Tag: pain

Categories : Paediatrics Pain ManagementTags :

Newborns Can Sense Pain Before They Can Understand It

On By ModernMedia
Photo by Christian Bowen on Unsplash

Brain networks responsible for sensing, understanding, and responding emotionally to pain develop at different rates in infants, with the conscious understanding of pain not fully developed until after birth, finds a new study led by UCL (University College London) researchers.

The authors of the study, published in the journal Pain, investigated how different types of pain processing develop very early on, by scanning the brains of infants born prematurely.

Lead author Professor Lorenzo Fabrizi (UCL Neuroscience, Physiology & Pharmacology) said: “Pain is a complex experience with physical, emotional, and cognitive elements. In adults, pain processing relies on a functional network of brain regions called the ‘pain connectome’, with different regions working together to help us experience pain, each part responsible for different aspects of it.

“In newborn babies, this network is underdeveloped, which could mean that pain experience in newborns is totally different from the way we, as adults, understand it.”

The scientists, based at UCL, UCLH and King’s College London, were looking at three different components of pain processing: sensory-discriminative (identifying and localising the intensity and quality of pain), affective-motivational (resulting in the emotional response to pain), and cognitive-evaluative (the appraisal and interpretation of pain).

Using advanced brain imaging data from two of the largest available databases of brain magnetic resonance imaging (MRI) in the world – the Developing Human Connectome Project and the Human Connectome Project – the researchers mapped how these networks grow in a group of 372 infants, mostly born preterm, from less than 32 weeks up to 42 weeks after conception. The infants were all less than two weeks old when the scans took place, to ensure that the findings reflected the intrinsic brain maturation, without being affected by different experiences post-birth.

The researchers compared these findings to brain data from adults, as the mature pain-processing networks have previously been mapped out in other studies. The researchers analysed how much the brain networks known to be responsible for processing pain were functionally connected in infants at different ages.

The scientists found that the first subnetwork to reach adult levels in strength and connectivity is the sensory-discriminative network, at around 34-36 weeks after conception, so that babies can sense pain but are not yet fully capable of responding emotionally or interpreting the pain. Before this point, infants may have difficulty identifying what part of their body is experiencing pain. At around 36-38 weeks, the affective-motivational subnetwork reaches maturity, so that infants can identify pain as unpleasant and threatening.

The cognitive-evaluative subnetwork does not reach maturity until more than 42 weeks after conception, meaning that babies born at full term have still not fully developed the brain networks required to understand pain.

The research team had previously found in a 2023 study that preterm babies do not habituate to repeated pain experiences in medically necessary procedures (that is, their reaction to repeated pain does not reduce over time). The new finding that preterm babies have not fully developed the brain connections responsible for appraising pain may help to explain this.

Professor Fabrizi said: “Our results suggest that preterm babies may be particularly vulnerable to painful medical procedures during critical stages of brain development. The findings therefore emphasise the importance of informed paediatric care, including the role of tailored pain management and carefully planned timing of medical interventions for newborns, particularly those born preterm.”

Source: University College London

Categories : GastrointestinalTags :

Pain-sensing Neurons Protect the Gut from Damage

On By ModernMedia
Photo by Andrea Piacquadio on Pexels

Neurons that sense pain protect the gut from inflammation and associated tissue damage by regulating the microbial community living in the intestines, according to a study from Weill Cornell Medicine researchers.

The study, published in Cell, found in a preclinical model that pain-sensing neurons in the gut secrete a molecule called substance P, which appears to protect against gut inflammation and related tissue damage by boosting the population of beneficial microbes in the gut. The researchers also found that these pain-sensing nerves are diminished in number, with significant disruptions to their pain-signaling genes, in people who have inflammatory bowel disease (IBD).

“These findings reshape our thinking about chronic inflammatory disease, and open up a whole new approach to therapeutic intervention,” said study senior author Dr David Artis at Weill Cornell Medicine.

The study’s first author, DrWen Zhang, added: “Defining a previously unknown sensory function for these specific neurons in influencing the microbiota adds a new level of understanding to host-microbiota interactions.”

IBD covers two distinct disorders, Crohn’s disease and ulcerative colitis. It is typically treated with drugs that directly target elements of the immune system. Scientists now appreciate that gut-dwelling bacteria and other microbes also help regulate gut inflammation.

As Dr Artis’s laboratory and others have shown in recent years, the nervous system, which is ‘wired’ into most organs, appears to be yet another powerful regulator of the immune system at the body’s barrier surfaces. In the new study, Dr Artis and his team specifically examined pain neurons that innervate the gut.

These gut-innervating pain neurons, whose cell bodies sit in the lower spine, express a surface protein called TRPV1, which serves as a receptor for pain-related signals. TRPV1 can be activated by high heat, acid, and the chili-pepper compound capsaicin, for example – and the brain translates this activation into a sense of burning pain. The researchers found that silencing these TRPV1 receptors in gut nerves, or deleting TRPV1-expressing neurons, led to much worse inflammation and tissue damage in IBD mouse models, whereas activating the receptors had a protective effect.

The investigators observed that the worsened inflammation and tissue damage in TRPV1-blocked mice were associated with changes in the relative populations of different species of gut bacteria. When this altered bacterial population was transplanted into normal mice, it caused the same worsened susceptibility to inflammation and damage. By contrast, broad-spectrum antibiotic treatment could reverse this susceptibility even in TRPV1-blocked mice. This result demonstrated that TRPV1-expressing nerves protect the gut mainly by helping to maintain a healthy gut microbe population.

The scientists found strong evidence that a large part of this microbe-influencing effect of TRPV1-expressing nerves comes from a molecule the nerves secrete called substance P – which they observed could reverse, on its own, most of the harmful effects of blocking TRPV1. Experiments also suggested that the signaling between neurons and microbes was two-way – some bacterial species could activate TRPV1-expressing nerves to get them to produce more substance P.

To confirm the relevance to humans, the researchers examined gut tissue from IBD patients, and found abnormal TRPV1 and substance P gene activity as well as fewer signs of TRPV1 nerves overall.

“These patients had disrupted pain-sensing nerves, which may have contributed to their chronic inflammation,” Dr Zhang said.

Precisely how substance P exerts its effects on the gut microbe population, and how these microbes “talk back,” are questions that the researchers are now trying to answer in ongoing studies. But the results so far suggest that the next generation of anti-inflammatory drugs for IBD and other disorders could be compounds that target the nervous system.

“A lot of current anti-inflammatory drugs work in only some patients, and pharma companies really haven’t known why,” Dr Artis said. “Maybe it’s because, when it comes to chronic inflammation, we’ve been seeing only some of the picture – and now the rest, including the role of the nervous system, is starting to come into focus.”

Source: Weill Cornell Medicine