Kringmccullough5899

Chronic pain is a growing public health crisis that requires exigent and efficacious therapeutics. GPR171 is a promising therapeutic target that is widely expressed through the brain, including within the descending pain modulatory regions. Here, we explore the therapeutic potential of the GPR171 agonist, MS15203, in its ability to alleviate chronic pain in male and female mice using a once-daily systemic dose (10 mg/kg, i.p.) of MS15203 over the course of 5 days. We found that in our models of Complete Freund's Adjuvant (CFA)-induced inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN), MS15203 did not alleviate thermal hypersensitivity and allodynia, respectively, in female mice. On the other hand, MS15203 treatment decreased the duration of thermal hypersensitivity in CFA-treated male mice following 3 days of once-daily administration. MS15203 treatment also produced an improvement in allodynia in male mice, but not female mice, in neuropathic pain after 5 days of treatment. Gene expression of GPR171 and that of its endogenous ligand BigLEN, encoded by the gene PCSK1N, were unaltered within the periaqueductal gray (PAG) in both male and female mice following inflammatory and neuropathic pain. However, following neuropathic pain in male mice, the protein levels of GPR171 were decreased in the PAG. Treatment with MS15203 then rescued the protein levels of GPR171 in the PAG of these mice. Taken together, our results identify GPR171 as a GPCR that displays sexual dimorphism in alleviation of chronic pain. Further, our results suggest that GPR171 and MS15203 have demonstrable therapeutic potential in the treatment of chronic pain.Temporomandibular joint disorders (TMD) consist of a heterogeneous group of conditions that present with pain in the temporomandibular joint (TMJ) region and muscles of mastication. This project assessed the role of connexin 43 (Cx43), a gap junction protein, in the trigeminal ganglion (TG) in an animal model for persistent inflammatory TMJ hyperalgesia. Experiments were performed in male and female rats to determine if sex differences influence the expression and/or function of Cx43 in persistent TMJ hyperalgesia. Intra-TMJ injection of Complete Freund's Adjuvant (CFA) caused a significant increase in Cx43 expression in the TG at 4 days and 10 days post-injection in ovariectomized (OvX) female rats and OvX females treated with estradiol (OvXE), while TG samples in males revealed only marginal increases. Intra-TG injection of interference RNA for Cx43 (siRNA Cx43) 3 days prior to recording, markedly reduced TMJ-evoked masseter muscle electromyographic (MMemg) activity in all CFA-inflamed rats, while activity in sham animals was not affected. Western blot analysis revealed that at 3 days after intra-TG injection of siRNA Cx43 protein levels for Cx43 were significantly reduced in TG samples of all CFA-inflamed rats. Intra-TG injection of the mimetic peptide GAP19, which inhibits Cx43 hemichannel formation, greatly reduced TMJ-evoked MMemg activity in all CFA-inflamed groups, while activity in sham groups was not affected. These results revealed that TMJ inflammation caused a persistent increase in Cx43 protein in the TG in a sex-dependent manner. However, intra-TG blockade of Cx43 by siRNA or by GAP19 significantly reduced TMJ-evoked MMemg activity in both males and females following TMJ inflammation. These results indicated that Cx43 was necessary for enhanced jaw muscle activity after TMJ inflammation in males and females, a result that could not be predicted on the basis of TG expression of Cx43 alone.Objectives (1) Validate thresholds for minimal, low, moderate, and high fear of movement on the 11-item Tampa Scale of Kinesiophobia (TSK-11), and (2) Establish a patient-driven minimal clinically important difference (MCID) for Achilles tendinopathy (AT) symptoms of pain with heel raises and tendon stiffness. Methods Four hundred and forty-two adults with chronic AT responded to an online survey, including psychosocial questionnaires and symptom-related questions (severity and willingness to complete heel raises and hops). Kinesiophobia subgroups (Minimal ≤ 22, Low 23-28, Moderate 29-35, High ≥ 36 scores on the TSK-11), pain MCID subgroups (10-, 20-, 30-, >30-points on a 0- to 100-point scale), and stiffness MCID subgroups (5, 10, 20, >20 min) were described as median [interquartile range] and compared using non-parametric statistics. Results Subgroups with higher kinesiophobia reported were less likely to complete three heel raises (Minimal = 93%, Low = 74%, Moderate = 58%, High = 24%). Higher kinesiophobia was associated with higher expected pain (Minimal = 20.0 [9.3-40.0], Low = 43.0 [20.0-60.0], Moderate = 50.0 [24.0-64.0], High = 60.5 [41.3-71.0]) yet not with movement-evoked pain (Minimal = 25.0 [5.0-43.0], Low = 31.0 [18.0-59.0], Moderate = 35.0 [20.0-60.0], High = 43.0 [24.0-65.3]). The most common pain MCID was 10 points (39% of respondents). Half of respondents considered a 5-min (35% of sample) or 10-min (16%) decrease in morning stiffness as clinically meaningful. Conclusions Convergent validity of TSK-11 thresholds was supported by association with pain catastrophizing, severity of expected pain with movement, and willingness to complete tendon loading exercises. Most participants indicated that reducing their pain severity to the mild range would be clinically meaningful.Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a "new" TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized ordewo protocols may tap into entirely different mechanisms, especially in the case of TSP.Background and Aims Irritable bowel syndrome (IBS), a functional pain disorder of gut-brain interactions, is characterized by a high placebo response in randomized clinical trials (RCTs). Catechol-O-methyltransferase (COMT) rs4680, which encodes high-activity (val) or low-activity (met) enzyme variants, was previously associated with placebo response to sham-acupuncture in an IBS RCT. Examining COMT effects and identifying novel genomic factors that influence response to placebo pills is critical to identifying underlying mechanisms and predicting and managing placebos in RCTs. Methods Participants with IBS (N = 188) were randomized to three placebo-related interventions, namely, double-blind placebo (DBP), open-label placebo (OLP), or simply trial enrollment without placebo treatment [no placebo (i.e., no pill) treatment control (NPC)], for 6 weeks. COMT rs4680, gene-set, and genome-wide suggestive (p less then 10-5) loci effects on irritable bowel symptom severity score (IBS-SSS) across all participants wration ClinicalTrials.gov, Identifier NCT0280224.Over 50% of the 34 million people who suffer from diabetes mellitus (DM) are affected by diabetic neuropathy. Painful diabetic neuropathy (PDN) impacts 40-50% of that group (8.5 million patients) and is associated with a significant source of disability and economic burden. Though new neuromodulation options have been successful in recent clinical trials (NCT03228420), still there are many barriers that restrict patients from access to these therapies. We seek to examine our tertiary care center (Albany Medical Center, NY, USA) experience with PDN management by leveraging our clinical database to assess patient referral patterns and utilization of neuromodulation. We identified all patients with a diagnosis of diabetes type 1 (CODE E10.xx) or diabetes type 2 (CODE E11.xx) AND neuralgia/neuropathic pain (CODE M79.2) or neuropathy (CODE G90.09) or chronic pain (CODE G89.4) or limb pain (CODE M79.6) OR diabetic neuropathy (CODE E11.4) who saw endocrinology, neurology, and/or neurosurgery from January 1, 2019, toodulation. The patients on three or more pain medications without symptomatic relief may be potential candidates for neuromodulation. An opportunity, therefore, exists to educate providers on the benefits of neuromodulation procedures.Background Assessment of pain largely relies on self-report. Hospitals routinely use pain scales, such as the Verbal Rating Scale (VRS), to record patients' pain, but such scales are unidimensional, concatenating pain intensity and other dimensions of pain with significant loss of clinical information. click here This study explored how inpatients understand and use the VRS in a hospital setting. Methods Forty five participants were interviewed, with data analysed by thematic analysis, and completed a task concerned with the VRS and communication of other dimensions of pain. Results Participants anchored their pain experience in the physical properties of pain, its tolerability, and its impact on functioning. Their relationship to analgesic medication, personal coping styles, and experiences of staff all influenced how they used the VRS to communicate their pain. Conclusion Participants grounded and explained their pain in semantically similar but idiosyncratic ways. The VRS was used to combine pain intensity with multiple other elements of pain and often as a way to request analgesic medication. Pain scores need to be explored and elaborated by patient and staff, content of which will imply access to non-pharmacological resources to manage pain.Cancer pain has been shown to have a significant negative impact on health-related quality of life (HRQoL) for people experiencing it. This is also true for patients admitted to inpatient rehabilitation facilities (IRFs). An interdisciplinary approach is often needed to fully address a person's pain to help them attain maximum functional independence and to ensure a safe discharge home. Improving a patient's performance status in an IRF may also be a crucial determinant in their ability to continue receiving treatment for their cancer. However, if a person is determined to no longer be a candidate for aggressive, disease modulating treatment, IRFs can also be utilized to help patients and family's transition to comfort directed care with palliative or hospice services. This article will discuss the interventions of the multidisciplinary inpatient rehabilitation team to address a person's pain.Aims This study explores the association between subjective feeling of stress and pain experience in the context of the COVID-19 pandemic with a focus on characteristics known to trigger a physiological stress response [sense of low control, threat to ego, unpredictability and novelty (STUN)]. Methods This exploratory longitudinal convergent mixed methods design consisted of online questionnaires over three time points (before, during and after the 1st wave of the COVID-19 pandemic) (N = 49) and qualitative interviews (N = 27) during the 1st wave of the pandemic on distinct samples of individuals living with chronic pain (CP). Both types of data sources were mixed upon integration using joint display. Results Mean pain intensity scores remained stable across time points, while pain unpleasantness and pain interference scores significantly improved. Global impression of change scores measured during the first wave of the pandemic do not entirely concord with pain scores evolution. Two thirds of participants reported a global deterioration of their pain condition at the beginning of the pandemic.