Genetic mutation causes low sensitivity to pain

A UCL-led research team has identified a rare mutation that causes one family to have unusually low sensitivity to pain. They studied an Italian family, the Marsilis, which includes six people who have a distinctive pain response that has not been identified in any other people. "The members of this family can burn themselves or experience pain-free bone fractures without feeling any pain. But they have a normal intraepidermal nerve fibre density, which means their nerves are all there, they're just not working how they should be. We're working to gain a better understanding of exactly why they don't feel much pain, to see if that could help us find new pain relief treatments," said the study's lead author, Dr James Cox (UCL Wolfson Institute for Biomedical Research).

One in ten people experience moderately to severely disabling chronic pain, but treatments beyond common painkillers remain elusive. Understanding the causes of congenital analgesia, a rare inherited condition that reduces the capacity to feel physical pain, is one of the main areas of research that could lead to new pain relief therapies. Two other mutations causing congenital analgesia are being actively explored by researchers alongside pharmaceutical firms, but have yet to yield any breakthrough drugs.

The research team added to previous work with the Italian family to clarify the nature of their phenotype (the observable characteristics caused by their genetics) - named the Marsili syndrome after their surname - finding that they're hyposensitive to noxious heat, hyposensitive to capsaicin (in chilli peppers) and have experienced pain-free bone fractures. Using DNA from blood samples, the researchers conducted a whole exome sequencing - mapping out the protein-coding genes in the genome of each family member.

 They identified a novel point mutation in the ZFHX2 gene. The mutation alters a part of the gene's protein sequence that is normally consistent across species as variable as mice and frogs. The researchers then conducted two animal studies to understand how the gene affects pain sensations in mice. They initially used mice that had been bred with the ZFHX2 gene entirely absent, and found them to have altered pain thresholds. They then bred a new line of mice that had the relevant mutation, and those mice were notably insensitive to high temperatures.

Further analysis of the mice bearing the mutation clarified that the gene regulates a number of other genes that have previously-established connections to pain signalling. By identifying this mutation and clarifying that it contributes to the family's pain insensitivity, we have opened up a whole new route to drug discovery for pain relief. With more research to understand exactly how the mutation impacts pain sensitivity, and to see what other genes might be involved.
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Cognitive behavioural therapy for chronic pain

Cognitive behavioral therapy CBT offers effective, safer, alternative to opioids for chronic pain treatment. Rising use of opioid medications to treat chronic noncancer pain is a major contributor to opioid crisis. But despite the aggressive marketing and prescribing of these powerful painkillers, there has been little change in the amount and severity of pain.

CBT is an important alternative to opioids for treatment of chronic pain. The goal of CBT is to help patients change the way they think about and manage their pain. The idea is not that pain in the absence of tissue damage is all in your head but rather that all pain is in the head. Cognitive behavioral therapy helps patients understand that pain is a stressor and like other stressors, it is something they can be adapt to and cope with.

Interventions may include relaxation training, scheduling pleasant activities, cognitive restructuring, and guided exercise all in the context of an empathic and validating relationship with the therapist. These interventions have the potential to relieve pain intensity, improve the quality of life, and improve physical and emotional function.

Therapy helps the patient see that emotional and psychological factors influence perception of pain and behaviors that are associated with having pain. Therapy in place cognitive and behavioral strategies help patients to cope more successfully. CBT and other alternative approaches for chronic pain. Studies suggest that CBT has a top-down effect on pain control and perception of painful stimuli.

It can also normalize reductions in the brain's gray matter volume, which are thought to result from the effects of chronic stress. Cognitive behavioral therapy is moderately effective in reducing pain scores, while avoiding or reducing the opioid risks of overuse, addiction, overdose, and death. It can be used as a standalone treatment; in combination with other treatments, including effective non-opioid medications; or as part of efforts to reduce the opioid doses required to control chronic pain.

CBT and other nondrug treatments are underused due to unfamiliarity, time pressure, patient demands, ease of prescribing medications, and low reimbursement rates. There is a need for a paradigm shift from a biomedical to a biopsychosocial model for effective pain treatment and prevention of opioid use disorder.
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Breastfeeding can reduce cesarean section pain

Researchers discovered that mothers who breast-fed their babies for at least 2 months after undergoing a cesarean section (C-section) were less likely to experience pain at the surgical site than those who breast-fed for less than two months.

Dr. Berenjeno and colleagues discovered this by analyzing the data of 185 mothers who underwent a C-section between January 2015 and December 2016.

In the 24 hours after their C-section, the mothers were interviewed about their levels of chronic pain at the surgical site, as well as their breast-feeding practices and the presence of anxiety during breast-feeding.

 Interviews were conducted again within 72 hours of C-section and at 4 months after. Breastfeeding was taken
up by 87 percent of the mothers, and 58 percent of these breast-fed their babies for at least 2 months.

About 11.4 percent of mothers reported experiencing chronic pain after C-section. Researchers discovered that
the rate of chronic pain was higher among mothers who breast-fed for a shorter duration.



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Coffee can replace pain killer drugs

Caffeine intake is as effective as some commonly-used pain killer drugs like ibuprofen in easing pain, according to a recent animal study published in the journal Nature Medicine.

According to researchers at the Boston Children’s Hospital and Beth Israel Deaconess Medical Center, chronic sleep deprivation leads to increased pain sensitivity.

 The research team said that people who suffer from chronic pain may get relief from sleeping more or taking medications that promote wakefulness.

As part of the study, the research team tested the effects of acute or chronic sleep deprivation on mice and measured the animal models’ sleepiness and sensitivity to both painful and non-painful stimuli.

 The scientists also assessed the efficacy of standard pain medications such as ibuprofen and morphine against wakefulness-promoting agents like caffeine and modafinil.

 The research team also used tiny headsets that took electroencephalography and electromyography readings to monitor the animals’ sleeping patterns. In addition, the researchers induced sleep loss in the animals by “entertaining” them.

The researchers also found that participants who drank coffee prior to the sub-maximal exercise test exhibited a 26 percent reduction in pain.