onset widespread pain. It characterizes this new disease’s clinical features, diagnostic, and treatment options. Some cases appeared immune mediated and responded to immunomodulatory therapies. (Read the full article)