Manifestations Of Chronic Pain Research Articles

Gut instinct: Sex differences in the gut microbiome are associated with changes in adolescent nociception following maternal separation in rats.

Adolescent chronic pain is a growing public health epidemic. Our understanding of its etiology is limited; however, several factors can increase susceptibility, often developing in response to an acute pain trigger such as a surgical procedure or mild traumatic brain injury (mTBI), or an adverse childhood experience (ACE). Additionally, the prevalence and manifestation of chronic pain is sexually dimorphic, with double the rates in females than males. Despite this, the majority of pre-clinical pain research focuses on males, leaving a gap in mechanistic understanding for females. Given that emerging evidence has linked the gut microbiome and the brain-gut-immune axis to various pain disorders, we aimed to investigate sex-dependent changes in taxonomic and functional gut microbiome features following an ACE and acute injury as chronic pain triggers. Male and female Sprague Dawley rat pups were randomly assigned to either a maternal separation (MS) or no stress paradigm, then further into a sham, mTBI, or surgery condition. Chronically, the von Frey test was used to measure mechanical nociception, and fecal samples were collected for 16S rRNA sequencing. Animals in the surgery group had an increase in pain sensitivity when compared to mTBI and sham groups, and this was complemented by changes to the gut microbiome. In addition, significant sex differences were identified in gut microbiome composition, which were exacerbated in response to MS. Overall, we provide preliminary evidence for sex differences and ACE-induced changes in bacterial composition that, when combined, may be contributing to heterogeneity in pain outcomes.

Pain as a threat—psychological and phenomenological aspects

Introduction: Pain is a multidimensional experience of injury or threat of future damage, with sensory, cognitive, motivational and emotional aspects. The essence of the pain experience depends on the meaning that the individual gives to pain in a particular situation. Aim: The aim of the article is to analyze and structure the concept of pain as a threat, covering its psychological and phenomenological aspects Materials and Methods: A review and critical analysis of relevant literature have been conducted. Results: It has been established that a predisposing factor for maintaining acute pain and turning it into a chronic one is the expectation (threat) of future harm. The emotional components of the threat of pain (fear and anxiety), as well as the cognitive ones (overvigilance and catastrophizing), have been studied. The assessments of the situation during pain and of the pain-coping resources are the main cognitive mediators that determine the outcome. The perception of pain as a threat provokes fear, anxiety, experiences of insecurity, helplessness, and maladaptive behaviors. Pain-avoiding behavior is in the basis of the stress-diathesis in the manifestation of chronic pain and it predicts future disability. Conclusion: Pain is a threat to the physical and the psychosocial functioning. The assessment of the emotional, cognitive and situational aspects related to pain should be a part of the multidisciplinary approaches to pain management. Manipulating these factors is key to reducing the risk of pain becoming chronic. The application of effective behavioral and cognitive techniques, aimed at increasing the resources for coping with and controlling pain enables patients to continue to function normally in spite of the pain.

Living With a Trifecta of Pain and Cancer With Personal Reflections of COVID-19.

The purpose of preparing this Feature Article was to explore and share my lived experience of living with multiple layers of chronic pain, with a diagnosis of advanced, aggressive and metastasized prostate cancer, and COVID-19. My exploration begins with the manifestations of chronic pain from a bicycling accident, psoriatic arthritis, with cancer treatments and the pain it creates during a panademic has added to the challenges of social distancing, isolation, and medical treatments. As with many patient experiences, we the person as patient outside of health care sometimes struggle to find the right words, the proper sentence structure and as Tamas writes about the expectation of others to provide, “Clean and reasonable scholarship about messy, unreasonable experiences is an exercise in alienation.” I write this while living with extreme chronic pain, continue cancer treatments while the threat and additional anxiety of COVID-19 looms over me. This is my story.

A Step Towards a Better Understanding of Pain Phenotypes: Latent Class Analysis in Chronic Pain Patients Receiving Multimodal Inpatient Treatment.

PurposeThe number of non-responders to treatment among patients with chronic pain (CP) is high, although intensive multimodal treatment is broadly accessible. One reason is the large variability in manifestations of CP. To facilitate the development of tailored treatment approaches, phenotypes of CP must be identified. In this study, we aim to identify subgroups in patients with CP based on several aspects of self-reported health.Patients and MethodsA latent class analysis (LCA) was carried out in retrospective data from 411 patients with CP of different origins. All patients experienced severe physical and psychosocial consequences and were therefore undergoing multimodal inpatient pain treatment. Self-reported measures of pain (visual analogue scales for pain intensity, frequency, and impairment; Pain Perception Scale), emotional distress (Patient Health Questionnaire, PHQ-9; Generalized Anxiety Disorder Scale, GAD-7) and physical health (Short Form Health Survey; SF-8) were collected immediately after admission and before discharge. Instruments assessed at admission were used as input to the LCA. Resulting classes were compared in terms of patient characteristics and treatment outcome.ResultsA model with four latent classes demonstrated the best model fit and interpretability. Classes 1 to 4 included patients with high (54.7%), extreme (17.0%), moderate (15.6%), and low (12.7%) pain burden, respectively. Patients in class 4 showed high levels of emotional distress, whereas emotional distress in the other classes corresponded to the levels of pain burden. While pain as well as physical and mental health improved in class 1, only the levels of depression and anxiety improved in patients in the other groups during multimodal treatment.ConclusionThe specific needs of these subgroups should be taken into account when developing individualized treatment programs. However, the retrospective design limits the significance of the results and replication in prospective studies is desirable.

Psychological and personality differences between male and female veterans in an inpatient interdisciplinary chronic pain program

AbstractIt is projected that by 2033 the Veterans Health Administration (VHA) will have at least a 10% increase in service utilization among female veterans (Yano et al., 2010), with that number rising each year. Research in the general population has revealed mixed but important findings surrounding the experience and manifestation of chronic pain across gender; therefore, it is important to continue exploration of these characteristics in veteran samples to inform chronic pain treatment efforts in the VA system. The current study explored personality and psychological differences between male and female veterans in an inpatient pain rehabilitation program, using the restructured form of the MMPI‐2 (MMPI‐2‐RF). Analyses revealed fewer psychological and personality differences in female and male veterans with chronic pain than expected, with both groups endorsing high levels of somatic and internalizing difficulties and similar psychological processes underlying pain outcomes. Gender differences demonstrating larger effect sizes are explored, and implications for chronic pain treatment are discussed.

Usefulness of knockout mice to clarify the role of the opioid system in chronic pain.

This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

Cerebral metabolic changes and chronic back pain: Study taking into consideration clinical and psychological parameters

The manifestation of chronic pain and psychological impairments are related to alterations of neurotransmitter metabolism in cerebral pain processing regions, e.g., anterior cingular cortex (ACC), insula. Magnetic resonance spectroscopy ((1)H-MRS) enables in vivo quantification of neurotransmitters in the brain and was applied in this study to examine the hypothesized chronic pain-related imbalance between excitatory (glutamatergic) and inhibitory (GABA-ergic) neurotransmitter turnovers in the brain of patients with nonspecific chronic pain. A total of 19 patients with nonspecific chronic (> 3 months) back pain and 19 age- and gender-matched healthy subjects participated in this study. Glutamate and GABA as well as glutamate/GABA ratios were determined in the ACC and insula using (1)H-MRS. Sociodemographic, psychological, and pain-related features were measured with standardized questionnaires. There was a strong variance of glutamate/GABA ratios for both patients and healthy subjects with no significant difference between the two groups. Regression analysis revealed certain significant predictors, such as anxiety as causal variable for reduced glutamate and depression and age as predictors for reduced GABA in ACC. In the patient group, intensity of pain was a significant predictor for glutamate and GABA levels in the insula. Despite the uniform diagnosis of nonspecific chronic back pain, we observed a strong variance of neurotransmitters in cerebral pain processing regions. It is necessary to include psychological as well as clinical parameters (e.g., intensity of pain or depression) for a proper interpretation of neurotransmitter turnovers.

Pharmacokinetics of Compounded Intravenous and Oral Gabapentin in Hispaniolan Amazon Parrots ( Amazona ventralis ).

Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose.

Topical capsaicin for the treatment of neuropathic pain

This review examines neuropathic pain, one of the most common and difficult to treat manifestations of chronic pain. Neuropathic pain follows damage to neural tissue, and can result from numerous causes and manifest in several ways. It can also persist long after any identifiable primary cause resolves. Conventional painkillers produce adequate analgesia in fewer than half of people suffering from neuropathic pain. In some cases, even opiates fail to induce adequate analgesia. Topical capsaicin is an effective treatment for postherpetic neuropathy, painful diabetic neuropathy, osteoarthritis, and rheumatoid arthritis. Nurses should counsel patients about the possibility of a burning sensation during initial treatment. Studies have shown that a single application of 8% capsaicin patch can reduce neuropathic pain for up to 12 weeks.

Schmerzstörungen bei Traumatisierten - neurophysiologische Aspekte und klinische Phänomenologie

This overview portrays the salient physiological mechanisms being involved in the clinical manifestation of chronic pain in traumatized patients. A «hypermnesia-hyperarousal-model» is purported to support the neurophysiologic plausibility of the trauma-pain-relationship. We discuss seven characteristic clinical pain entities which alone or in combination can be found in patients with a previous psychological trauma.

Neurophysiological Correlates of Nociceptive Heterosynaptic Long-Term Potentiation in Humans

Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response in pain perception can be induced in humans using high-frequency electrical stimulation (HFS). The aim of this study was to induce spinal heterosynaptic LTP using HFS and investigate its heterotopic effects on event-related potentials (ERPs) to repeated nonpainful cutaneous stimuli as a possible electrophysiological cortical correlate of sensitization. Twenty-two healthy subjects were randomly assigned to one of the two experimental conditions: HFS and control stimulation. Before and after the stimulation, both conditions received heterotopic mechanical (pinprick) and paired nonpainful electrical test stimuli to quantify and confirm the effects of HFS on the behavioral level. ERPs to paired nonpainful electrical stimulation were measured simultaneously. Conditioning HFS resulted in significant heterotopic effects after 30 min, including increased perceived intensity in response to (pinprick) mechanical and paired nonpainful electrical stimulation compared with control. The paired nonpainful electrical stimuli were accompanied by significantly enhanced responses regarding the ERP N1-P2 peak-to-peak and P300 amplitude compared with control. These findings suggest that HFS is capable of producing heterosynaptic spinal LTP that can be measured not only behaviorally but also using ERPs.

Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia

Fibromyalgia is a prevalent and burdensome disorder characterized by chronic widespread pain and complex comorbid symptoms. To develop better treatments for pain-centered fibromyalgia symptoms, there is still a need for animal models which mimic the features of fibromyalgia patients. In the present study, we have established a fibromyalgia animal model by utilizing a never-before-published pharmacological effect of reserpine. Repeated administration of reserpine (1 mg/kg s.c., once daily, for three consecutive days) causes a significant decrease in the muscle pressure threshold and tactile allodynia, which are sustained for 1 week or more in both male and female rats. This treatment regimen decreases the amount of biogenic amines (dopamine, norepinephrine, and 5-hydroxytryptamine) in the spinal cord, thalamus, and prefrontal cortex, which are deeply involved in pain signal processing. It also significantly increases immobility time in the forced swim test, which is indicative of depression, a common comorbid symptom of fibromyalgia. Pregabalin, duloxetine, and pramipexole significantly attenuated the reserpine-induced decrease in muscle pressure threshold, but diclofenac did not. The validity of the use of this reserpinized animal as a fibromyalgia model is demonstrated from three different aspects, i.e., face validity (manifestation of chronic pain and comorbid symptoms), construct validity (dysfunction of biogenic amine-mediated central nervous system pain control is involved), and predictive validity (similar responses to treatments used in fibromyalgia patients). This animal model is expected to contribute to the better understanding of fibromyalgia pathophysiology and the evaluation of drugs, especially those which would activate biogenic amine system.

Chronic pain syndromes and their treatment II. trigger points

Trigger points are distinct areas of focal hyperirritability which give rise to areas of refered pain in well-defined areas of the musculo-skeletal system, sometimes remote from the point itself and not related to it by anatomically definable pathways. While the vast majority of pain manifestations from trigger points are related to the musculo-skeletal system, this need not be invariably so, as has been demonstrated in two of the cases cited, where injection of trigger points in the neck relieved chronic tinnitus. In all manifestations of chronic pain it is recommended that a diligent search be made for such trigger points.