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Patients suffering with functional somatic pain syndromes such as temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) have some similar symptoms, but the underlying cause is still unclear. The purpose of this study was to investigate whether 5-HT and 5-HT receptors in the spinal cord contribute to somatic hyperalgesia induced by orofacial inflammation combined with different modes of stress. Ovariectomized rats were injected subcutaneously with estradiol and bilateral masseter muscles were injected with complete Freund's adjuvant followed by stress. Somatic sensitivity was assessed with thermal and mechanical stimulation. The anxiety- and depression-like behaviors were measured by immobility time, sucrose preference, elevated plus maze and open field tests. The expression of 5-HT and 5-HT receptors in the spinal cord was examined by western blot. Orofacial inflammation combined with 11 day forced swim stress (FSS) induced persistent mechanical allodynia for 15 days and thermal hyperalgesia for 2 days. The mechanical and thermal hyperalgesia lasted for 43 days and 30 days respectively following orofacial inflammation combined with 11 day heterotypic stress. Orofacial inflammation combined with stress induced anxiety- and depression-like behaviors. The expression of 5-HT and 5-HT receptors significantly decreased in the orofacial inflammation combined with stress groups. Intrathecal injection of 5-HT or 5-HT receptor agonist reversed somatic hyperalgesia. The results suggest that down-regulation of 5-HT and 5-HT receptors in the spinal cord contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, indicating that 5-HT and 5-HT receptors may be potential targets in the treatment of TMD comorbid with FMS.
Learn More >Genetic polymorphisms have been shown to affect opioid requirement for pain relief. However, true genetic effect is often difficult to assess due to underlying pain conditions and placebo effects. The goal of this study was to understand how common polymorphisms affect opioid effects while controlling for these factors. A randomized, double-blind, placebo-controlled study was implemented to assess how opioid effects are modulated by COMT (rs6269, rs4633, rs4848, rs4680), OPRM1 (A118G), and OPRK1 (rs1051660, rs702764, rs16918875). One hundred and eight healthy subjects underwent experimental pain testing before and after morphine, butorphanol, and placebo (saline). Association analysis was performed between polymorphisms/haplotypes and opioid response, while correcting for race, gender, placebo effects, and multiple comparisons. Pressure pain was significantly associated with rs6269 and rs4633 following butorphanol. The AA genotype of rs4680 or A_T_C_A/ A_T_C_A (rs6269_rs4633_ rs4818_rs4680) diplotype of COMT, combined with the AG genotype of OPRM1 A118G, showed significantly increased pressure pain threshold from butorphanol. Opioid effects on pressure, ischemic, heat pain, and side effects were nominally associated with several SNPs and haplotypes. Effects were often present in one opioid but not the other. This indicates that these polymorphisms affect pain relief from opioids, and that their effects are opioid and pain modality specific.
Learn More >Multimodal analgesic approaches are recommended for ICU pain management. Although music is known to reduce pain in acute and chronic care settings, less is known about its effectiveness in the adult ICU.
Learn More >Chronic pruritus, or itch lasting >6 weeks, is a common symptom and has a profoundly negative impact on quality of life. While many primary dermatologic disorders such as atopic dermatitis and chronic urticaria are characterized by pruritus, numerous other allergic, hepatobiliary, lymphoproliferative, neurologic, and renal disorders are associated with chronic pruritus. Itch involves complex interactions orchestrated by a variety of factors released from and acting on the skin, immune system, and the sensory nervous system. This review summarizes recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways.
Learn More >The role of gender, race, and socioeconomic status in outcomes and satisfaction are reflected in patient-reported outcomes using measurement tools representing outcome domains. These domains include pain relief, physical and emotional functioning, adverse events, participant disposition, and patient satisfaction. Measurement tools exist for each of the outcomes in both acute and chronic pain. Patients with lower economic status have greater difficulty accessing care, are involved less in shared decision-making process, and are less satisfied with their care. Blacks, Hispanics, and Asians also have increased difficulty in accessing good quality care. Women have inferior outcomes after medical and surgical interventions.
Learn More >Opioid Dose and Benzodiazepine Use Among Commercially Insured Individuals on Chronic Opioid Therapy.
To examine morphine milligram equivalent (MME) trends, use of concurrent opioids and benzodiazepines, and opioid-related emergency department (ED) visits or hospitalizations in a national cohort of patients on chronic opioid therapy.
Learn More >While alterations in spinal kinematics have been repeatedly observed in chronic low back pain (CLBP) patients, their exact nature is still unknown. Specifically, there is a need for comprehensive assessments of multi-segment spinal angles during daily-life activities. The purpose of this exploratory study was to characterize three-dimensional angles at the lower lumbar, upper lumbar, lower thoracic and upper thoracic joints in CLBP patients and asymptomatic controls during stepping up with three different step heights. Spinal angles of 10 patients with non-specific CLBP (6 males; 38.7±7.2 years old; 22.3±1.6 kg/m ) and 11 asymptomatic individuals (6 males; 36.7±5.4 years old; 22.9±3.8 kg/m ) were measured in a laboratory using a camera-based motion capture system. Seven out of the 12 angle curves had characteristic patterns, leading to the identification of 20 characteristic peaks. Comparing peak amplitudes between groups revealed statistically significantly smaller sagittal- and frontal-plane angles in the patient group at the upper lumbar joint with the two higher steps and at the lower lumbar joint with the higher step. Significantly reduced angles were also observed in sagittal-plane at the upper thoracic joint with the two smaller steps. Moreover, a higher number of significant differences between groups was detected with the two higher steps than with the smallest step. In conclusion, this study showed the value of a comprehensive description of spinal angles during step-up tasks and provided insights into the alterations with CLBP. These preliminary results support prior research suggesting that CLBP rehabilitation should facilitate larger amplitudes of motion during functional activities. This article is protected by copyright. All rights reserved.
Learn More >The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing. Onset of pneumonia and ARDS can be rapid in COVID-19, suggesting a potential neuronal involvement in pathology and mortality. We hypothesized that SARS-CoV-2 infection drives changes in immune cell-derived factors that then interact with receptors expressed by the sensory neuronal innervation of the lung to further promote important aspects of disease severity, including ARDS. We sought to quantify how immune cells might interact with sensory innervation of the lung in COVID-19 using published data from patients, existing RNA sequencing datasets from human dorsal root ganglion neurons and other sources, and a genome-wide ligand-receptor pair database curated for pharmacological interactions relevant for neuro-immune interactions. Our findings reveal a landscape of ligand-receptor interactions in the lung caused by SARS-CoV-2 viral infection and point to potential interventions to reduce the burden of neurogenic inflammation in COVID-19 pulmonary disease. In particular, our work highlights opportunities for clinical trials with existing or under development rheumatoid arthritis and other (e.g. CCL2, CCR5 or EGFR inhibitors) drugs to treat high risk or severe COVID-19 cases.
Learn More >The dorsolateral prefrontal cortex (dlPFC) is functionally linked to the descending pain modulation system and has been implicated in top down pain inhibition, including placebo analgesia. Therefore, functions of the dlPFC may be impaired in patients with chronic pain. Postherpetic neuralgia (PHN) is one of several syndromes with chronic neuropathic pain. In the present study, we investigated possible dysfunction of the dlPFC in chronic pain using patients with PHN. In a conditioning phase, heathy controls (n = 15) and patients with PHN (n = 7) were exposed to low (LF) and high (HF) frequency tones associated with noxious stimuli: weak (WS) and strong (SS) electrical stimulation, respectively. After the conditioning, cerebral hemodynamic activity was recorded from the bilateral dlPFC while the subjects were subjected to the cue tone-noxious electrical stimulation paradigm, in which incorrectly cued noxious stimuli were sometimes delivered to induce placebo and nocebo effects. The results indicated that hemodynamic responses to the LF tone in the right dlPFC was significantly lower in patients with PHN compared to the healthy controls. Furthermore, the same hemodynamic responses in the right dlPFC were correlated with placebo effects. In addition, clinical symptoms of PHN were negatively correlated to cerebral hemodynamic responses in the right dlPFC and magnitudes of the placebo effects. The results suggest that the right dlPFC, which is closely associated with the descending pain modulation system, is disturbed in PHN.
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