New research published in the journal Headache reveals that, in children and adolescents, pain in the lower limbs – what are often called “growing pains” by clinicians and are commonly attributed to rapid growth – may indicate the presence or risk of migraines.
The study included 100 children and adolescents born to mothers with migraines seen at a headache clinic, with half of the youth experiencing growing pains.
“In families of children with growing pains, there is an increased prevalence of other pain syndromes, especially migraine among parents,” the authors wrote. “On the other hand, children with migraine have a higher prevalence of growing pains, suggesting a common pathogenesis; therefore, we hypothesised that growing pains in children are a precursor or comorbidity with migraine.”
After five years of follow-up, 78 patients completed the study, of which 42 were from the group that experienced growing pains and 36 were from the control group. Headaches occurred in 76% of participants who had growing pains and in 22% of controls. Growing pains persisted in 14% of participants who had growing pains at the start of the study and appeared in 39% of participants who were previously asymptomatic.
“Pain in the lower limbs of children and adolescents… may reflect a precursor or comorbidity with migraine,” the authors concluded.
It has been believed speed of information transmitted among regions of the brain stabilised during early adolescence. A study in Nature Neuroscience has instead found that transmission speeds continue to increase into early adulthood, which may explain the emergence of mental health problems over this period. In fact, transmission speeds increase until around age 40, reaching a speed twice that of a 4-year old child.
As mental health problems such as anxiety, depression and bipolar disorders can emerge in late adolescence and early adulthood, a better understanding of brain development may lead to new treatments.
“A fundamental understanding of the developmental trajectory of brain circuitry may help identify sensitive periods of development when doctors could offer therapies to their patients,” says senior author Dora Hermes, PhD, a biomedical engineer at Mayo Clinic.
Called the human connectome, the structural system of neural pathways in the brain or nervous system develops as people age. But how structural changes affect the speed of neuronal signalling has not been well described.
“Just as transit time for a truck would depend on the structure of the road, so does the transmission speed of signals among brain areas depend on the structure of neural pathways,” Dr Hermes explains. “The human connectome matures during development and aging, and can be affected by disease. All these processes may affect the speed of information flow in the brain.” In the study, Dr Hermes and colleagues stimulated pairs of electrodes with a brief electrical pulse to measure the time it took signals to travel among brain regions in 74 research participants between the ages of 4 and 51. The intracranial measurements were done in a small population of patients who had electrodes implanted for epilepsy monitoring at University Medical Center Utrecht, Netherlands.
The response delays in connected brain regions showed that transmission speeds in the human brain increase throughout childhood and even into early adulthood. They plateau around 30 to 40 years of age.
The team’s data indicate that adult transmission speeds were about two times faster compared to those typically found in children. Transmission speeds also were typically faster in 30- or 40-year-old subjects compared to teenagers.
Brain transmission speed is measured in milliseconds, a unit of time equal to one-thousandth of a second. For example, the researchers measured the neuronal speed of a 4-year-old patient at 45 milliseconds for a signal to travel from the frontal to parietal regions of the brain. In a 38-year-old patient, the same pathway was measured at 20 milliseconds. For comparison, the blink of an eye takes about 100 to 400 milliseconds.
The researchers are working to characterise electrical stimulation-driven connectivity in the human brain. One of the next steps is to better understand how transmission speeds change with neurological diseases. They are collaborating with paediatric neurosurgeons and neurologists to understand how diseases change transmission speeds compared to what would be considered within the normal range for a certain age group.
The phrase ‘growing pains’ is often used by people to describe muscle or joint pain in young people and health professionals also use the term. However a broad review of medical literature has found there is no consistent medical definition of the condition behind a diagnosis.
Researchers from the University of Sydney found there is no agreement in the literature on what growing pains really are, what they mean, how they are defined, and how they should be diagnosed.
Growing pains may be a medical misnomer, the researchers said – more than 93% of studies did not refer to growth when defining the condition. Similarly, age was not mentioned in more than 80% of studies’ definitions.
The findings have prompted the researchers to recommend the term growing pains not be used by clinicians and other researchers as a stand-alone diagnosis, until a clear definition backed by evidence has been established.
Growing pains are considered to be one of the most common causes of recurring musculoskeletal pain in children and adolescents. Some studies suggest up to a third of children experience the condition at some point in their life.
The term first arose in 1823 in a book called ‘Maladies de la Croissance’ (‘diseases of growth’).
“Thousands of kids are diagnosed with growing pains by their healthcare professional, but we were curious – what does that diagnosis really mean?” said lead author Dr Mary O’Keeffe from Institute for Musculoskeletal Health at the University of Sydney.
In order to see how researchers defined the term, and if there were any detailed criteria that led to a diagnosis, the reviewers examined 147 studies that mentioned growing pains. The medical literature spanned many types of research, including systematic reviews, editorials, observational studies, case-control studies, and theses.
“What we found was a little concerning: that there is no consistency in the literature on what ‘growing pains’ means,” said Professor Steven Kamper, at the University of Sydney.
“The definitions were really variable, vague and often contradictory. Some studies suggested growing pains happened in the arms, or in the lower body. Some said it was about muscles while other studies said joints.”
Only seven studies, less than 10% of the studies examined, mentioned growth related to the pain. More than 80% of the studies did not mention a young person’s age at the time ‘growing pains’ occurred.
There was no widespread agreement or detail on where the pain was located or when the pain happened.
Half of the studies referenced ‘growing pains’ as being located in the lower limb, while 28% reported specifically in the knees.
As for time of occurrence, 48% of studies reported the ‘growing pains’ happens during the evening or night and 42% reported it was recurring.
“What this study uncovered was while ‘growing pains’ is a very popular label used to diagnose musculoskeletal pain, it means very different things to different people,” said senior author Professor Steve Kamper.
“This level of uncertainty means clinicians don’t have a clear guide or criteria to know when the label ‘growing pains might be appropriate for a patient’.”
The study questioned whether growing pains are connected to growth itself in bone or muscle.
“There is a lack of evidence or inconsistent information on growing pains as a condition – and how it is associated with growth, or even the cause of the pain,” said Dr O’Keeffe.
“There is a real opportunity to understand this condition – given how widespread the use of the term is, or whether there is even a need to use this term.”
A new study shows that sex hormones are important for developing gender role behaviours in boys, such as active play.
In laboratory animals, sex differences in behaviour arise from different hormone levels produced by males and females influence patterns of gene expression in the developing brain. However, the origins of sex differences in human behaviour are not as well understood.
“In the lab, you can do experiments on how these hormones affect animal brains and perform other experimental manipulations. We can’t do those things to people, so we looked to a natural experiment,” explained study leader David Puts, associate professor of anthropology.
Prof Puts and his collaborators made use of a natural experiment called isolated GnRH deficiency (IGD), a rare endocrine disorder. Individuals with IGD lack sex hormones from the second trimester of development right through until they begin hormone replacement therapy to induce puberty. However, as the external genitals develop earlier, during the first trimester, people with IGD are clearly male or female at birth, and are raised according to their sex.
IGD therefore presents the chance to study the behaviour of those raised as boys but exposed to low testicular hormones, or raised as girls but exposed to low ovarian hormones.
The researchers compared 97 individuals with IGD (a small number due to its rarity) to 1665 individuals with typical hormonal development. Differences in behaviour were investigated; boys being encouraged toward active play, girls pushed to more passive pursuits. The researchers asked subjects to recall behaviours they had as children.
“We asked them, ‘When you read a book, were you the male or female in the story?’, ‘Where your friends boys or girls?’, ‘Did you play with dolls or trucks?’,” said Talia N Shirazi, doctoral recipient in anthropology now working in the reproductive health industry.
These childhood gender role behaviours are among the largest differences in behaviour between sexes, Prof Puts said. Typically, males will say they were the male character, played with other boys and preferred trucks, while females will say they were the female character, played with other girls and preferred dolls.
However, males with IGD reported more gender non-conforming in this regard. The researchers found in that men with IGD recalled a higher level of childhood gender non-conformity than typical men, while women with IGD did not differ from typical women in childhood gender conformity.
‘”We don’t see this effect in the women with IGD,” said Shirazi, indicating that low levels of ovarian hormones does not significantly impact childhood gender role behaviours.
“Our results suggest that in humans, androgens, such as testosterone produced by the testes, influence male brain development directly as they do in other mammals, rather than only indirectly by influencing external appearance and consequently gender socialisation,” said Prof Puts. “Both the direct influence of androgens on the developing brain and gender socialisation probably play important roles in producing sex differences in childhood behaviour.”
Prof Puts and Shirazi agree that despite their modest sample of participants with IGD, they are encouraged that the results were very similar in subjects who came from a clinical setting and those recruited from support groups.
“It would be nice to be able to identify people with IGD when they are younger, before they reach what should be puberty,” said Shirazi. “We need to focus on recruitment for our studies because there is a lot that can be learned about the cause of gender behaviours.”
