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The Journal of Pharmacology and... May 2024The prefrontal cortex (PFC) has justifiably become a significant focus of chronic pain research. Collectively, decades of rodent and human research have provided strong... (Review)
Review
The prefrontal cortex (PFC) has justifiably become a significant focus of chronic pain research. Collectively, decades of rodent and human research have provided strong rationale for studying the dysfunction of the PFC as a contributing factor in the development and persistence of chronic pain and as a key supraspinal mechanism for pain-induced comorbidities such as anxiety, depression, and cognitive decline. Chronic pain alters the structure, chemistry, and connectivity of PFC in both humans and rodents. In this review, we broadly summarize the complexities of reported changes within both rodent and human PFC caused by pain and offer insight into potential pharmacological and nonpharmacological approaches for targeting PFC to treat chronic pain and pain-associated comorbidities. SIGNIFICANCE STATEMENT: Chronic pain is a significant unresolved medical problem causing detrimental changes to physiological, psychological, and behavioral aspects of life. Drawbacks of currently approved pain therapeutics include incomplete efficacy and potential for abuse producing a critical need for novel approaches to treat pain and comorbid disorders. This review provides insight into how manipulation of prefrontal cortex circuits could address this unmet need of more efficacious and safer pain therapeutics.
Topics: Prefrontal Cortex; Humans; Animals; Chronic Pain; Pain
PubMed: 38702195
DOI: 10.1124/jpet.123.002046 -
Current Opinion in Supportive and... Sep 2023Chronic pain is poorly treated with many developing disabling comorbidities such as anxiety, depression and insomnia. Considerable evidence supports the idea that pain... (Review)
Review
PURPOSE OF REVIEW
Chronic pain is poorly treated with many developing disabling comorbidities such as anxiety, depression and insomnia. Considerable evidence supports the idea that pain and anxiodepressive disorders share a common neurobiology and can mutually reinforce, which has significant long-term implications as the development of comorbidities leads to poorer treatment outcomes for both pain and mood disorders. This article will review recent advances in the understanding of the circuit basis for comorbidities in chronic pain.
RECENT FINDINGS
A growing number of studies have aimed to determine the mechanisms underlying chronic pain and comorbid mood disorders by using modern viral tracing tools for precise circuit manipulation with optogenetics and chemogenetics. These have revealed critical ascending and descending circuits, which advance the understanding of the interconnected pathways that modulate the sensory dimension of pain and the long-term emotional consequences of chronic pain.
SUMMARY
Comorbid pain and mood disorders can produce circuit-specific maladaptive plasticity; however, several translational issues require addressing to maximise future therapeutic potential. These include the validity of preclinical models, the translatability of endpoints and expanding analysis to the molecular and system levels.
Topics: Humans; Chronic Pain; Comorbidity; Anxiety; Emotions
PubMed: 37096597
DOI: 10.1097/SPC.0000000000000650 -
European Journal of Anaesthesiology May 2024Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. (Observational Study)
Observational Study
BACKGROUND
Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors.
OBJECTIVE
To find predictive factors for CPSP in an international survey.
DESIGN
Observational study.
SETTING
Multicentre European prospective observational trial.
PATIENTS
Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA).
METHOD
Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview.
MAIN OUTCOME MEASURE
The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery.
RESULTS
A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified.
CONCLUSION
Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research.
TRIAL REGISTRATION
clinicaltrials.gov ID: NCT03834922.
Topics: Female; Humans; Breast Neoplasms; Chronic Pain; Endometriosis; Neuralgia; Pain, Postoperative; Quality of Life; Surveys and Questionnaires; Male
PubMed: 38414426
DOI: 10.1097/EJA.0000000000001974 -
Nutritional Neuroscience May 2024The growing global burden of pain is gradually expanding from the medical field to public health. Dietary inflammatory potential correlates with inflammatory markers,...
OBJECTIVES
The growing global burden of pain is gradually expanding from the medical field to public health. Dietary inflammatory potential correlates with inflammatory markers, and inflammation is one of the main mechanisms of pain.
METHODS
This study explored the association between dietary inflammatory index (DII) and pain from the NHANES database on DII and pain (neck pain, low back pain, joint pain, and headache or migraine) using logistic regression and stratified analysis.
RESULTS
The results show a stronger association between DII and joint pain (Q4 of DII adjusted-OR = 1.23, 95% CI = 1.08-1.40, = 0.003) and headache or migraine (Q4 of DII adjusted-OR = 1.31, 95% CI = 1.15-1.48, < 0.001), but no association is found in neck pain (Q4 of DII adjusted-OR = 1.03, 95% CI = 0.89-1.20, = 0.65) and low back pain (Q4 of DII adjusted-OR = 1.04, 95% CI = 0.92-1.17, = 0.54). After stratifying the data according to demographics, differences in the relationship between DII and pain are found at different levels of the population.
DISCUSSION
This study identifies high DII as a risk factor for joint pain and headache or migraine.
Topics: Adult; Humans; Nutrition Surveys; Low Back Pain; Neck Pain; Diet; Inflammation; Headache; Arthralgia; Migraine Disorders
PubMed: 37254575
DOI: 10.1080/1028415X.2023.2218122 -
Biochemical Pharmacology Sep 2023Perineural invasion (PNI) is the process through which tumors invade and interact with nerves. The dynamic changes in the nerves caused by PNI may induce disturbing... (Review)
Review
Perineural invasion (PNI) is the process through which tumors invade and interact with nerves. The dynamic changes in the nerves caused by PNI may induce disturbing symptoms. PNI-related cancer pain in neuro-rich tumors has attracted much attention because the occurrence of tumor-induced pain is closely related to the invasion of nerves in the tumor microenvironment. PNI-related pain might indicate the occurrence of PNI, guide the improvement of treatment strategies, and predict the unresectability of tumors and the necessity of palliative care. Although many studies have investigated PNI, its relationship with tumor-induced pain and its common mechanisms have not been summarized thoroughly. Therefore, in this review, we evaluated the relationship between PNI and cancer-associated pain. We showed that PNI is a major cause of cancer-related pain and that this pain can predict the occurrence of PNI. We also elucidated the cellular and molecular mechanisms of PNI-induced pain. Finally, we analyzed the possible targets for alleviating PNI-related pain or combined antitumor and pain management. Our findings might provide new perspectives for improving the treatment of patients with malignant tumors.
Topics: Humans; Cancer Pain; Pain; Tumor Microenvironment; Neoplasms
PubMed: 37481133
DOI: 10.1016/j.bcp.2023.115692 -
Deutsches Arzteblatt International Jul 2023Chronic primary pelvic pain syndrome in men (CPPPSm) can be associated with urogenital pain, urinary symptoms, sexual dysfunction, and emotional disturbance. Its... (Review)
Review
BACKGROUND
Chronic primary pelvic pain syndrome in men (CPPPSm) can be associated with urogenital pain, urinary symptoms, sexual dysfunction, and emotional disturbance. Its clinical heterogeneity and incompletely understood pathogenesis make it more difficult to treat. This article is intended to familiarize the reader with basic aspects of the manifestations, pathophysiology, diagnostic evaluation, differential diagnosis, and treatment of this condition.
METHODS
This article is based on relevant publications retrieved by a selective search of the literature, including the current guidelines of the European Association of Urology. The features of this disease pertaining to urology, psychosomatic medicine, and pain medicine are illuminated from an interdisciplinary perspective.
RESULTS
Chronic pelvic pain appears to arise through a complex interaction of inflammatory, infectious, neurological, musculoskeletal, and psychosomatic factors. A comprehensive diagnostic work-up should be carried out to evaluate and exclude the numerous differential diagnoses. Treatment strategies are based on the clinical phenotype. Randomized controlled trials have shown that significant relief can be achieved with a variety of drugs and non-pharmacological treatments, selected according to the manifestations of the condition in the individual case. Attention must be paid to treatment-specific adverse effects.
CONCLUSION
The management of patients with CPPPSm should consist of a comprehensive differential diagnostic evaluation and an individually oriented treatment strategy.
Topics: Humans; Male; Chronic Pain; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Pelvic Pain; Phenotype
PubMed: 36922749
DOI: 10.3238/arztebl.m2023.0036 -
Current Opinion in Urology Mar 2024Chronic pelvic pain is much of a burden to those who suffer from it. Additionally, in many patients medical doctors, such as urologists are unable to identify a cause or... (Review)
Review
PURPOSE OF REVIEW
Chronic pelvic pain is much of a burden to those who suffer from it. Additionally, in many patients medical doctors, such as urologists are unable to identify a cause or clear pathology that can explain the pain. Still numerous patients and doctors keep on searching for a cause, focussing particularly on the pelvic organs. Lots of diagnostics and treatment methods are used but often without success. In recent years, we have gained increased insight into the mechanisms of pain and adapted the terminology accordingly.
RECENT FINDINGS
Two aspects of chronic pelvic pain have gained more attention. First, the myofascial aspects, especially the role of the pelvic floor muscles in maintaining the pain and as a therapeutic option. Second, the role of the brain and the psychological aspects intertwine with the pain and its consequences also open up for alternative management options. In terminology chronic pain is now included in the ICD-11, a historical change. Introducing chronic primary pain (no cause found) helps us to look away from the organ and deal with the patient as a whole human being.
SUMMARY
The findings reported here are helpful for your daily practice. Looking from a broad perspective gives the patient the feeling of being seen and heard. Working together in a multidisciplinary team makes your work easier and gives more satisfaction.
VIDEO ABSTRACT
http://links.lww.com/COU/A44.
Topics: Humans; Chronic Pain; Urinary Bladder; Myofascial Pain Syndromes; Pelvic Pain; Pelvis
PubMed: 37823725
DOI: 10.1097/MOU.0000000000001134 -
Glia Oct 2023Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen... (Review)
Review
Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen the suffering of patients with cancer. Reception and transmission of sensory signal receptors, abnormal activation of primary sensory neurons, and activation of glial cells are involved in cancer pain. Therefore, exploring promising therapeutic methods to suppress cancer pain is of great significance. Various studies have found that the use of functionally active cells is a potentially effective way to relieve pain. Schwann cells (SCs) act as small, biologically active pumps that secrete pain-relieving neuroactive substances. Moreover, SCs can regulate the progression of tumor cells, including proliferation and metastasis, through neuro-tumor crosstalk, which emphasizes the critical role of SCs in cancer and cancer pain. The mechanisms by which SCs repair injured nerves and exert analgesia include neuroprotection, neurotrophy, nerve regeneration, neuromodulation, immunomodulation, and enhancement of the nerve-injury microenvironment. These factors may ultimately restore the damaged or stimulated nerves and contribute to pain relief. Strategies for pain treatment using cell transplantation mainly focus on analgesia and nerve repair. Although these cells are in the initial stages of nerve repair and pain, they open new avenues for the treatment of cancer pain. Therefore, this paper discusses, for the first time, the possible mechanism of SCs and cancer pain, and new strategies and potential problems in cancer pain treatment.
Topics: Humans; Cancer Pain; Schwann Cells; Neuroglia; Peripheral Nervous System Diseases; Nerve Regeneration; Pain; Neoplasms
PubMed: 37218574
DOI: 10.1002/glia.24391 -
The Veterinary Clinics of North... Jul 2023Pain recognition, assessment, and management is a primary focus and an integral part of veterinary rehabilitation. Evidence-based pain mitigation protocols will use both... (Review)
Review
Pain recognition, assessment, and management is a primary focus and an integral part of veterinary rehabilitation. Evidence-based pain mitigation protocols will use both pharmacologic tools and nonpharmacologic methods to create a customized, safe, and effective treatment plan. A multimodal, patient-centered approach will allow for the best outcomes for pain relief and improved quality of life.
Topics: Animals; Pain Management; Quality of Life; Pain; Treatment Outcome
PubMed: 37019720
DOI: 10.1016/j.cvsm.2023.02.006 -
The Journal of Pain Dec 2023Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to... (Observational Study)
Observational Study
Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.
Topics: Adult; Humans; Biomarkers; Chronic Pain; Cytokine Receptor gp130; Neuralgia; Nociception; Nociceptive Pain; Pancreatitis, Chronic
PubMed: 37451493
DOI: 10.1016/j.jpain.2023.07.006