OBJECTIVE: Patients with chronic neuropathic pain (CNP) have a higher incidence to develop depression. However, its pathogenesis has not yet been fully elucidated. Here we aimed to investigate the role of inflammatory cytokines in CNP-related anhedonia, which is a core symptom of depression, and to explore the effects of ketamine and parecoxib on pain and anhedonia. METHODS: A rat model of spared nerve injury (SNI) was constructed to mimic CNP. Hierarchical cluster analysis of sucrose preference test (SPT) was applied to classify the SNI rats into anhedonia susceptible and unsusceptible. Inflammatory cytokines in medial prefrontal cortex (mPFC) of brain, serum and L2–5 spinal cord were measured. Moreover, effects of ketamine or parecoxib on mechanical withdrawal test (MWT) and SPT in anhedonia susceptible rats were detected. RESULTS: Tumor necrosis factor (TNF)-α was increased in mPFC, serum and and spinal cord of anhedonia susceptible rats. Furthermore, anhedonia susceptible and unsusceptible rats both increased the interleukin (IL)-1β level in mPFC, serum and spinal cord. IL-6 was altered in serum and spinal cord, but not in mPFC. IL-10 was significantly altered in mPFC and serum, but not in spinal cord. Additionally, ketamine treatment significantly attenuated the decreased results of MWT and SPT in anhedonia susceptible rats, and that parecoxib significantly improved the MWT score, but failed to alter the result of SPT. CONCLUSION: These findings suggest that abnormalities in inflammatory cytokines confer susceptible to anhedonia in a rat model of SNI. Ketamine, a fast-acting antidepressant, has pharmacological benefits to alleviate pain and anhedonia symptoms.
Anhedonia ; Animals ; Brain ; Cytokines ; Depression ; Humans ; Incidence ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Ketamine ; Models, Animal ; Neuralgia ; Neurogenic Inflammation ; Prefrontal Cortex ; Rats ; Spinal Cord ; Sucrose ; Tumor Necrosis Factor-alpha

Epiduroscopy is defined as a percutaneous, minimally invasive endoscopic investigation of the epidural space. Periduroscopy is currently used mainly as a diagnostic tool to directly visualize epidural adhesions in patients with failed back surgery syndrome (FBSS), and as a therapeutic action in patients with low back pain by accurately administering drugs, releasing inflammation, washing the epidural space, and mechanically releasing the scars displayed. Considering epiduroscopy a minimally invasive technique should not lead to underestimating its potential complications. The purpose of this review is to summarize and explain the mechanisms of the side effects strictly related to the technique itself, leaving aside complications considered typical for any kind of extradural procedure (e.g. adverse reactions due to the administration of drugs or bleeding) and not fitting the usual concept of epiduroscopy for which the data on its real usefulness are still lacking. The most frequent complications and side effects of epiduroscopy can be summarized as non-persistent post-procedural low back and/or leg discomfort/pain, transient neurological symptoms (headache, hearing impairment, paresthesia), dural puncture with or without post dural puncture headache (PDPH), post-procedural visual impairment with retinal hemorrhage, encephalopathy resulting in rhabdomyolysis due to a dural tear, intradural cyst, as well as neurogenic bladder and seizures. We also report for first time, to our knowledge, a case of symptomatic pneumocephalus after epiduroscopy, and try to explain the reason for this event and the precautions to avoid this complication.
Brain Diseases ; Cicatrix ; Epidural Space ; Failed Back Surgery Syndrome ; Hearing Loss ; Humans ; Inflammation ; Leg ; Low Back Pain ; Paresthesia ; Pharmaceutical Preparations ; Pneumocephalus ; Post-Dural Puncture Headache ; Punctures ; Retinal Hemorrhage ; Rhabdomyolysis ; Seizures ; Tears ; Tissue Adhesions ; Urinary Bladder, Neurogenic ; Vision Disorders

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.
Action Potentials ; physiology ; Animals ; Disease Models, Animal ; Female ; Ganglia, Sympathetic ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Hyperalgesia ; etiology ; Ligation ; adverse effects ; Macrophages ; pathology ; Male ; Neurogenic Inflammation ; etiology ; Pain ; etiology ; pathology ; Patch-Clamp Techniques ; Peripheral Nerve Injuries ; complications ; Rats ; Rats, Sprague-Dawley ; Receptors, Antigen, T-Cell, alpha-beta ; metabolism

Botulinum toxin (BoNT) injections have been used not only in the field of cosmetic surgery such as forehead and eye wrinkle treatment but also in the treatment of chronic migraine, dystonia, spasticity, temporomandibular disorders (TMD). BoNT injections are the only approved therapies to date for prophylactic treatment of chronic migraine patients. Unlike the previously known paralysis of motor neurons, the mechanism of action for migraine is to block the release of non-cholinergic neurotransmitters such as substance P, CGRP, and glutamate, which are associated with peripheral sensitization and neurogenic inflammation in the sensory nerve, it is hypothesized that the signal is blocked. This review focuses on the analgesic effects of BoNT and suggests the direction for the development of injection methods for chronic migraine patients.
Botulinum Toxins* ; Dystonia ; Forehead ; Glutamic Acid ; Headache Disorders ; Humans ; Migraine Disorders* ; Motor Neurons ; Muscle Spasticity ; Neurogenic Inflammation ; Neurotransmitter Agents ; Paralysis ; Substance P ; Surgery, Plastic ; Temporal Lobe* ; Temporomandibular Joint Disorders

Toluene diisocyanate (TDI) is the most important cause of occupational asthma (OA), and various pathogenic mechanisms have been suggested. Of these mechanisms, neurogenic inflammation is an important inducer of airway inflammation. Transient receptor potential melastatin 8 (TRPM8) is a well-established cold-sensing cation channel that is expressed in both neuronal cells and bronchial epithelial cells. A recent genome-wide association study of TDI-exposed workers found a significant association between the phenotype of TDI-induced OA and the single-nucleotide polymorphism rs10803666, which has been mapped to the TRPM8 gene. We hypothesized that TRPM8 located in airway epithelial cells may be involved in the pathogenic mechanisms of TDI-induced OA and investigated its role. Bronchial epithelial cells were treated with TDI in a dose- and time-dependent manner. The expression levels of TRPM8 mRNA and protein were determined by quantitative real-time polymerase chain reaction and western blotting. TDI-induced morphological changes in the cells were evaluated by immunocytochemistry. Alterations in the transcripts of inflammatory cytokines were examined in accordance with TRPM8 activation by TDI. TRPM8 expression at both the mRNA and protein levels was enhanced by TDI in airway epithelial cells. TRPM8 activation by TDI led to significant increases in the mRNA of interleukin (IL)-4, IL-13, IL-25 and IL-33. The increased expression of the cytokine genes by TDI was partly attenuated after treatment with a TRPM8 antagonist. TDI exposure induces increased expression of TRPM8 mRNA in airway epithelial cells coupled with enhanced expression of inflammatory cytokines, suggesting a novel role of TRPM8 in the pathogenesis of TDI-induced OA.
Asthma, Occupational ; Blotting, Western ; Cytokines ; Epithelial Cells* ; Genome-Wide Association Study ; Immunohistochemistry ; Inflammation* ; Interleukin-13 ; Interleukin-33 ; Interleukins ; Neurogenic Inflammation ; Neurons ; Phenotype ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Toluene 2,4-Diisocyanate* ; Toluene*

Complex regional pain syndrome (CRPS) is a chronic painful, limb-confined condition with autonomic and inflammatory characteristics. Although the exact cause is still poorly understood, facilitated neurogenic inflammation, pathologic sympathetic-afferent coupling, and maladaptive neuroplasticity of CNS are suggested as major pathophysiology of CRPS. While acute CRPS may resolve with good prognosis, chronic CRPS is likely to continue painful condition, thus it is recommended to start early management with comprehensive, multidisciplinary intervention including physical and occupational therapy. It still lacks of studies regarding CRPS after stroke which applied new diagnostic criteria, although it was established in the year of 2004. Therefore, further researches are needed regarding the CRPS after stroke using new diagnostic criteria.
Chronic Pain ; Neuralgia ; Neurogenic Inflammation ; Neuronal Plasticity ; Occupational Therapy ; Prognosis ; Stroke*

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease.
Adhesives ; Apoptosis ; Autoimmunity ; Biomarkers ; Cadherins ; Chondroitin Sulfates ; Cystitis ; Cytokines ; Epithelium ; Gene Expression ; Homeostasis ; Inflammation ; Lower Urinary Tract Symptoms ; Mast Cells ; Neurogenic Inflammation ; Nocturia ; Phenotype ; Population Characteristics* ; Tight Junctions ; Urinary Bladder ; Urinary Bladder Diseases ; Urinary Tract Infections ; Uroplakins

We report on a case of limited form of granulomatosis with polyangiitis (GPA) with pituitary involvement which presented with central diabetes insipidus. This rare form of GPA has not been reported in Korea. The patient presented with fever, headache, productive cough, nasal symptoms, and polyuria. Laboratory data and imaging studies demonstrated inflammatory lesions in nasal sinus and lungs. Pituitary stalk thickening and enhancement were observed on brain magnetic resonance imaging. The histopathology of the lung lesions showed chronic active granulomatous inflammation. Polyuria, hyperosmolar hypernatremia, and decreased urine osmolality which responded to synthetic vasopressin analog were consistent with central diabetes insipidus. Based on the clinical findings and histopathological results, a diagnosis of GPA with pituitary involvement was established. Treatment with desmopressin as well as concurrent glucocorticoids and immunosuppressant resulted in clinical improvement.
Brain ; Cough ; Deamino Arginine Vasopressin ; Diabetes Insipidus, Neurogenic* ; Diagnosis ; Fever ; Glucocorticoids ; Headache ; Humans ; Hypernatremia ; Inflammation ; Korea ; Lung ; Magnetic Resonance Imaging ; Osmolar Concentration ; Pituitary Gland ; Polyuria ; Vasopressins

It is often presumed that apical periodontitis follows total pulp necrosis, and consequently root canal treatment is commonly performed. Periapical lesion development is usually caused by bacteria and its byproduct which irritate pulp, develop pulpitis, and result in necrosis through an irreversible process. Afterwards, apical periodontitis occurs. This phenomenon is observed as an apical radiolucency in radiographic view. However, this unusual case presents a spontaneous healing of periapical lesion, which has developed without pulp necrosis in a vital tooth, through conservative treatment.
Bacteria ; Dental Pulp Cavity ; Dental Pulp Necrosis ; Necrosis ; Neurogenic Inflammation ; Periapical Periodontitis ; Pulpitis ; Tooth

AIMTo explore the physiopathological mechanisms of airway injury and the effect on the airway responsiveness of rat by inhaled sulfur dioxide(SO2).

METHODSSixteen SD male rats were divided randomly into 2 groups (n = 8): the control group and SO2 group. The control group was exposed o pure air. SO2 group was exposed to SO2 of the content 1.0 mg/(m(3) x h) 6h daily for consecutive 3 d. At 4th day, we determined the airway responsiveness, collected the bronchoalveolar lavage fluid (BALF), plasma and lung tissue. Then we counted the total cellular score in BALF, measured the plasma SP content and made the immunohistochemistry staining on the lung tissue (HE and SP methods).

RESULTSCompared with the control group, the total cellular score in BALF and plasma SP content in SO2 group's increased significantly ( P < 0.01). HE staining showed there were a great deal of inflammatory cells infiltration under the tunica mucosa bronchiorum; and SP immunohistochemistry staining indicated there were significant changes in numbers of SP-IR positive fibers of SO2group.

CONCLUSIONExposure to low concentration of SO2 would injure healthy rat's airway, and induce airway hyperresponsiveness, neurogenic inflammation is one of its critical pathophysiological mechanisms.

Air Pollutants ; adverse effects ; Animals ; Asthma ; chemically induced ; Bronchi ; drug effects ; innervation ; physiopathology ; Bronchial Hyperreactivity ; chemically induced ; physiopathology ; Bronchitis ; chemically induced ; Bronchoalveolar Lavage Fluid ; cytology ; Male ; Nerve Fibers ; drug effects ; physiology ; Neurogenic Inflammation ; chemically induced ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substance P ; blood ; Sulfur Dioxide ; adverse effects