Impressions

Music Evoking Emotional Responses May Reduce Pain

Researchers say our favorite tunes can be powerful painkillers, and some studies have suggested the effect may occur even in babies.

Now, a research team from McGill University in Montreal, Canada has found evidence that emotional responses generated by music also matter. The study was published in the journal Frontiers in Pain Research.

“We can approximate that favorite music reduced pain by about one point on a 10-point scale, which is at least as strong as an over-the-counter painkiller like [ibuprofen] under the same conditions. Moving music may have an even stronger effect,” said Darius Valevicius, a PhD student and first author of the study.

Valevicius and colleagues asked 63 healthy participants to attend the Roy Pain Lab on the McGill campus, where they used a probe device to heat an area on their left arm – a sensation akin to a hot cup of coffee being held against the skin. While undergoing the process, the participants either listened to two of their favorite tracks, relaxing music selected for them, scrambled music or silence. As the music, sound or silence continued, the participants were asked to rate the intensity and unpleasantness of the pain.

Each participant experienced each condition for around seven minutes and a total of eight pain stimulations and eight ratings.

When the auditory period ended, participants were asked to rate the music’s pleasantness, their emotional arousal, and the number of “chills” they experienced. Chills are a phenomenon linked to sudden emotions or heightened attention that can be felt as tingling, shivers or goosebumps.

The results revealed participants rated the pain less intense by about four points on a 100-point scale, and less unpleasant by about nine points, when listening to their favorite tracks compared with silence or scrambled sound. Relaxing music selected for them did not produce the same effect.

“We found a very strong correlation between music pleasantness and pain unpleasantness, but zero correlation between music pleasantness and pain intensity, which would be an unlikely finding if it was just placebo or expectation effects,” Valevicius said.

Further work revealed that music that produced more chills was associated with lower pain intensity and pain unpleasantness, with lower scores for the latter also associated with music rated more pleasant.

“The difference in effect on pain intensity implies two mechanisms – chills may have a physiological sensory-gating effect, blocking ascending pain signals, while pleasantness may affect the emotional value of pain without affecting the sensation, so more at a cognitive-emotional level involving prefrontal brain areas,” said Valevicius, although he cautioned more work is needed to test these ideas.

Study Finds Viking Dentistry Surprisingly Sophisticated

A study of Viking Age teeth conducted by researchers at the University of Gothenburg in Sweden found widespread caries and toothache as well as surprisingly advanced dentistry, including dental work and filing of front teeth.– and also some dental work and filing of front teeth.

The study examined 3,293 teeth from 171 individuals among the Viking Age population of Varnhem in Västergötland, Sweden. The site is known for extensive excavations of Viking and medieval environments, including tombs where skeletons and teeth have been preserved well in favorable soil conditions.

The research team from the university’s Institute of Odontology worked with an osteologist from the Västergötland museum. The skulls and teeth were transported to Gothenburg, where all the examinations were carried out.

The teeth underwent clinical examinations using standard dentistry tools under bright light. A number of X-ray examinations were also performed using the same technique used in dentistry, where the patient bites down on a small square imaging plate in the mouth.

The results, which were published in the journal PLOS ONE, showed that 49% of the Viking population had one or more caries lesions. Of the adult teeth, 13% were affected by caries – often at the roots. However, children with milk teeth – or with both milk and adult teeth – were entirely caries-free.

Tooth loss was also common among adults. The studied adults had lost an average of 6% of their teeth, excluding wisdom teeth, over their lifetimes. The risk of tooth loss increased with age.

The findings suggest that caries, tooth infections, and toothache were common among the Viking population in Varnhem. However, the study also reveals examples of attempts to look after teeth in various ways.

“There were several signs that the Vikings had modified their teeth, including evidence of using toothpicks, filing front teeth, and even dental treatment of teeth with infections,” says Carolina Bertilsson, DDS, the study’s corresponding author.

One sign of more sophisticated procedures was molars with filed holes, from the crown of the tooth and into the pulp, probably to relieve pressure and alleviate severe toothache due to infection. The filed front teeth may have been a form of identity marker, as the cases found in both this and previous studies were male.

Oral Infections Predict Changes in Metabolic Profiles

Common oral infections, periodontal diseases and caries are associated with inflammatory metabolic profiles related to an increased risk of cardiometabolic diseases, according to a new study by an international team of researchers, which also found that oral infections can predict future adverse changes in metabolic profiles.

The study, conducted by Finnish Health 2000/2011 and published in the Journal of Dental Research, comprised 452 middle-aged and elderly patients and 6,229 participants of the population-based Health-2000 survey. In 2011, 4,116 Health-2000 participants provided a follow-up serum sample. Serum concentrations of 157 metabolites reflecting the risk of chronic diseases, such as lipid and glucose metabolites, ketone bodies and amino acids, were determined with an NMR spectroscopy method.

Parameters describing the oral health status were collected at baseline in clinical and radiographic examinations. The parameters included those describing the periodontal status, such as bleeding on probing, periodontal probing depth and alveolar bone loss. Caries-related parameters included root canal fillings, apical rarefactions and caries lesions. The study was composed of a cross-sectional part analyzing the association between the metabolic measures with prevalent oral health and of prospective part examining whether oral infections predict the levels of metabolic measures in the follow-up.

Among 157 metabolic measures, increased periodontal probing depth associated with 93, bleeding on probing with 88, and periodontal inflammation burden with 77 measures. Among the caries-related parameters, root canal fillings were associated with 47, inadequate root canal fillings with 27, and caries lesions with eight metabolic measures. In the prospective analyses, caries was associated with 30 and bleeding on probing with eight metabolites. These metabolic measures were typical of inflammation, thus showing positive associations with fatty acid saturation degree and very low density lipoprotein (VLDL) parameters and negative associations with high-density lipoprotein (HDL) parameters.

“Oral infections may partially explain unhealthy lipid profiles,” said Aino Salminen, PhD, from the University of Helsinki.

New Compound Outperforms Pain Drug Gabapentin

A compound-one of 27 million screened in a library of potential new drugs – reversed four types of chronic pain in animal studies, according to new research led by NYU College of Dentistry’s Pain Research Center and published in the Proceedings of the National Academy of Sciences (PNAS).

The small molecule, which binds to an inner region of a calcium channel to indirectly regulate it, outperformed gabapentin without troublesome side effects, providing a promising candidate for treating pain.

Calcium channels play a central role in pain signaling, in part through the release of neurotransmitters such as glutamate and GABA – “the currency of the pain signal,” according to Rajesh Khanna, PhD, director of the NYU Pain Research Center and professor of molecular pathobiology at NYU Dentistry. The Cav2.2 (or N-type) calcium channel is the target for three clinically available drugs, including gabapentin (sold under brand names including Neurontin) and pregabalin (Lyrica), which are widely used to treat nerve pain and epilepsy.

Gabapentin mitigates pain by binding to the outside of the Cav2.2 calcium channel, affecting the channel’s activity. However, like many pain medications, gabapentin use often comes with side effects.

“Developing effective pain management with minimal side effects is crucial, but creating new therapies has been challenging,” said Dr. Khanna, senior author of the PNAS study. “Rather than directly going after known targets for pain relief, our lab is focused on indirectly targeting proteins that are involved in pain.”

Dr. Khanna has long been interested in a protein called CRMP2, a key regulator of the Cav2.2 calcium channel that binds to the channel from the inside. He and his colleagues previously discovered a peptide (a small region of amino acids) derived from CRMP2 that could uncouple CRMP2 from the calcium channel. When this peptide – dubbed the calcium channel‐binding domain 3, or CBD3—was delivered to cells, it acted as a decoy, blocking CRMP2 from binding to the inside of the calcium channel. This resulted in less calcium entering the calcium channel and less neurotransmitter release, which translated to less pain in animal studies.

Peptides are difficult to synthesize as drugs because they are short-acting and easily degrade in the stomach, so the researchers sought to create a small molecule drug based on CBD3. Starting with the 15 amino acids that make up the CBD3 peptide, they homed in on two amino acids that studies showed were responsible for inhibiting calcium influx and mitigating pain.

“At that point, we realized that these two amino acids could be the building blocks for designing a small molecule,” said Dr. Khanna.

In collaboration with colleagues at the University of Pittsburgh, the researchers ran a computer simulation that screened a library of 27 million compounds to look for a small molecule that would “match” the CBD3 amino acids. The simulation narrowed the library down to 77 compounds, which the researchers experimentally tested to see if they lessened the amount of calcium influx. This further pared the pool down to nine compounds, which were assessed using electrophysiology to measure decreases in electrical currents through the calcium channels.

One compound, which the researchers named CBD3063, emerged as the most promising candidate for treating pain. Biochemical tests revealed that CBD3063 disrupted the interaction between the CaV2.2 calcium channel and CRMP2 protein, reduced calcium entering the channel, and lessened the release of neurotransmitters.

Dr. Khanna’s lab then tested CBD3063 with mouse models for pain related to injury. The compound was effective in alleviating pain in both male and female mice – and notably, in a head-to-head test with the drug gabapentin, the researchers needed to use far less CBD3063 (1 mg to 10 mg) than gabapentin (30 mg) to reduce pain.

“Many scientists have screened the same library of compounds but have been trying to block the calcium channel from the outside. Our target, these two amino acids from CRMP2, is on the inside of the cell, and this indirect approach may be the key to our success,” said Dr. Khanna.