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The continued prevalence of chronic low back pain (CLBP) is a testament to our lack of understanding of the potential causes, leading to significant treatment challenges. CLBP is the leading cause of years lived with disability and the fifth leading cause of disability-adjusted life-years. No single non-pharmacologic, pharmacologic, or interventional therapy has proven effective as treatment for the majority of patients with CLBP. Although non-pharmacologic therapies are generally helpful, they are often ineffective as monotherapy and many patients lack adequate access to these treatments. Noninvasive treatment measures supported by evidence include physical and chiropractic therapy, yoga, acupuncture, and non-opioid and opioid pharmacologic therapy; data suggest a moderate benefit, at most, for any of these therapies. Until our understanding of the pathophysiology and treatment of CLBP advances, clinicians must continue to utilize rational multimodal treatment protocols. Recent Centers for Disease Control and Prevention guidelines for opioid prescribing recommend that opioids not be utilized as first-line therapy and to limit the doses when possible for fear of bothersome or dangerous adverse effects. In combination with the current opioid crisis, this has caused providers to minimize or eliminate opioid therapy when treating patients with chronic pain, leaving many patients suffering despite optimal nonopioid therapies. Therefore, there remains an unmet need for effective and tolerable opioid receptor agonists for the treatment of CLBP with improved safety properties over legacy opioids. There are several such agents in development, including opioids and other agents with novel mechanisms of action. This review critiques non-pharmacologic and pharmacologic treatment modalities for CLBP and examines the potential of novel opioids and other analgesics that may be a useful addition to the treatment options for patients with chronic pain.
Learn More >Physiological responses related to manual therapy (MT) treatment have been investigated over decades using various animal models. However, these studies have not been compiled and their collective findings appraised. The purpose of this scoping review was to assess current scientific knowledge on the physiological responses related to MT and/or simulated MT procedures in animal models so as to act as a resource to better inform future mechanistic and clinical research incorporating these therapeutic interventions. PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, and Index of Chiropractic Literature (ICL) were searched from database inception to August 2019. Eligible studies were: (a) published in English; (b) non-cadaveric animal-based; (c) original data studies; (d) included a form of MT or simulated MT as treatment; (e) included quantification of at least one delivery parameter of MT treatment; (f) quantification of at least one physiological measure that could potentially contribute to therapeutic mechanisms of action of the MT. MT studies were categorized according to three main intervention types: (1) mobilization; (2) manipulation; and (3) massage. Two-phase screening procedures were conducted by a pair of independent reviewers, data were extracted from eligible studies and qualitatively reported. The literature search resulted in 231 articles of which 78 met inclusion criteria and were sorted by intervention type. Joint mobilization induced changes in nociceptive response and inflammatory profile, gene expression, receptor activation, neurotransmitter release and enzymatic activity. Spinal manipulation produced changes in muscle spindle response, nocifensive reflex response and neuronal activity, electromyography, and immunologic response. Physiological changes associated with massage therapy included autonomic, circulatory, lymphatic and immunologic functions, visceral response, gene expression, neuroanatomy, function and pathology, and cellular response to simulated massage. Pre-clinical research supports an association between MT physiological response and multiple potential short-term MT therapeutic mechanisms. Optimization of MT delivery and/or treatment efficacy will require additional preclinical investigation in which MT delivery parameters are controlled and reported using pathological and/or chronic pain models that mimic neuromusculoskeletal conditions for which MT has demonstrated clinical benefit.
Learn More >Sex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex.
Learn More >The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61-70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway.
Learn More >Fibromyalgia (FM) is a chronic pain syndrome, and alexithymia, which is a condition that is characterised by deficits in emotional self-awareness, is highly prevalent among individuals with FM. Insecure attachment styles and inadequate parental care appear to play an important role in the onset and maintenance of both alexithymia and chronic pain. Therefore, the present study aimed to examine the associations between attachment styles, parental bonding, and alexithymia among patients with FM and healthy controls (HC).
Learn More >Burning mouth syndrome (BMS) is classified into idiopathic orofacial pain conditions. Although central and peripheral neuropathic mechanisms are believed to be involved, the etiology remains to be fully elucidated. The present study examined temporal brain responses to an ongoing hot stimulus to investigate the pain modulating system in patients with BMS. The thermal stimulation sequence comprised baseline (32°C, 40 s) to warm (40°C, 32 s) to baseline (32°C, 40 s) to hot (49°C, 32 s), which was repeated four times using a Peltier thermode. These warm and hot stimuli were applied on the right palm and right lower lip in two separate sessions. Functional magnetic resonance imaging data were acquired by recording echo-planar images with a block design. Brain activity induced by purely hot stimulation (49°C vs. 40°C) applied to the palm was more pronounced than that induced by lip stimulation and in patients with BMS compared with controls. Comparison of brain activity between the first 16 s and second 16 s of the stimulus revealed pronounced time-dependent facilitation in patients with BMS during lip stimulation. These findings indicate that the pain modulating system in patients with BMS is dysregulated and that the brain in BMS is highly sensitized to pain information originating from the trigeminal system.
Learn More >Chronic pain in later life is a worldwide problem. In younger patients, chronic pain affects life satisfaction negatively; however, it is unknown whether this outcome will extend into old age.
Learn More >Cerebrospinal fluid (CSF) and brain tissue sodium levels increase during migraine. However, little is known regarding the underlying mechanisms of sodium homeostasis disturbance in the brain during the onset and propagation of migraine. Exploring the cause of sodium dysregulation in the brain is important, since correction of the altered sodium homeostasis could potentially treat migraine. Under the hypothesis that disturbances in sodium transport mechanisms at the blood-CSF barrier (BCSFB) and/or the blood-brain barrier (BBB) are the underlying cause of the elevated CSF and brain tissue sodium levels during migraines, we developed a mechanistic, differential equation model of a rat's brain to compare the significance of the BCSFB and the BBB in controlling CSF and brain tissue sodium levels. The model includes the ventricular system, subarachnoid space, brain tissue and blood. Sodium transport from blood to CSF across the BCSFB, and from blood to brain tissue across the BBB were modeled by influx permeability coefficients and , respectively, while sodium movement from CSF into blood across the BCSFB, and from brain tissue to blood across the BBB were modeled by efflux permeability coefficients and , respectively. We then performed a global sensitivity analysis to investigate the sensitivity of the ventricular CSF, subarachnoid CSF and brain tissue sodium concentrations to pathophysiological variations in , , and . Our results show that the ventricular CSF sodium concentration is highly influenced by perturbations of , and to a much lesser extent by perturbations of . Brain tissue and subarachnoid CSF sodium concentrations are more sensitive to pathophysiological variations of and than variations of and within 30 min of the onset of the perturbations. However, is the most sensitive model parameter, followed by and , in controlling brain tissue and subarachnoid CSF sodium levels within 3 h of the perturbation onset.
Learn More >People with chronic neck pain have impaired proprioception (i.e., sense of neck position). It is unclear whether this impairment involves disruptions to the proprioceptive representation in the brain, peripheral factors, or both. Implicit motor imagery tasks, namely left/right judgements of body parts, assess the integrity of the proprioceptive represention. Previous studies evaluating left/right neck judgements in people with neck pain are conflicting. We conducted a large online study to comprehensively address whether people with neck pain have altered implicit motor imagery performance.
Learn More >Pain can be both a cause and a consequence of sleep deficiency. This bidirectional relationship between sleep and pain has important implications for clinical management of patients, but also for chronic pain prevention and public health more broadly. The review that follows will provide an overview of the neurobiological evidence of mechanisms thought to be involved in the modulation of pain by sleep deficiency, including the opioid, monoaminergic, orexinergic, immune, melatonin, and endocannabinoid systems; the hypothalamus-pituitary-adrenal axis; and adenosine and nitric oxide signaling. In addition, it will provide a broad overview of pharmacological and non-pharmacological approaches for the management of chronic pain comorbid with sleep disturbances and for the management of postoperative pain, as well as discuss the effects of sleep-disturbing medications on pain amplification.
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