Chronic Primary Pain Research Articles

Urinary TNF-α as a potential biomarker for chronic primary low back pain.

Over two thirds of individuals with low back pain (LBP) may experience recurrent or persistent symptoms in the long term. Yet, current data do not allow to predict who will develop chronic low back pain and who will recover from an acute episode. Elevated serum levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) have been associated with poor recovery and persistent pain following an acute episode of LBP. Inflammatory cytokines may also mediate mechanisms involved in nociplastic pain, and thus, have significant implications in chronic primary low back pain (CPLBP). This study aimed to investigate the potential of urinary TNF-α levels for predicting outcomes and characterizing clinical features of CPLBP patients. Twenty-four patients with CPLBP and 24 sex- and age-matched asymptomatic controls were recruited. Urinary TNF-α concentrations were measured at baseline and after 4 weeks, during which CPLBP patients underwent spinal manipulative therapy (SMT). Concentrations of TNF-α were found to be elevated in baseline urine samples of CPLBP patients compared to asymptomatic controls. Moreover, these values differed among patients depending on their pain trajectory. Patients with persistent pain showed higher levels of TNF-α, when compared to those with episodic CPLBP. Furthermore, baseline TNF-α concentrations and their changes after 4 weeks predicted alterations in pain intensity and disability following SMT in patients with CPLBP. These findings warrant further research on the potential use of urinary TNF-α concentrations as a prognostic biomarker for CPLBP.

Prevalence of chronic primary pain in pediatric patients. Ó?Dr. Eduardo LiceagaÓ� General Hospital of Mexico

Prevalence of chronic primary pain in pediatric patients. Ó?Dr. Eduardo LiceagaÓ� General Hospital of Mexico

Functional neurological disorder is common in patients attending chronic pain clinics.

Chronic pain is a common comorbidity in those with functional neurological disorder (FND); however, the prevalence and characteristics of FND in those with chronic pain is unknown. A retrospective electronic records review was made of consecutive new patients attending a chronic pain clinic of a regional service. Clinical features, medication for and outcome of chronic pain, any lifetime diagnoses of functional disorders, FND, and psychiatric disorders, and undiagnosed neurological symptoms were recorded. Of 190 patients attending the chronic pain clinic, 32 (17%) had a lifetime diagnosis of FND and an additional 11 (6%) had undiagnosed neurological symptoms. Pain patients with comorbid FND were more likely to have chronic primary pain (88% with FND, 44% without FND, p < 0.0001), widespread chronic primary pain (53%, 15%, p < 0.00001), and depression (84%, 52%, p < 0.005) and less likely to have a pain-precipitating event (19% vs. 56%, p < 0.001). However, there was no significant difference between these patients in opiate prescription, benzodiazepine prescription, or pain outcome. This first study of FND in a chronic pain patient population found a remarkably high prevalence of FND (17%) and is possibly an underestimation. The size of the overlap indicates that FND and chronic pain research fields are likely to have a lot to learn from each other.

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP.

Descending serotonergic modulation from rostral ventromedial medulla to spinal trigeminal nucleus is involved in experimental occlusal interference-induced chronic orofacial hyperalgesia

BackgroundDental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI).MethodsExpressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM.ResultsUpregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats.ConclusionsThese results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.Graphical

How Treatment Motivation Predicts Favorable Outcomes in Interdisciplinary Multimodal Pain Treatment Among Patients with Chronic Primary Pain

As motivation for psychological treatment at intake has been shown to predict favorable outcomes after an inpatient stay, this study aimed to further characterize the different components of psychological treatment motivation that predict favorable treatment outcomes. 294 inpatients with chronic primary pain participating in an interdisciplinary multimodal pain treatment in a tertiary psychosomatic university clinic completed a battery of psychological questionnaires at intake and discharge. Treatment motivation was assessed at intake using the scales of the FPTM-23 questionnaire, while pain intensity, pain interference, anxiety, and depression were assessed both at intake and discharge. After treatment, pain intensity, pain interference, anxiety, and depression were significantly reduced. While higher levels on the FPTM-23 scale of suffering predicted smaller decreases in anxiety after treatment, higher scores on the scale of hope, i.e., lower levels of hopelessness, predicted lower levels of pain interference, anxiety, and depression after treatment. None of the scales of treatment motivation predicted pain intensity levels after treatment. Above and beyond providing symptom relief, reducing hopelessness and fostering hope regarding the treatment process and outcome might help clinicians treat patients with chronic primary pain more effectively.

From non-specific low back pain to chronic primary musculoskeletal low back pain: the evolving concept

Background: Low back pain (LBP) for many years is considered one of the most common conditions causing work absenteeism and long-term disability, with important implications for public health systems and economies. Pain generators of LBP are various, being distinguished specific and non-specific causative mechanisms. The term “non-specific” LBP remains ambiguous as potential sources of pain are supposed to be muscles or joints, but supplementary investigations do not correlate enough to explain the pain intensity and disability. The nociceptive and/or neuropathic mechanisms characteristic for acute pain tend to be influenced by central sensitization while pain chronification occurs, leading to new descriptor as nociplastic pain. Chronic low back pain, considered mostly non-specific, was mechanistically referred to primary musculoskeletal low back pain, the concept introduced in the new ICD-11 classification. The process of acceptance by the scientific medical community raised debates and discussions. The aim of the study was to analyze the evolving concept of non-specific low back pain to chronic primary musculoskeletal low back pain. A narrative literature review was carried out. Conclusions: The term non-specific low back pain is used when the pain generators have not been accurately determined or cannot fully explain the existing symptomatology. Chronic primary musculoskeletal low back pain is better explained by central sensitization mechanisms and altered nociception, named nociplastic pain. Because of raised ambiguities regarding this concept further studies are expected to shed light on the problem.

EEG assessment of brain dysfunction for patients with chronic primary pain and depression under auditory oddball task.

In 2019, the International Classification of Diseases 11th Revision International Classification of Diseases (ICD-11) put forward a new concept of "chronic primary pain" (CPP), a kind of chronic pain characterized by severe functional disability and emotional distress, which is a medical problem that deserves great attention. Although CPP is closely related to depressive disorder, its potential neural characteristics are still unclear. This paper collected EEG data from 67 subjects (23 healthy subjects, 22 patients with depression, and 22 patients with CPP) under the auditory oddball paradigm, systematically analyzed the brain network connection matrix and graph theory characteristic indicators, and classified the EEG and PLI matrices of three groups of people by frequency band based on deep learning. The results showed significant differences in brain network connectivity between CPP patients and depressive patients. Specifically, the connectivity within the frontoparietal network of the Theta band in CPP patients is significantly enhanced. The CNN classification model of EEG is better than that of PLI, with the highest accuracy of 85.01% in Gamma band in former and 79.64% in Theta band in later. We propose hyperexcitability in attentional control in CPP patients and provide a novel method for objective assessment of chronic primary pain.

Does Diagnostic Certainty Matter?: Pain-Related Stigma in Adolescents with Juvenile Idiopathic Arthritis.

Childhood chronic pain conditions are common and vulnerable to stigma. Adolescents with chronic primary pain experience diagnostic uncertainty and describe pain-related stigma experiences across multiple social contexts. Juvenile idiopathic arthritis (JIA) is a childhood autoimmune, inflammatory condition with associated chronic pain, but with well-defined diagnostic criteria. The current study examined pain-related stigma experiences in adolescents with JIA. Four focus groups of 3-7 adolescents with JIA (N = 16), ages 12-17 (Mage = 15.42, SD = 1.82), and parents (N = 13) were conducted to examine experiences of, and reaction to, pain-related stigma. Patients were recruited from an outpatient pediatric rheumatology clinic. Focus group length ranged from 28 to 99 minutes long. Two coders used directed content analysis resulting in 82.17% inter-rater level of agreement. Adolescents with JIA described pain-related stigma experiences predominantly from school teachers and peers, and less from medical providers (e.g., school nurses), and family members after a diagnosis. The primary categories that emerged were (1) Felt Stigma, (2) Internalized Stigma, (3) Anticipatory Stigma/Concealment, and (4) Contributions to Pain-Related Stigma. A common experience of pain-related stigma was the perception by others that the adolescent was too young to have arthritis. In common with adolescents with unexplained chronic pain, our findings indicate that adolescents with JIA experience pain-related stigma in certain social contexts. Diagnostic certainty may contribute to greater support among medical providers and within families. Future research should investigate the impact of pain-related stigma across childhood pain conditions.

Improvements in pain coping predict treatment success among patients with chronic primary pain

ObjectiveGiven the increasing incidence and prevalence of chronic pain, effective treatments for chronic pain are needed. This study aimed to investigate the role of cognitive and behavioral pain coping regarding the prediction of treatment outcomes among inpatients with chronic primary pain participating in an interdisciplinary multimodal treatment program. MethodsAt intake and discharge, 500 patients with chronic primary pain completed questionnaires on pain intensity, pain interference, psychological distress, and pain processing. ResultsPatients' symptoms, cognitive and behavioral pain coping improved significantly after treatment. Similarly, separate cognitive and behaviroal coping skills improved significantly after treatment. Hierarchical linear models revealed no significant associations of pain coping with reductions in pain intensity. Whereas the overall level and improvements in cognitive pain coping predicted reductions in pain interference and psychological distress, the overall level and improvements in behavioral pain coping were associated with reductions in pain interference alone. DiscussionSince pain coping seems to influence both pain interference and psychological distress, improving cognitive and behavioral pain coping during an interdisciplinary multimodal pain treatment seems to be a key component in the successful treatment of inpatients with chronic primary pain, enabling them to function better physically and mentally despite their chronic pain. Clinically, it might be worth fostering and exercising cognitive restructuring as well as action planning in treatment to reduce both pain interference and psychological distress levels post-treatment. In addition, practicing relaxation techniques might help reduce pain interference post-treatment, whereas making experiences of personal competence might help reduce psychological distress post-treatment.

Clinical differences in a multidisciplinary pediatric pain unit between primary and secondary chronic pain.

Chronic pain affects an important part of the pediatric population in developed countries. secondary chronic pain (SCP) can have a well-defined medical cause, but primary chronic pain (PCP) can have an unknown etiology. In Spain, there is as yet no information on the clinical differences between patients treated in multidisciplinary units. Retrospective analysis of the clinical records of patients seen in 2018 at the Children's Chronic Pain Unit in University La Paz Hospital. A total of 92 patients were included, (age between 3 and 19 years), with a mean age of 12.4 (SD = 4.1) years, mostly female (55%), with a mean duration of pain of 11.3 (SD = 10.4) months. A comparison of patients with PCP (n = 31) and SCP (n = 61) showed that both groups, on average, presented intense pain (X = 5.9; SD = 2.2; range = 0-10), with similar duration and functional repercussions, although PCP was less likely to be associated with neuropathic descriptors than SCP (p = 0.040), and was more extensive (p < 0.001). Both groups received similar treatment, based on rehabilitation, psychotherapy, invasive techniques and analgesic medication, although patients in the PCP group received less analgesic medication (gabapentinoids and opioids) than the SCP (p = 0.011). Patients treated in a multidisciplinary Child Pain Unit for PCP or SCP present a very similar clinical profile, though with differences in the number and type of analgesic drugs used. This shows the importance of etiologic diagnosis for adequate pharmacological treatment.

War experiences and relationship problems predict pain sensitivity cross-sectionally among patients with chronic primary pain

Background: Most patients suffering from chronic pain are more susceptible to pain and pressure due to higher pain sensitivity. Since psychosocial factors play a central role in developing and maintaining chronic pain, investigating associations between pain sensitivity and psychosocial stressors promises to advance the biopsychosocial understanding of chronic pain. Objectives: We aimed to replicate Studer et al.'s (2016) findings about associations of psychosocial stressors with pain sensitivity in a new sample of patients with chronic primary pain (ICD-11, MG30.0). Methods: A pain provocation test was used on both middle fingers and earlobes to assess pain sensitivity among 460 inpatients with chronic primary pain. Potentially life-threatening accidents, war experiences, relationship problems, certified inability to work, and adverse childhood experiences were assessed as potential psychosocial stressors. Structural equation modeling was used to investigate associations between psychosocial stressors and pain sensitivity. Results: We partially replicated Studer et al.'s findings. Similar to the original study, patients with chronic primary pain showed enhanced pain sensitivity values. Within the investigated group, war experiences (β = 0.160, p < .001) and relationship problems (β = 0.096, p = .014) were associated with higher pain sensitivity. In addition, the control variables of age, sex, and pain intensity also showed a predictive value for higher pain sensitivity. Unlike Studer et al., we could not identify a certified inability to work as a predictor of higher pain sensitivity. Conclusions: This study showed that beyond age, sex, and pain intensity, the psychosocial stressors of war experiences and relationship problems were associated with higher pain sensitivity.

Chronic Pain: Definition/Conception/Classification of Pain

Understanding what pain is necessary to understand the pathomechanisms of chronic pain. The International Association for the Study of Pain (IASP) defines pain as "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage" and its further states that pain is a personal experience, influenced to varying degrees by biological, psychological, and social factors. It also mentions that person learn the concept of the pain through life experiences, and that it does not always play an adaptive role and has a negative impact on our physical, social, and psychological health. In order to classify chronic pain, IASP created a coding system in ICD11 that focuses on chronic secondary pain, which has clear organic factors, and chronic primary pain, which is difficult to explain from the organic aspect alone. When considering pain treatment, it is necessary to consider three pain mechanisms, including nociceptive pain, neuropathic pain, and nociplastic pain, which is a condition in which the patient feels strong pain due to sensitization of the nervous system.

Long-term efficacy of spinal cord stimulation for chronic primary neuropathic pain in the contemporary era: a systematic review and meta-analysis.

Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain. We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS. According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months. SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.

Integration of Acupuncture into UK Healthcare - A NICE Perspective: Why is Acupuncture Now Recommended for Chronic Pain but not for Back Pain or Osteoarthritis

In April 2021, the National Institute for Health and Care Excellence (NICE) published a guideline on chronic pain (NG193) with a recommendation to consider a single course of acupuncture treatment in patients with chronic primary pain. This positive recommendation came after the NICE guideline on low back pain and sciatica (NG59) announced in November 2016, that acupuncture treatment did not work for back pain, having previously recommended it in 2009 (CG88). This article attempts to explain this apparent contradiction in recommendations by tracing the history of acupuncture debates in the NICE guidelines over the last 2 decades.

Chronic Migraine as a Primary Chronic Pain Syndrome and Recommended Prophylactic Therapeutic Options: A Literature Review.

Chronic pain conditions have a high socio-economic impact and represent a burden for patients, and their management is a challenge for healthcare professionals. Chronic migraine is one of the chronic primary headache disorders, which belong to chronic primary pain syndromes as per the new concept of multiple parenting. The aims of this review were to provide an overview of the latest classification systems involving both entities, the epidemiological data, and the currently recommended prophylactic treatment options for chronic migraine. Randomized controlled clinical trials, meta-analyses, real-world data, and review articles were analyzed. Chronic migraine is a prevalent and highly burdensome disease and is associated with high headache-related disability and worsening health-related quality of life. Treatment of chronic migraine includes pharmacological or, in drug-refractory cases, non-pharmacological (e.g., neuromodulatory) approaches. Among pharmacological treatment options, injectable botulinum toxin type A and calcitonin gene-related peptide-targeting human and fully humanized monoclonal antibodies (i.e., eptinezumab, erenumab, fremanezumab, and galcanezumab) are highly recommended in the preventive treatment of chronic migraine. Novel migraine-specific therapies offer a solution for this devastating and difficult-to-treat chronic pain condition.

Motive Satisfaction Among Patients with Chronic Primary Pain: A Replication

We set out to replicate findings of significant (a) reductions in pain, psychological distress, and motivational incongruence (i.e., insufficient motive satisfaction) after interdisciplinary multimodal pain treatment and (b) associations between reductions in motivational incongruence (i.e., improved motive satisfaction) and decreases in psychological distress (Vincent et al., Journal of Clinical Psychology in Medical Settings 28:331–343, 2021). 475 Patients with chronic primary pain completed standardized self-reported questionnaires assessing motivational incongruence, psychological distress, pain intensity, and pain interference at intake and discharge from a tertiary psychosomatic university clinic. We used hierarchical linear models to analyze motivational incongruence’s effects on psychological distress. We partially replicated Vincent et al.’s findings. Significant reductions in pain, psychological distress, and motivational incongruence after treatment were found. Reductions in motivational incongruence were associated with reductions in psychological distress. Similarly, a better motive satisfaction mediated the relationship between pain interference and psychological distress. Our findings show that reducing motivational incongruence may be a key component of treating chronic primary pain; we recommend to assess and target motivational incongruence to improve interdisciplinary multimodal pain treatment.

Balancing the evidence: An update on analgesic use in rheumatic and musculoskeletal diseases

Pain management has been a challenging issue for people living with rheumatic and musculoskeletal diseases (RMDs) and health professionals for decades. Pharmacological treatments remain a core element of pain management of inflammatory arthritis and osteoarthritis. Yet balancing the benefits/harms in pain management within RMDs can be difficult to navigate due to limited effective options, and emerging adverse events in a population where individual risk is important to consider due to patient multimorbidity, immunosuppression and polypharmacy. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) analgesics are widely used among RMD patients, however both classes of drugs have been associated with new safety concerns in the last two decades. Perhaps as a result in combination with multifactorial influences, opioid prescribing has increased from the 2000s–2010s in the majority of RMD focussed studies, accompanied with a rising trend of long-term opioid use, despite limited evidence on efficacy. Gabapentinoids have also shown increasing trends more recently, despite an unclear role in chronic pain management for RMDs within current guidelines. Antidepressants are recommended as the first line of pharmacological treatment of chronic primary pain (e.g., fibromyalgia) by the latest National Institute for Health and Care Excellence (NICE) guideline released in April 2021. This concise narrative review will discuss pharmacological options for pain management, based on the latest evidence that includes the main analgesic drug classes: paracetamol, NSAIDs, opioids, antidepressants, and gabapentinoids. We will discuss the efficacy of these analgesics in RMDs and emerging safety concerns to enable more informed shared decisions with patients commencing such medications.

Moving away from medicines: an overview of chronic pain management.

Chronic pain can be debilitating and affects an increasing number of people in the UK due to an ageing population and the rising prevalence of comorbidities. Chronic pain can be primary, where it is not accounted for by another condition, or secondary, where it results from an underlying condition or injury. The National Institute for Health and Care Excellence has published updated guidance on the assessment and management of chronic pain in adults. This article explores the latest recommendations regarding medicines use in chronic primary pain and outlines appropriate non-pharmacological management strategies. It also discusses some of the barriers to implementing chronic pain management interventions, and provides advice for nurses caring for patients who are experiencing this type of pain.

Mechanisms of chiropractic spinal manipulative therapy for patients with chronic primary low back pain: protocol for a mechanistic randomised placebo-controlled trial

IntroductionChronic low back pain (CLBP) is a highly prevalent and disabling condition. Identifying subgroups of patients afflicted with CLBP is a current research priority, for which a classification system based...