Effect of Vinyl Acetate, Glass Fibers Contents, and Buffer Space on EVA's Mechanical Property and Shock Absorption Ability.

OBJECTIVES: The aim of the study was to evaluate the mechanical properties and impact absorption capacity of prototype materials comprising ethylene vinyl acetate (EVA) of different hardness reinforced using different amounts of glass fibers (GFs), considering a buffer space. MATERIALS AND METHODS: Six prototype materials were made by adding E-GFs (5 and 10 wt%) to EVA with vinyl acetate (VA) contents of 9.4 wt% ("hard" or HA) and 27.5 wt% ("soft" or SO). Durometer hardness and tensile strength tests were performed to evaluate the mechanical properties of the materials. Moreover, an impact test was conducted using a customized pendulum impact tester to assess the impact absorption capacity (with or without a buffer space) of the specimens. RESULTS: The mechanical properties of the prototypes, namely, durometer hardness, Young's modulus, and tensile strength, were significantly higher in the HA group than in the SO group, regardless of the presence or added amount of GFs. The addition of GFs, particularly in a large amount (10 wt%), significantly increased these values. In terms of the impact absorption capacity, the original hardness of the EVA material, that is, its VA content, had a more substantial effect than the presence or absence of GFs and the added amount of GFs. Interestingly, the HA specimens with the buffer space exhibited significantly higher impact absorption capacities than the SO specimens. Meanwhile, the SO specimens without the buffer space exhibited significantly higher impact absorption capacities than the HA specimens. Moreover, regardless of the sample material and impact distance, the buffer space significantly improved impact absorption. In particular, with the buffer space, the impact absorption capacity increased with the added amount of GFs. CONCLUSION: The basic mechanical properties, including durometer hardness, Young's modulus, and tensile strength, of the EVA prototype were significantly increased by reducing the amount of VA regardless of the presence or added amount of GFs. Adding GFs, particularly in large amounts, significantly increased the values of aforementioned mechanical properties. Impact absorption was significantly affected by the hardness of the original EVA material and enhanced by the addition of the buffer space. The HA specimen had a high shock absorption capacity with the buffer space, and the SO specimen had a high shock absorption capacity without the buffer space. With the buffer space, impact absorption improved with the amount of added GFs.

Single-Nucleotide Polymorphisms of the PAR2 and IL-17A Genes Are Significantly Associated with Chronic Pain.

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine.

Intracellular cAMP Signaling Pathway via Gs Protein-Coupled Receptor Activation in Rat Primary Cultured Trigeminal Ganglion Cells.

G protein-coupled receptors in trigeminal ganglion (TG) neurons are often associated with sensory mechanisms, including nociception. We have previously reported the expression of P2Y12 receptors, which are Gi protein-coupled receptors, in TG cells. Activating P2Y12 receptors decreased the intracellular free Ca2+ concentration ([Ca2+]i). This indicated that intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels can mediate Ca2+ signaling in TG cells. Here, we report more extensive-expression patterns of Gs protein-coupled receptors in primary cultured TG neurons isolated from 7-day-old newborn Wistar rats and further examine the roles of these receptors in cAMP signaling using the BacMam sensor in these neurons. To identify TG neurons, we also measured [Ca2+]i using fura-2 in TG cells and measured intracellular cAMP levels. TG neurons were positive for Gαs protein-coupled receptors, beta-2 adrenergic (ß2), calcitonin gene-related peptide (CGRP), adenosine A2A (A2A), dopamine 1 (D1), prostaglandin I2 (IP), and 5-hydroxytriptamine 4 (5-HT4) receptor. Application of forskolin (FSK), an activator of adenylyl cyclase, transiently increased intracellular cAMP levels in TG neurons. The application of a phosphodiesterase inhibitor augmented the FSK-elicited intracellular cAMP level increase. These increases were significantly suppressed by the application of SQ22536, an adenylyl cyclase inhibitor, in TG neurons. Application of agonists for ß2, CGRP, A2A, D1-like, IP, and 5-HT4 receptors increased intracellular cAMP levels. These increases were SQ22536-sensitive. These results suggested that TG neurons express ß2, CGRP, A2A, D1, IP, and 5-HT4 receptors, and the activations of these Gαs protein-coupled receptors increase intracellular cAMP levels by activating adenylyl cyclase.

Clinical Application of Inferior Alveolar Nerve Block Device for Safe and Secure IANB by Any Operator.

The inferior alveolar nerve block (IANB) is an established technique with a success rate of 60-80%; however, large errors have been reported among operators. Some dentists do not prefer to use IANB because of the risk of complications. Nevertheless, it is a useful technique for pain control, and a secure IANB offers significant benefits to operators and patients. This case series study aimed to investigate the efficacy of the "IANB Device," a nerve block guide for IANB, and the adverse events associated with its use in clinical practice. IANB was performed using the device on five patients who had undergone detailed computed tomography examination for chronic orofacial pain in the third division of the trigeminal nerve. Lidocaine 1% (1 mL, no adrenaline added) was used as the local anesthetic. IANB was performed by three dentists with 2, 5, and 11 years of experience in orofacial pain treatment. Thus, the data were collected in triplicate for each patient. The primary endpoints were whether adjustment of the IANB device was required, changes in the sensation threshold of the lower lip, the time to disappearance of pain, the presence or absence of tongue sensation ("Do you have numbness in your tongue?": "Yes/No"), and discomfort (visual analog scale). The incidence of any other adverse events was recorded. The procedure was judged to be successful if the pain disappeared and an elevation in the sensation threshold of the lower lip was observed. Adjustment of the IANB device was not required in any patient. A significant elevation in the sensation threshold of the lower lip and the disappearance of pain were observed in all patients. Three of the five patients reported experiencing tongue numbness. Discomfort with the use of the IANB device was less than 30 mm on the visual analog scale. No notable complications were observed. The appropriate type, concentration, and dosage of the local anesthetic must be considered during general dental treatment and oral surgical procedures. Our findings suggest that the IANB device is useful for eliminating errors between operators, enhancing safety, and improving the success rate.

The rs216009 single-nucleotide polymorphism of the CACNA1C gene is associated with phantom tooth pain.

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. The present study focused on the CACNA1C gene, which encodes the α1C subunit of the Cav1.2 L-type Ca2+ channel (LTCC) that has been reported to be associated with neuropathic pain in previous studies. We investigated genetic polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 33 patients with PTP and 118 patients without PTP but with pain or dysesthesia in the orofacial region. From within and around the CACNA1C gene, 155 polymorphisms were selected and analyzed for associations with clinical data. We found that the rs216009 single-nucleotide polymorphism (SNP) of the CACNA1C gene in the recessive model was significantly associated with the vulnerability to PTP. Homozygote carriers of the minor C allele of rs216009 had a higher rate of PTP. Nociceptive transmission in neuropathic pain has been reported to involve Ca2+ influx from LTCCs, and the rs216009 polymorphism may be involved in CACNA1C expression, which regulates intracellular Ca2+ levels, leading to the vulnerability to PTP. Furthermore, psychological factors may lead to the development of PTP by modulating the descending pain inhibitory system. Altogether, homozygous C-allele carriers of the rs216009 SNP were more likely to be vulnerable to PTP, possibly through the regulation of intracellular Ca2+ levels and affective pain systems, such as those that mediate fear memory recall.

Improvement in persistent idiopathic facial pain with comorbid ADHD using the combination of a dopamine system stabilizer and psychostimulant: A case report.

Key Clinical Message: Persistent idiopathic facial pain (PIFP) and attention-deficit/hyperactivity disorder (ADHD) may coexist and can be improved with ADHD medications. Thus, clinicians should screen for ADHD by a multidisciplinary approach when treating PIFP and differentiate between other odontogenic disorders. Abstract: We report a case of a woman with persistent idiopathic facial pain (PIFP) and attention-deficit/hyperactivity disorder (ADHD) that markedly improved with the administration of a combination of aripiprazole (APZ) and methylphenidate (MP) treatment. Screening for ADHD and administration of APZ and/or MP may be considered in treating PIFP.

Effects of Myostatin on Nuclear Morphology at the Myotendinous Junction.

Myostatin (Myo) is known to suppress skeletal muscle growth, and was recently reported to control tendon homeostasis. The purpose of the present study was to investigate the regulatory involvement of Myo in the myotendinous junction (MTJ) in vivo and in vitro. After Achilles tendon injury in mice, we identified unexpected cell accumulation on the tendon side of the MTJ. At postoperative day 7 (POD7), the nuclei had an egg-like profile, whereas at POD28 they were spindle-shaped. The aspect ratio of nuclei on the tendon side of the MTJ differed significantly between POD7 and POD28 (p = 4.67 × 10-34). We then investigated Myo expression in the injured Achilles tendon. At the MTJ, Myo expression was significantly increased at POD28 relative to POD7 (p = 0.0309). To investigate the action of Myo in vitro, we then prepared laminated sheets of myoblasts (C2C12) and fibroblasts (NIH3T3) (a pseudo MTJ model). Myo did not affect the expression of Pax7 and desmin (markers of muscle development), scleraxis and temonodulin (markers of tendon development), or Sox9 (a common marker of muscle and tendon development) in the cell sheets. However, Myo changed the nuclear morphology of scleraxis-positive cells arrayed at the boundary between the myoblast sheet and the fibroblast sheet (aspect ratio of the cell nuclei, myostatin(+) vs. myostatin(-): p = 0.000134). Myo may strengthen the connection at the MTJ in the initial stages of growth and wound healing.

Genetic Polymorphisms of ENPP2 Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study.

Autotaxin, encoded by the ENPP2 gene, is a known key element of neuropathic pain; however, its involvement in nociceptive pain processing remains unclear. We explored the associations between postoperative pain intensity, 24-h postoperative opioid dose requirements, and 93 ENNP2-gene single-nucleotide polymorphisms (SNPs) in 362 healthy patients who underwent cosmetic surgery using the dominant, recessive, and genotypic models. Next, we validated the associations between relevant SNPs on the one hand and pain intensity and daily opioid dosages on the other in 89 patients with cancer-related pain. In this validation study, a Bonferroni correction for multiplicity was applied on all relevant SNPs of the ENPP2 gene and their respective models. In the exploratory study, three models of two SNPs (rs7832704 and rs2249015) were significantly associated with postoperative opioid doses, although the postoperative pain intensity was comparable. In the validation study, the three models of the two SNPs were also significantly associated with cancer pain intensity (p < 0.017). Patients with a minor allele homozygosity complained of more severe pain compared with patients with other genotypes when using comparable daily opioid doses. Our findings might suggest that autotaxin is associated with nociceptive pain processing and the regulation of opioid requirements.

Head injuries caused by contact with teeth during sports and exercise activities in Japanese schools during the period 2012-2018.

BACKGROUND/AIM: During sports activities, teeth-related contact can cause injury to both ally and opponent players, which can lead to potential infections and aesthetic problems. However, the extent of such injuries remains unclear. This study aimed to clarify the frequency and situation of head injuries caused by teeth (HICBT) occurring under the supervision of schools in Japan. MATERIAL AND METHODS: HICBT records were extracted from the Japan Sport Council data on head injuries occurring reported during the 7-year period from 2012 to 2018 under the supervision of schools in Japan. RESULTS: Of the total 463,527 head injury cases during the study period, 4495 cases (approximately 1%) were HICBT. Of the HICBT cases, 3650 (81.20%) were related to sports and athletic activity. Such injuries were reported to occur most often during basketball with a rate of 57.07% and 50.43%; soccer/futsal was the next most common sport with a rate of 13.38% and 24.01% in junior high school and high school students. Tag games were responsible for a similar number of HICBT cases at 22.73% and 39.03% in kindergartens and elementary school students. CONCLUSIONS: A total of 4495 cases of HICBT were identified, accounting for about 1% of all head injuries under the supervision of schools in Japan during the study period. This result reminds us that our teeth could be the weapon against the players during sports events. HICBTs occurring during basketball and soccer/futsal, in which mouthguards are not mandatory, were conspicuous among junior and senior high school students. Active use of mouthguards in various sports will protect players as well as their teammates and opponents. Sports dentists should encourage the revision of rules, such as mandating the use of mouthguards, in popular sports with a high incidence of HICBT, such as basketball and soccer/futsal.

Diagnosis and treatment of intractable idiopathic orofacial pain with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with primary chronic pain syndromes, such as fibromyalgia, migraine, and chronic low back pain. Although idiopathic orofacial pain (IOP) is classified as burning mouth syndrome or persistent idiopathic facial or dentoalveolar pain and as a primary chronic pain, the association between IOP and ADHD has not been investigated. This retrospective cohort study investigated the severity of ADHD symptoms measured using the ADHD scale and the effects of treatment using ADHD drugs and the dopamine system stabilizer aripiprazole. The participants were 25 consecutive patients with refractory IOP referred to a psychiatrist and diagnosed with coexisting ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5. The ADHD scale scores were higher in patients with intractable IOP than those in the general population. Pharmacotherapy used in this study led to clinically significant improvements in pain, anxiety/depression, and pain catastrophizing. Intractable IOP and ADHD were shown to be associated. In the future, screening and pharmacotherapy for ADHD should be considered in the treatment of intractable IOP.

Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Improving light-cured intermediate resin for hard and space mouthguard using a glass fiber.

BACKGROUND/AIMS: A light-cured intermediate material is useful for fabricating a hard insert and a buffer space mouthguard (H&SMG). However, it requires improvement in its mechanical properties and shock-absorbing capacity. The aim of this study was to evaluate the mechanical properties of two prototype light-cured intermediate materials reinforced with glass fibers, and the impact absorption capacity and durability of H&SMGs made with the prototype intermediate materials. MATERIALS AND METHODS: Two prototype materials containing long and microlength glass fibers in a light-cured intermediate material, Innerframe LC®, for H&SMG, were fabricated and tested. A three-point bending test was performed for evaluation of the mechanical properties. In addition, a shock absorption test was conducted using a customized pendulum impact testing machine to evaluate the H&SMGs' impact absorption capacity and durability. RESULTS: Long and microlength glass fibers significantly improved flexural modulus and strength. H&SMGs made with these two glass fiber-containing materials had high impact absorption capacity against both low and high impact forces, while the mouthguards made with long glass fiber materials had the best results. CONCLUSION: Long and microlength glass fibers with the prototype materials improved the mechanical properties of Innerframe LC® and the impact absorption capacity and durability of H&SMGs. H&SMGs made with the long glass fiber prototype materials had the best performance.

Effects of Mouthguards on Skin Damage In Vitro Study.

OBJECTIVE: Mouthguards can prevent and reduce orofacial sports traumas, which occur to the players themselves. However, the effect of mouthguards on skin damage has not been clarified. The present study's purpose was to examine whether the mouthguard can reduce or prevent skin damage caused by teeth (including the difference in mouthguard thickness). MATERIALS AND METHODS: Pigskins, artificial teeth, and Ethylene-vinyl acetate (EVA) mouthguard blanks with 1.5- and 3.0-mm thickness were employed. Each of the two type mouthguards was produced in 10 replicates. Mouthguard incisal thickness and collision touch angle were measured on a PC using imaging software. A pendulum-type machine was used to apply impact. Strain gauges attached to the tooth and impacted plate were used to measure mouthguards' effect on impact stress. Also, a microscope was used to observe the after impacted skin condition, and the extent of damage was assessed as a score. RESULTS: The pigskin was ruptured in without mouthguard (NOMG) with presenting the highest damage score, whereas the complete rupture was not seen in the 1.5 mm MG, but the damage of the skin (defeat) was observed. No tissue change was found with the 3 mmMG. In both the flat plate and impact tooth strain, no significant difference was observed between NOMG and 1.5 mmMG. However, 3 mmMG had a significantly smaller value than the other two conditions. These results are likely to be strongly influenced by the mouthguard incisal thicknesses and collision touch angles differences. CONCLUSION: The present study results clarified that two different thickness mouthguards reduced the skin damage, and the thicker mouthguard showed more effectiveness. Therefore, mouthguards may prevent the wearer's stomatognathic system's trauma and avoid damage to the skin of other athletes they are playing with. This effect seems to be an essential basis for explaining the necessity of using mouthguards for others besides full-contact sports.

Jaw-Clenching Intensity Effects on Masseter Oxygen Dynamics and Fatigue: A NIRS Oximetry Study.

The purpose of this study was to clarify the effects of jaw-clenching intensity on masseter muscle oxygen dynamics during clenching and recovery and masseter muscle fatigue using the spatially resolved method of near-infrared spectroscopy. Pulse rate, mean power frequency from electromyography in the masseter and visual analogue scale for masseter fatigue were also examined as related items. The 25% and 50% maximum voluntary contractions were determined using electromyography before the experiment and used as visual feedback on the screen. Twenty-three healthy adult male subjects volunteered for this study. Clenching decreased oxygen and oxygenated haemoglobin, and increased deoxygenated haemoglobin in the masseter muscle. The higher the intensity of clenching, the more prominent the effect. The oxygen dynamics tended to return to normal after clenching, but the change was slower with higher clenching intensity. Pulse rate increased with clenching, and the increment was more prominent with higher clenching intensity. Clenching caused a shift of mean power frequency to a lower range, an increase in subjective fatigue, an early appearance of a breakpoint appearance time and a prolongation of a 1/2 recovery time. All of these effects were more evident with increasing clenching intensity. In conclusion, clenching intensity influenced the oxygen dynamics of the masseter muscle and fatigue state during clenching and recovery. The higher the intensity, the greater the impact.

Neurometabolite Levels and Relevance to Central Sensitization in Chronic Orofacial Pain Patients: A Magnetic Resonance Spectroscopy Study.

Background: Refractory chronic pain in the orofacial region involves central sensitization (CS). However, not all chronic pain patients exhibit CS. An objective assessment of CS may be useful for pain management. Changes in the balance of excitatory and inhibitory neural activity or excessive activity of nerves and glial cells may cause CS and contribute to pain chronification. Patients and Methods: 1H-magnetic resonance spectra were acquired from the anterior cingulate cortex (ACC) and thalamus in 20 patients with chronic orofacial pain and suspected CS, and 21 healthy volunteers, using a single-voxel point-resolved spectroscopy sequence. The patients were assessed using the Central Sensitization Inventory. Results: Aspartate/total creatine (tCr) and glutathione in the ACC were significantly higher in the patient group. However, no significant difference was observed between groups in the neurometabolites measured in the thalamus. Patients also exhibited a tendency for increased gamma-aminobutyric acid (GABA)/tCr in the ACC. There were positive relationships between Central Sensitization Inventory scores and glutamate + glutamine (Glx) in the thalamus, a positive trend for Glx in the ACC and a negative relationship for GABA/tCr in the ACC. Conclusion: The high levels of aspartate/tCr and glutathione in the patient group suggest excitatory neuronal activity and hyperactivity of neurons and glial cells. The correlation analysis results suggest that excitatory and inhibitory neurometabolites are involved in the chronification of orofacial pain, including CS.

Clinical Statistics of Dysphagia Rehabilitation Provided on Dental Visits to a Partner Hospital.

Maintaining oral hygiene is an important yet often neglected aspect of rehabilitation medicine. Our visiting dental team, which provides dental treatments and swallowing rehabilitation, partnered with a medical hospital that had no dental department and began visiting and treating inpatients at this hospital. This study is aimed at evaluating the effects of dysphagia rehabilitation, and this was jointly conducted by medical and dental hospitals. The survey was conducted between May 2017 and March 2018. We retrospectively examined dysphagia rehabilitation provided to 25 patients (12 men and 13 women) aged 40-92 years (mean age: 77.1 ± 12.3 years). The largest number of requests for dental treatment was received from the internal medicine department (13 requests, 52.0%). A total of 39 videofluoroscopic or videoendoscopic examinations of swallowing interventions for dysphagia rehabilitation were conducted. All patients' oral and swallowing functions were evaluated using the functional oral intake scale (FOIS). At initial assessment, 9, 13, and 0 patients were at FOIS levels 1, 2, and 3 (use of tube feeding), respectively, and 1, 2, and 0 patients were at FOIS levels 4, 5, and 6 (only oral feeding), respectively. At the final assessment, 6, 10, and 4 patients were at FOIS levels 1, 2, and 3, respectively, and 0, 2, and 3 patients were at FOIS levels 4, 5, and 6, respectively. Oral and swallowing functions differed significantly between the first and final visits (p = 0.02). Visits conducted by a team of oral health practitioners to a medical hospital without a dental department appear to have a major impact and will become even more important in the future.

Associations between the C3orf20 rs12496846 Polymorphism and Both Postoperative Analgesia after Orthognathic and Abdominal Surgeries and C3orf20 Gene Expression in the Brain.

Considerable individual differences are widely observed in the sensitivity to opioid analgesics. We focused on rs12496846, rs698705, and rs10052295 single-nucleotide polymorphisms (SNPs) in the C3orf20, SLC8A2, and CTNND2 gene regions that we previously identified as possibly associated with postoperative analgesia after orthognathic surgery. We investigated associations between these SNPs and postoperative analgesia in 112 patients who underwent major open abdominal surgery in hospitals and were treated with analgesics, including opioids, after surgery. Total genomic DNA was extracted from peripheral blood or oral mucosa samples for genotyping each SNP. Effects of these potent SNPs on gene expression in the brain were also investigated in samples that were provided by the Stanley Foundation Brain Bank. In the association studies, carriers of the G allele of the rs12496846 SNP in the C3orf20 gene region were significantly associated with greater 24 h postoperative analgesic requirements among the three SNPs that were investigated (p = 0.0015), which corroborated a previous study of orthognathic patients (p < 0.0001). In the gene expression analysis, carriers of the G allele of the rs12496846 SNP were significantly associated with lower mRNA expression of the C3orf20 gene (p < 0.0001). These results indicate that this SNP could serve as a marker that predicts analgesic requirements.

Short Tandem Repeat Variation in the CNR1 Gene Associated With Analgesic Requirements of Opioids in Postoperative Pain Management.

Short tandem repeats (STRs) and variable number of tandem repeats (VNTRs) that have been identified at approximately 0.7 and 0.5 million loci in the human genome, respectively, are highly multi-allelic variations rather than single-nucleotide polymorphisms. The number of repeats of more than a few thousand STRs was associated with the expression of nearby genes, indicating that STRs are influential genetic variations in human traits. Analgesics act on the central nervous system via their intrinsic receptors to produce analgesic effects. In the present study, we focused on STRs and VNTRs in the CNR1, GRIN2A, PENK, and PDYN genes and analyzed two peripheral pain sensation-related traits and seven analgesia-related traits in postoperative pain management. A total of 192 volunteers who underwent the peripheral pain sensation tests and 139 and 252 patients who underwent open abdominal and orthognathic cosmetic surgeries, respectively, were included in the study. None of the four STRs or VNTRs were associated with peripheral pain sensation. Short tandem repeats in the CNR1, GRIN2A, and PENK genes were associated with the frequency of fentanyl use, fentanyl dose, and visual analog scale pain scores 3 h after orthognathic cosmetic surgery (Spearman's rank correlation coefficient ρ = 0.199, p = 0.002, ρ = 0.174, p = 0.006, and ρ = 0.135, p = 0.033, respectively), analgesic dose, including epidural analgesics after open abdominal surgery (ρ = -0.200, p = 0.018), and visual analog scale pain scores 24 h after orthognathic cosmetic surgery (ρ = 0.143, p = 0.023), respectively. The associations between STRs in the CNR1 gene and the frequency of fentanyl use and fentanyl dose after orthognathic cosmetic surgery were confirmed by Holm's multiple-testing correction. These findings indicate that STRs in the CNR1 gene influence analgesia in the orofacial region.

Single-nucleotide polymorphisms of the SLC17A9 and P2RY12 genes are significantly associated with phantom tooth pain.

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. We focused on solute carrier family 17 member 9 (SLC17A9)/vesicular nucleotide transporter (VNUT) and purinergic receptor P2Y12 (P2RY12), both of which have been associated with neuropathic pain and pain transduction signaling in the trigeminal ganglion in rodents. We sought to corroborate these associations in humans. We investigated gene polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 150 patients with orofacial pain, including PTP, and 500 healthy subjects. We found that the rs735055 polymorphism of the SLC17A9 gene and rs3732759 polymorphism of the P2RY12 gene were associated with the development of PTP. Carriers of the minor allele of rs735055 and individuals who were homozygous for the major allele of rs3732759 had a higher rate of PTP. Carriers of the minor allele of rs735055 reportedly had high SLC17A9 mRNA expression in the spinal cord, which may increase the storage and release of adenosine triphosphate. Individuals who were homozygous for the major allele of rs3732759 may have higher P2RY12 expression that is more active in microglia. Therefore, these carriers may be more susceptible to PTP. These results suggest that specific genetic polymorphisms of the SLC17A9 and P2RY12 genes are involved in PTP. This is the first report on genes that are associated with PTP in humans.