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The characteristics of self-reported functional limitations among older United States (US) adults with pain are currently unknown. This cross-sectional study aimed to determine the characteristics associated with functional limitations among non-institutionalized older (≥50 years) US adults with pain using 2017 Medical Expenditure Panel Survey (MEPS) data. Eligible subjects were alive for the calendar year, aged ≥50 years, and experienced pain within the past four weeks. Hierarchical logistic regression models were utilized to determine significant characteristics associated with functional limitations (outcome variable; yes, no). Functional limitations included difficulty with bending, stooping, climbing stairs, grasping objects, lifting, reaching overhead, standing for long periods of time, or walking. Extrapolation of national data values was possible by adjusting for the complex MEPS design. We found approximately 22 million of the 57 million older US adults (≥50 years) who reported pain had a functional limitation in 2017. Characteristics associated with functional limitations included: gender, race, ethnicity, employment status, marital status, pain intensity, physical health, number of chronic conditions, and frequent exercise status. Knowledge of characteristics associated with functional limitations may provide an opportunity to identify and resolve gaps in patient care among this population.
Learn More >The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.
Learn More >Chronic back and neck pain are highly prevalent conditions that are among the largest drivers of physical disability and cost in the world. Recent clinical practice guidelines recommend use of non-pharmacologic treatments to decrease pain and improve physical function for individuals with back and neck pain. However, delivery of these treatments remains a challenge because common care delivery models for back and neck pain incentivize treatments that are not in the best interests of patients, the overall health system, or society. This narrative review focuses on the need to increase use of non-pharmacologic treatment as part of routine care for back and neck pain. First, we present the evidence base and summarize recommendations from clinical practice guidelines regarding non-pharmacologic treatments. Second, we characterize current use patterns for non-pharmacologic treatments and identify potential barriers to their delivery. Addressing these barriers will require coordinated efforts from multiple stakeholders to prioritize evidence-based non-pharmacologic treatment approaches over low value care for back and neck pain. These stakeholders include patients, health care providers, health care organizations, administrators, payers, policymakers and researchers.
Learn More >To determine how many persons with knee pain have subsequent pain resolution and what factors are associated with resolution, focusing especially on types of physical activity.
Learn More >To examine the prevalence of comorbid conditions in a nationwide population of men and women with IC/BPS utilizing a more heterogeneous sample than most studies to date.
Learn More >Highly conserved amino acids are generally anticipated to have similar functions across a protein superfamily, including that of the P2X ion channels, which are gated by extracellular ATP. However, whether and how these functions are conserved becomes less clear when neighboring amino acids are not conserved. Here, we investigate one such case, focused on the highly conserved residue from P2X4, E118 (rat P2X4 numbering, rP2X4), a P2X subtype associated with human neuropathic pain. When we compared the crystal structures of P2X4 with those of other P2X subtypes, including P2X3, P2X7 and AmP2X, we observed a slightly altered side-chain orientation of E118. We used protein chimeras, double mutant cycle analysis and molecular modeling to reveal that E118 forms specific contacts with amino acids in the "beak" region, which facilitates ATP binding to rP2X4. These contacts are not present in other subtypes due to sequence variance in the beak region, resulting in decoupling of this conserved residue from ATP recognition and/or channel gating of P2X receptors. Our study provides an example of a conserved residue with a specific role in functional proteins enabled by adjacent non-conserved residues. The unique role established by the E118-beak region contact provides a blueprint for the development of subtype-specific inhibitors of P2X4.
Learn More >Determine the association of chronic conditions measured at baseline with physical performance and falls over time among older adults with back pain. We examined both number and type (depression, anxiety, and arthritis) of chronic conditions.
Learn More >Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown.
Learn More >In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22, and histamine, which activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.
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