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In the course of investigating how common clinical treatments and adaptive technologies affect recovery after spinal cord injury (SCI), we discovered that a clinically-modeled hindlimb stretching protocol dramatically, but transiently, reduces locomotor function. Nociceptive sensory input is capable of altering motor output at the spinal level, and nociceptive neurons are sensitized after SCI. Here we tested the possibility that the stretch-induced motor deficits required the presence of nociceptors using neonatal capsaicin induced depletion of TRPV1+ nociceptive neurons. Following maturation, animals received 25 g-cm contusive SCI at T10. After plateau of locomotor recovery at 6 weeks, daily stretching was performed for 3 weeks, followed by 2 weeks without stretch, and again for two additional weeks. Animals were sacrificed 2 h after the last stretching session for histological assessments. The expected stretch-induced drops in locomotor function were observed in nociceptor-intact animals but were nearly absent in nociceptor-depleted animals. These functional changes were accompanied by corresponding increases in the number of c-Fos + nuclei throughout the lumbar enlargement. As expected, nociceptor-depleted animals had very little CGRP+ axonal innervation of the dorsal horn. However, in nociceptor-intact animals the expected post-SCI increase in CGRP+ innervation was significantly enhanced in animals that received stretching, implying additional stretch-induced intraspinal sprouting. These results indicate that locomotor dysfunction following hindlimb muscle stretch in animals with incomplete SCI involves C-fibers, adding a negative post-SCI role to their adaptive roles (e.g., bladder control), and suggesting that the clinical use of muscle stretching to combat contractures and spasticity may be unintentionally detrimental to locomotor function.
Learn More >Endometriosis, a systemic disease that is often painful and chronic, affects ∼10% of reproductive-age women. The disease can negatively impact a patient's physical and emotional well-being, quality of life, and productivity. Endometriosis also places significant economic and social burden on patients, their families, and society as a whole. Despite its high prevalence and cost, endometriosis remains underfunded and under-researched – greatly limiting our understanding of the disease and slowing much-needed innovation in diagnostic and treatment options. Due in part to the societal normalization of women's pain and stigma around menstrual issues, there is also a lack of disease awareness among patients, health care providers, and the public. The Society for Women's Health Research convened an interdisciplinary group of expert researchers, clinicians, and patients for a roundtable meeting to review the current state of the science on endometriosis and identify areas of need to improve a woman's diagnosis, treatment, and access to quality care. Comprehensive and interdisciplinary approaches to disease management and increased education and disease awareness for patients, health care providers, and the public are needed to remove stigma, increase timely and accurate diagnosis and treatment, and allow for new advancements.
Learn More >Small nerve fibers that bind the isolectin B4 (IB4 C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidate the functional role of IB4-nociceptors in different models of pain. However, a functional characterization of the non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice is still lacking. To this end, in the present study, the neurotoxin IB4-Saporin (IB4-Sap) was employed to ablate non-peptidergic C-fibers. Firstly, we showed that intrathecal (i.t.) administration of IB4-Sap in mice depleted non-peptidergic C-fibers, since it decreased the expression of purinoceptor 3 (P2X) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the dorsal root ganglia (DRGs) as well as IB4 labelling in the spinal cord. Non-peptidergic C-fibers depletion did not alter the mechanical nociceptive threshold, but it inhibited the mechanical inflammatory hypersensitivity induced by glial cell-derived neurotrophic factor (GDNF), but not nerve growth factor (NGF). Depletion of non-peptidergic C-fibers abrogated mechanical inflammatory hypersensitivity induced by carrageenan. Finally, it was found that the inflammatory mediators PGE and epinephrine produced a mechanical inflammatory hypersensitivity that was also blocked by depletion of non-peptidergic C-fibers. These data suggest that IB4-positive nociceptive nerve fibers are not involved in normal mechanical nociception but are sensitised by inflammatory stimuli and play a crucial role in mediating mechanical inflammatory hypersensitivity.
Learn More >The associations between family strain, depression, and chronic pain interference vary across individuals, suggesting moderated relations, and one possible moderator is somatic amplification. The current study examined a moderated mediation model that investigated (a) whether depression mediated the relation between non-spouse family strain and chronic pain interference and (b) whether somatic amplification moderated the association between depression and chronic pain interference.
Learn More >Transient receptor potential ankyrin 1 (TRPA1) channels may have a role in migraine as some substances known to cause headache activate the channel. In the craniovascular system such activation causes a calcitonin gene-related peptide (CGRP)-dependent increase in meningeal blood flow. TRPA1 channels in the endothelium of cerebral arteries cause vasodilation when activated. The headache preventive substance feverfew inhibits activation of TRPA1 channels. In this study we aim to compare and characterize the effect of the TRPA1 agonist allyl isothiocyanate (AITC) on the diameter of rat dural and pial arteries in vivo.
Learn More >Spinal cord injury (SCI) is a tragic event causing irreversible losses of sensory, motor, and autonomic functions, that may also be associated with chronic neuropathic pain. Serotonin (5-HT) neurotransmission in the spinal cord is critical for modulating sensory, motor, and autonomic functions. Following SCI, 5-HT axons caudal to the lesion site degenerate, and the degree of axonal degeneration positively correlates with lesion severity. Rostral to the lesion, 5-HT axons sprout, irrespective of the severity of the injury. Unlike callosal fibers and cholinergic projections, 5-HT axons are more resistant to an inhibitory milieu and undergo active sprouting and regeneration after central nervous system (CNS) traumatism. Numerous studies suggest that a chronic increase in serotonergic neurotransmission promotes 5-HT axon sprouting in the intact CNS. Moreover, recent studies in invertebrates suggest that 5-HT has a pro-regenerative role in injured axons. Here we present a brief description of 5-HT discovery, 5-HT innervation of the CNS, and physiological functions of 5-HT in the spinal cord, including its role in controlling bladder function. We then present a comprehensive overview of changes in serotonergic axons after CNS damage, and discuss their plasticity upon altered 5-HT neurotransmitter levels. Subsequently, we provide an in-depth review of therapeutic approaches targeting 5-HT neurotransmission, as well as other pre-clinical strategies to promote an increase in re-growth of 5-HT axons, and their functional consequences in SCI animal models. Finally, we highlight recent findings signifying the direct role of 5-HT in axon regeneration and suggest strategies to further promote robust long-distance re-growth of 5-HT axons across the lesion site and eventually achieve functional recovery following SCI.
Learn More >Diet restriction and exercise form key treatments for osteoarthritis (OA) related symptoms in overweight and obese individuals. Although both interventions are known to influence systemic low-grade inflammation, which is related to pain levels and functional limitations, little is known about the potential changes in systemic inflammation as a working mechanism of diet restriction and exercise in knee OA.
Learn More >Occupational medicine seeks to reduce sick leave; however, evidence for an add-on effect to usual care is sparse. The objective of the GOBACK trial was to test whether people with low back pain (LBP) in physically demanding jobs and at risk of sick leave gain additional benefit from a 3-month complex intervention that involves occupational medicine consultations, a work-related evaluation and workplace intervention plan, an optional workplace visit, and a physical activity program, over a single hospital consultation and an MRI.
Learn More >Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P < 0.05), a lower CPM response (P = 0.02), more functional disability (P < 0.001), and pain-related fear (P < 0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P < 0.001). No sex differences were found for the experimental pain measurements (P > 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.
Learn More >Opioid overuse remains rampant even in hospitals, but whether administrative opioid safety initiatives reduce use remains unclear WHAT THIS ARTICLE TELLS US THAT IS NEW: The authors evaluated the effects of a Veterans Administration national Opioid Safety Initiative using interrupted time series analysis to compare trends before and after starting the initiativeThere was a trivial increase in pain scores, and a substantial reduction in patients with chronic preoperative and postoperative opioid prescriptions BACKGROUND:: The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty.
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