Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects.

BACKGROUND: Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS: We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS: SNP rs4680 (val158 met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5' regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations.

Exercise induced hypoalgesia profile in rats is associated with IL-10 and IL-1 ß levels and pain severity following nerve injury.

BACKGROUND: Pain may undergo modulation in the central nervous system prior to reaching the primary somatosensory cortex and being perceived as pain. Faulty pain modulation mechanisms have been linked to various chronic pain conditions. Cytokines such as IL-10 and IL-1beta, are known to be involved in initiation and maintenance of neuropathic pain. In this study, we investigated the association between pain modulation profile, pain intensity and cytokines (IL-10 and IL-1beta) levels in a rat model of neuropathic pain. METHODS: Exercise-Induced Hypoalgesia (EIH) was assessed by evaluating the percentage of responses to a train of 60g mechanical stimuli before and after 180 seconds of exercise on a rotating rod. The differences in the response rates before and after the exercise were used to divide the rats into low and high EIH responders. Rats from low and high EIH groups underwent constriction injury of the left sciatic nerve. Pain behavior (allodynia and hyperalgesia) were assessed by measuring responses to mechanical and thermal stimuli applied to the plantar surface of the foot. Serum, sciatic nerve and the related Dorsal Root Ganglia (DRG) levels of IL-10 and IL-1beta were determined by ELISA. The DRG mRNA levels of IL-10 and IL-1beta measured with PCR. A comparison between the low and high EIH rats of all measured parameters was made. RESULTS: The low EIH rats developed significantly more severe allodynia and hyperalgesia in the affected paw and allodynia in the contralateral paw compared to the high EIH rats, 7 days following the injury. The low EIH rats had higher IL-1beta protein levels in serum prior to and following injury, higher affected and contralateral sciatic nerve IL-1beta levels following injury and higher IL-1beta levels in the contralateral DRG (protein and mRNA) following injury when compared to high EIH rats. The high EIH rats had higher affected sciatic nerve IL-10 levels following nerve injury and higher IL-10 levels of both protein and mRNA in the affected and contralateral DRG at baseline and following injury. CONCLUSION: EIH profile was found to be predictive of pain behavior following nerve injury, low EIH rats developed more severe allodynia and hyperalgesia. IL-1beta may be associated with painful neuropathy developed in rats with low EIH while the anti-inflammatory cytokine IL-10 may have a protective role, inhibiting the development of painful.

Molecular mechanisms of painful traumatic trigeminal neuropathy-Evidence from animal research and clinical correlates.

Painful traumatic trigeminal neuropathy (PTTN) may occur following major craniofacial or oral trauma, or may be subsequent to relatively minor dental interventions. Following injury, pain may originate from a peripheral nerve, a ganglion, or from the central nervous system. In this review, we focus on molecular mechanisms of pain resulting from injury to the peripheral branch of the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy (PTTN) by the International Headache Society and replaces previous terms including atypical odontalgia, deafferentation pain, traumatic neuropathy and phantom toothache. We emphasize the scientific evidence supporting the events purported to lead to PTTN by reviewing the pathophysiology of PTTN based on relevant animal models. Additionally, we briefly overview clinical correlates and pathophysiological manifestations of PTTN.

Altered pain modulation to noxious heat thermal stimuli in burning mouth syndrome.

OBJECTIVES: The aim of this study was to examine temporal summation (TS) and conditioned pain modulation (CPM) in patients with burning mouth syndrome (BMS) and healthy controls using intra-epidermal electrical stimulation (IES). MATERIALS AND METHODS: Twenty-six female patients with BMS and 27 healthy female controls participated in this study. A single stimulus with electrical stimulation followed by a train of 10 successive stimuli was administered to the right chin of participants in both the BMS and control groups. CPM was evaluated with the changes of TS calculated from the difference in numerical pain scale data between these two test stimuli and the following warm (40°C) and hot (47°C) conditioning stimuli applied at the non-dominant hand in both the BMS and control groups. RESULTS: TS was present in both the BMS and control groups. CPM in the BMS group was significantly less efficient at the 47°C condition than that in the control group, while no significant difference was observed in the CPM between the BMS and the control groups at the 40°C condition. CONCLUSION: These findings indicate that BMS is associated with a deficit inhibitory CPM and implicate the involvement of the central nervous system in the pathophysiology of BMS.

Interprofessional collaboration and smartphone use as promising strategies to improve prenatal oral health care utilization among US underserved women: results from a qualitative study.

BACKGROUND: Data on barriers and facilitators to prenatal oral health care among low-income US women are lacking. The objective of this study was to understand barriers/facilitators and patient-centered mitigation strategies related to the use of prenatal oral health care among underserved US women. METHODS: We used community-based participatory research to conduct two focus groups with eight pregnant/parenting women; ten individual in-depth interviews with medical providers, dental providers and community/social workers; and one community engagement studio with five representative community stakeholders in 2018-2019. Using an interpretive description research design, we conducted semi-structured interviews and focus groups which were audio-recorded, transcribed, and analyzed for thematic content. RESULTS: We identified individual and systemic barriers/facilitators to the utilization of prenatal oral health care by underserved US women. Strategies reported to improve utilization included healthcare system-wide changes to promote inter-professional collaborations, innovative educational programs to improve dissemination and implementation of prenatal oral health care guidelines, and specialized dental facilities providing prenatal oral health care to underserved women. Moreover, smartphones have the potential to be an innovative entry point to promote utilization of prenatal oral care at the individual level. CONCLUSIONS: Low-income women face multiple, addressable barriers to obtaining oral health care during pregnancy. Inter-professional collaboration holds strong promise for improving prenatal oral health care utilization.

Prenatal Oral Health Care and Early Childhood Caries Prevention: A Systematic Review and Meta-Analysis.

Despite the advancement of early childhood caries (ECC) prediction and treatment, ECC remains a significant public health burden in need of more effective preventive strategies. Pregnancy is an ideal period to promote ECC prevention given the profound influence of maternal oral health and behaviors on children's oral health. However, studies have shown debatable results with respect to the effectiveness of ECC prevention by means of prenatal intervention. Therefore, this study systematically reviewed the scientific evidence relating to the association between prenatal oral health care, ECC incidence, and Streptococcus mutans carriage in children. Five studies (3 randomized control trials, 1 prospective cohort study, and 1 nested case-control study) were included for qualitative assessment. Tested prenatal oral health care included providing fluoride supplements, oral examinations/cleanings, oral health education, dental treatment referrals, and xylitol gum chewing. Four studies that assessed ECC incidence reduction were included in meta-analysis using an unconditional generalized linear mixed effects model with random study effects and age as a covariate. The estimated odds ratio and 95% confidence intervals suggested a protective effect of prenatal oral health care against ECC onset before 4 years of age: 0.12 (0.02, 0.77) at 1 year of age, 0.18 (0.05, 0.63) at 2 years of age, 0.25 (0.09, 0.64) at 3 years of age, and 0.35 (0.12, 1.00) at 4 years of age. Children's S. mutans carriage was also significantly reduced in the intervention group. Future studies should consider testing strategies that restore an expectant mother's oral health to a disease-free state during pregnancy.

Association of somatosensory dysfunction with symptom duration in burning mouth syndrome.

OBJECTIVES: A standardized battery of quantitative sensory tests developed by the German Research Network on Neuropathic Pain (DFNS) was used to assess the association between somatosensory dysfunction and disease duration in patients with burning mouth syndrome (BMS). MATERIALS AND METHODS: The 28 female participants with BMS were classified according to disease duration: ≤ 6 months (subchronic BMS, n = 15) and > 6 months (chronic BMS, n = 13); 29 age- and sex-matched healthy volunteers (control group) were recruited from staff of a dental hospital. The DFNS quantitative sensory testing protocol was applied at the ulnar surface of the right forearm and the tip of the tongue. Values for BMS patients and controls were compared and analyzed. RESULTS: The mechanical detection threshold (MDT) was significantly higher (i.e., loss of sensation) at the tongue tip in the chronic BMS group than in the control group (p = 0.011), whereas mechanical pain sensitivity (MPS) at the forearm was significantly higher (i.e., gain of sensation) in the chronic BMS group than in the control group (Z score = - 2.13 and 1.99, respectively). Multivariate analyses revealed that BMS patients could be discriminated from controls by using pressure pain threshold at the tongue (79.3%) (in the subchronic BMS group) and by MDT and MPS at the tongue tip and MPS at the forearm (96.6 and 89.7%, respectively) (in the chronic BMS group). CONCLUSIONS: In BMS patients with long disease duration, MDT showed loss of sensation. CLINICAL RELEVANCE: Increased MPS suggests that a neuropathic mechanism in the peripheral and central nervous systems is involved in BMS development.

The effect of orthodontic separator and short-term fixed orthodontic appliance on inflammatory mediators and somatosensory function.

BACKGROUND: Although inflammation can alter cytokines release and nerve function, it is not yet fully established if orthodontic-induced inflammation can cause significant extraoral trigeminal somatosensory alterations and release of inflammatory chemical mediators. OBJECTIVE: The primary aim of this study was to investigate the impact of orthodontic separator and short-term fixed orthodontic appliance on the extraoral trigeminal somatosensory function and concentrations of cytokines in the gingival crevicular fluid (GCF). METHODS: Twenty-two female patients were evaluated as follow: baseline, 24 hour-after elastomeric separator (-aES), 24 hour- and 1 month-after bonding brackets (-aBB) at both arches. The outcome variables were as follows: self-reported pain (Visual Analog Scale), QSTs (current perception threshold-CPT, cold detection threshold-CDT, warm detection threshold-WDT, mechanical detection threshold-MDT, mechanical suprathreshold-MST and wind-up ratio-WUR. All QSTs were performed at infra-orbital and mental nerve entry zone at patient`s dominant side. In addition, GCF samples in order to assess cytokines profile (IL-1ß,IL-8,IL-6 and TNF-α) were collected. ANOVA and Tukey's post hoc analyses were performed (a = 5%). RESULTS: Patients reported higher pain intensity 24 hour-aBB compared to baseline and 24 hour-aES (P < 0.050). Patients were less sensitive to pin-prick pain (MST) at 24 hour-aBB and 1 month-aBB compared to baseline (P < 0.006). Significant increases in IL-6 levels were observed 24 hour-aBB (P < 0.001). Multiple comparison analysis showed significant increase in IL-1ß levels (P < 0.001) and TNF-α (P < 0.001) 1 month-aBB compared to baseline. CONCLUSION: Elastomeric separators only induced mild pain and were not able to significantly increase proinflammatory cytokines level in the GCF. In addition, orthodontic fixed appliance may induce only minor somatosensory changes at extraoral trigeminal locations.

Acute and chronic pain in orofacial trauma patients.

Trauma or injury to the dentition and supporting tissues is associated with pain and discomfort, as expected, that may present immediately, shortly afterwards, or within a few days. Pain is an essential response to injury because it allows the organism to develop avoidance behavior to potential threats and helps the organism to avoid usage of the injured organ during the healing process. Not only does external trauma induce pain, but also essential invasive dental procedures such as extractions, dental implant insertions, root canal treatments, and oral surgeries are accompanied by similar post-surgical (post-traumatic) pain. The pain intensity after trauma varies and does not always correlate with the extent of injury. Trauma to the orofacial region or the teeth may also indirectly affect and induce pain in other orofacial structures such as the masticatory muscles, the temporomandibular joint, and even the cervical spine. In most cases, the pain will resolve as soon as healing of the affected tissue occurs or after dental and routine palliative treatment. In a limited number of cases, the pain persists beyond healing and evolves into a chronic pain state. Chronic pain in the orofacial region presents diagnostic and management challenges. Misdiagnosis or delayed diagnosis of the oral chronic pain condition may lead to unnecessary dental treatment. This article will discuss diagnosis and treatment for acute and chronic pain as well as potential mechanisms involved in the undesirable transition from acute to chronic pain.

Effect of Pregabalin and Diclofenac on tactile allodynia, mechanical hyperalgesia and pro inflammatory cytokine levels (IL-6, IL-1ß) induced by chronic constriction injury of the infraorbital nerve in rats.

The present study evaluated the effects of systemic pregabalin (PG) and diclofenac (Dic) on neuropathic orofacial pain induced by chronic constriction injury (CCI) of the infraorbital nerve (ION) and on the pro-inflammatory cytokines levels in the affected nerve. Fifty-four rats underwent left infra orbital nerve CCI, and 7 days after the procedure as the pain developed, the rats were randomly assigned to one of the treatment groups: PG 300, 30 or 10 mg/kg, Dic 10, 5 or 1 mg/kg or saline group (Sal) (n/group = 8). Addiitonal 8 rats served as naïve control group. Tactile-allodynia and Mechano-hyperalgesia were tested before the surgical procedure and at days 7, 8, and 9 postoperatively. On the 9th day, the rats were euthanized and the affected and contralateral sciatic nerves were harvested to assess IL-6 and IL-1ß nerve levels employing enzyme linked immunosorbent assay (ELISA). Daily injection of PG (all doses) significantly reduced tactile-allodynia and mechano-hyperalgesia (p < .05) while Dic did not. On the 9th day, the ipsilateral nerve IL-6 levels were significantly decreased (p < .05) in the PG and DIC groups compared to the Sal group. IL-1ß levels demonstrated a significant reduction (p < .05) in the PG group when compared to saline. These results suggest that PG but not Dic may be effective in reducing neuropathic orofacial pain. The mechanisms of action may be associated to some extent with reduction in IL-1ß levels in the affected nerve.

Presentation of cysticercosis of the lateral pterygoid muscle as temporomandibular disorder: A diagnostic and therapeutic challenge.

Orofacial pain can often be the chief complaint of many systemic disorders. Cysticercosis involving the lateral pterygoids may cause limitation of mouth opening and may mimic clinical symptoms of a temporomandibular disorder. A 37-year-old female presented with 1-month-old complaint of limited mandibular range of motion. She reported a similar episode a year earlier and was diagnosed with a temporomandibular joint disorder by her primary dentist. Comprehensive intra- and extra-oral examinations were performed, which revealed a limitation of mouth opening accompanied by mild limitation of contralateral excursion. A magnetic resonance imaging revealed a ring-enhancing lesion within the left pterygoid muscle suggestive of cysticercosis. The patient was referred to her primary care physician for further treatment and given physical therapy (stretching exercises) to improve mouth opening. One week later, she developed lesions in the arm and trunk. Further ultrasound imaging of the abdomen and the forearms confirmed the diagnosis of cysticercosis. She was treated with albendazole, physiotherapy, joint stabilization appliance, and had eventual complete recovery. This case emphasizes the importance of diagnosis of a systemic condition that may have serious implications, if untreated, and the importance of a comprehensive evaluation, workup, and multidisciplinary management.

Role of Collagen Conduit With Duloxetine and/or Pregabalin in the Management of Partial Peripheral Nerve Injury.

PURPOSE: The objective of this study was to investigate the analgesic effect of a collagen conduit (Neuragen, Integra LifeSciences Corp, Plainsboro, NJ) using duloxetine (Cymbalta, Lilly, Indianapolis, IN) with or without pregabalin (Lyrica, Pfizer, NY) on pain induced by partial sciatic nerve transection in a rat model. MATERIAL AND METHODS: Adult male Sprague-Dawley rats were divided into 5 groups (n = 10 per group): group 1, nerve damage with no treatment; group 2, nerve damage treated with the application of a collagen conduit and saline; group 3, nerve damage treated with the application of a collagen conduit and duloxetine; group 4, nerve damage treated with the application of a collagen conduit and pregabalin; and group 5, nerve damage treated with the application of a collagen conduit and pregabalin plus duloxetine. Pain levels were evaluated by responses to mechanical and thermal stimuli at baseline before and 3 and 7 days after surgery. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) levels were evaluated in blood, sciatic nerve, and dorsal root ganglion samples collected 7 days after surgery. RESULTS: The group treated with the collagen conduit and pregabalin exhibited markedly less pain 7 days postoperatively in response to mechanical and thermal stimuli compared with the other groups. IL-10 levels were considerably increased in the group treated with pregabalin. The groups treated with a collagen conduit and duloxetine and a combination of pregabalin and duloxetine also exhibited markedly less pain in response to mechanical and thermal stimuli 7 days after surgery compared with the group that had only nerve injury. The decrease in pain using duloxetine was not as robust but was associated with a decrease of TNF-α. The combination of pregabalin and duloxetine resulted in a substantial decrease in IL-6. CONCLUSION: Using a collagen conduit and duloxetine, pregabalin, and their combination helped alleviate neuropathic pain. The mechanism of action might be associated, at least in part, to cytokines.

Temporomandibular joint osteoarthritis: diagnosis and long-term conservative management: a topic review.

Degenerative joint disease (DJD), a common osteoarthritic problem encountered in clinical practice presents as a chronic debilitating disease resulting in altered joint structure due to degradation and loss of articular cartilage, along with changes in the subchondral bone and other soft tissues. DJD is a frequent finding in the Temporomandibular joints (TMJs). Consequently, a good understanding of the use of a diagnostic algorithm will lead to a better control of DJD in the TMJ. The etiopathogenesis of osteoarthritis is complex, and it is associated with multiple risk factors. The condition progresses slowly through different phases with periods of remission and activity finally reaching the burnout phase. Conservative management forms the cornerstone for the treatment of most of these cases. This review attempts to acquaint the dentist with the diagnosis, pathogenesis and general characteristics of the disease while highlighting and updating them with the current conservative treatment algorithms in order to assist in the formulation of a treatment plan for these patients.

Time-Course Progression of Whole Transcriptome Expression Changes of Trigeminal Ganglia Compared to Dorsal Root Ganglia in Rats Exposed to Nerve Injury.

Mechanisms underlying neuropathic pain (NP) are complex with multiple genes, their interactions, environmental and epigenetic factors being implicated. Transcriptional changes in the trigeminal (TG) and dorsal root (DRG) ganglia have been implicated in the development and maintenance of NP. Despite efforts to unravel molecular mechanisms of NP, many remain unknown. Also, most of the studies focused on the spinal system. Although the spinal and trigeminal systems share some of the molecular mechanisms, differences exist. We used RNA-sequencing technology to identify differentially expressed genes (DEGs) in the TG and DRG at baseline and 3 time points following the infraorbital or sciatic nerve injuries, respectively. Pathway analysis and comparison analysis were performed to identify differentially expressed pathways. Additionally, upstream regulator effects were investigated in the two systems. DEG (differentially expressed genes) analyses identified 3,225 genes to be differentially expressed between TG and DRG in naïve animals, 1,828 genes 4 days post injury, 5,644 at day 8 and 9,777 DEGs at 21 days postinjury. A comparison of top enriched canonical pathways revealed that a number of signaling pathway was significantly inhibited in the TG and activated in the DRG at 21 days postinjury. Finally, CORT upstream regulator was predicted to be inhibited in the TG while expression levels of the CSF1 upstream regulator were significantly elevated in the DRG at 21 days postinjury. This study provides a basis for further in-depth studies investigating transcriptional changes, pathways, and upstream regulation in TG and DRG in rats exposed to peripheral nerve injuries. PERSPECTIVE: Although trigeminal and dorsal root ganglia are homologs of each other, they respond differently to nerve injury and therefore treatment. Activation/inhibition of number of biological pathways appear to be ganglion/system specific suggesting that different approaches might be required to successfully treat neuropathies induced by injuries in spinal and trigeminal systems.

Implementation of a 4Ms approach in age-friendly oral health care at an Academic Specialty Care Dental Clinic.

BACKGROUND: Implementing the Age-Friendly Health System (AFHS) framework into dental care provides a significant opportunity to link oral health to healthy aging. This project aimed to implement the AFHS 4Ms (what matters, medications, mentation, and mobility) in the provision of oral health care. This article describes the planning, integration, training development, and outcome measurements supporting a 4Ms approach at an academic dental clinic. METHODS: The Eastman Institute for Oral Health (EIOH) implemented screening instruments based on the 4Ms framework recommended for ambulatory care clinics by the Institute for Health Care Improvement (IHI). These ambulatory instruments were integrated into the workflows of a Specialty Care Clinic through the development of a plan-do-study-act cycle, utilization of available clinic resources, and creation of interdisciplinary collaborations. RESULTS: This project demonstrated the feasibility of implementing an AFHS checklist and tracking forms in dental practice by integrating available resources and prioritizing the 4Ms elements. This effort necessitated interdisciplinary collaborations between dental, medical, and social service professionals. It also created a new age-friendly focused education and training curriculum for dental residents and faculty. CONCLUSIONS: This pilot project is the first to establish dental standards for AFHS implementation, adapting the 4Ms assessment and metrics to oral health. This AFHS underscores key oral health processes, including assessment, planning, and personalized oral health care, adapted to the unique needs of the older adult population, especially those with cognitive impairment.

Anti-nociceptive effect of IL-12p40 in a rat model of neuropathic pain.

IL-12p70 is a proinflammatory cytokine secreted by dendritic cells, monocytes and macrophages. It plays a crucial role in cell-mediated immunity by inducing proliferation of T cell and natural killer cells, and enhancing their cytotoxic activity. In adaptive immune response, it acts on naive T cells to differentiate into Th1-type cells. It is composed of two subunits, p35 and p40. The latter can be secreted in the form of monodimer or heterodimer, which is also referred as IL-12p80. Recently IL-12p70 has been proven to locally provoke nociceptive effect in naïve rats. This study investigated pain response following systemic administration of IL-12p70 and IL-12p40 homodimer in chronic neuropathic pain model, induced by chronic constriction injury. The doses tested were IL-12p40 homodimer or IL12p70 at 15, 150 and 1500ng/kg, respectively. Pain was assessed at 1, 4, 7 and 24h after injection, in the form of tactile allodynia and mechanical hyperalgesia. The side effect of sensory motor disability was measured by rotarod performance. By all behavioral measures, IL-12p70 of any dosage, at any time point, had no significant effect on tactile allodynia and mechanical hyperalgesia. A high dose of IL-12p40 homodimer induced significant analgesic effect by the measure of hind paw tactile allodynia from 1h to 4h after injection. Medium and low doses of IL-12p40 homodimer exerted their analgesic effect 4h post injection. Mechanical hyperalgesia, following high and medium doses of IL-12p40 administration, was significantly reduced at 4h after application. Also, no significant sensory motor dysfunction was detected for all dosage for both homodimers. These findings suggest that systemic application of IL-12p40 homodimer induces time-dependent analgesia to mechanical stimulation in rats exposed to neuropathic pain.

Placenta-derived adherent cells attenuate hyperalgesia and neuroinflammatory response associated with perineural inflammation in rats.

Neuropathic pain is a debilitating condition of the somatosensory system caused by pathology of the nervous system. Current drugs treat symptoms but largely fail to target the underlying mechanisms responsible for the pathological changes seen in the central or peripheral nervous system. We investigated the therapeutic effects of PDA-001, a culture expanded placenta-derived adherent cell, in the rat neuritis model. Pain is induced in the model by applying carrageenan to the sciatic nerve trunk, causing perineural inflammation of the sciatic nerve. PDA-001, at doses ranging from 0.4×10(6) to 4×10(6) cells/animal, or vehicle control was intravenously administrated to assess the biological activity of the cells. A dose-dependent effect of PDA-001 on pain relief was demonstrated. PDA-001 at doses of 1×10(6) and 4×10(6), but not 0.4×10(6), reduced mechanical hyperalgesia within 24h following treatment and through day 8 after induction of neuritis. The mechanism underlying PDA-001-mediated reduction of neuroinflammatory pain was also explored. Ex vivo tissue analyses demonstrated that PDA-001 suppressed homing, maturation and differentiation of dendritic cells, thus inhibiting T-cell priming and activation in draining lymph nodes. PDA-001 also reduced interferon gamma and IL-17 in draining lymph nodes and in the ispilateral sciatic nerve, and increased the levels of IL-10 in draining lymph nodes and plasma, pointing to T-cell modulation as a possible mechanism mediating the observed anti-hyperalgesic effects. Furthermore, in the ipsilateral sciatic nerve, significantly less leukocyte infiltration was observed in PDA-001-treated animals. The results suggest that PDA-001may provide a novel therapeutic approach in the management of inflammatory neuropathic pain and similar conditions.

Is there a role for a collagen conduit and anti-inflammatory agent in the management of partial peripheral nerve injuries?

PURPOSE: The purpose of this study was to investigate the effect of a collagen conduit and an anti-inflammatory agent in the treatment of acute partial sciatic nerve injuries in a rat chronic constrictive injury (CCI) model. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into 5 groups: group 1 (nerve damage with no treatment), group 2 (nerve damage and collagen tube), group 3 (nerve damage and collagen tube treated with anti-inflammatory agent), group 4 (sham surgery), and group 5 (naive rat). Each group consisted of 10 study animals. The nerve injury model used was the CCI model. Behavioral responses to thermal and mechanical stimuli were tested at 3, 7, and 14 days after surgery. Transverse sections of nerve tissue were harvested at day 14 and evaluated by standard error of mean (SEM). RESULTS: Tactile allodynia measurements showed initial increases in the threshold at day 3, followed by a significant decrease at day 7, and consistently remained lower than baseline by day 14. Heat allodynia measurements at day 3 showed a statistically significant decrease in threshold compared with the CCI group. However, at days 7 and 14, the threshold was not statistically different from the CCI group threshold. Groups with and without anti-inflammatory agents at day 7 showed a statistically significant decrease in threshold to both heat and tactile allodynia from day 3, indicating that groups with collagen and anti-inflammatory treatment had significant decreases in both heat and tactile allodynia. A similar relationship was observed at day 14. Transverse sections of nerve tissue evaluated by SEM of nerve tissue revealed a broad distribution of axons in group 1, with the greatest interaxonal distance in cross sections. Group 2 displayed less interaxonal distance compared with group 1, and group 3 had the least interaxonal distance. CONCLUSIONS: This study demonstrated a statistically significant decrease in pain secondary to the application of a collagen conduit and anti-inflammatory agent. Behavioral testing and SEM data also support the finding of a decrease in edema in the presence of a collagen conduit, with the greatest decrease being in the presence of both collagen conduit and anti-inflammatory agent.

Editorial: Chronic Orofacial Pain in Older Adults.

No summary.

Systemic Factors in Temporomandibular Disorder Pain.

The science of temporomandibular disorder (TMD) pain and its management has gone through significant changes during the last several decades. The authors strongly feel that the effect of systemic factors influencing TMD pain has been largely overlooked and poorly accounted for, even in established pain-management programs and protocols. The hope is that this article will act as a wake-up call for the pain management community to consider the importance of adequate knowledge of the systemic factors that affect the experience of TMD pain by the patient.