Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 66
Filter
1.
Experimental Neurobiology ; : 516-528, 2019.
Article in English | WPRIM | ID: wpr-763776

ABSTRACT

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.


Subject(s)
Animals , Central Nervous System Sensitization , Constriction , Cytochromes , Dehydroepiandrosterone , Dehydroepiandrosterone Sulfate , Hyperalgesia , N-Methylaspartate , Neuralgia , Nitric Oxide Synthase Type II , Nitric Oxide Synthase , Nitric Oxide , Oxidative Stress , Peripheral Nerve Injuries , Phosphorylation , Rats , RNA, Messenger , Rodentia , Sciatic Nerve , Spinal Cord , Spinal Cord Dorsal Horn
2.
Dolor ; 28(69): 22-24, jul. 2018.
Article in Spanish | LILACS | ID: biblio-1117585

ABSTRACT

INTRODUCCIÓN: El dolor lumbar crónico genera alta disfuncionalidad, su tratamiento es complejo y en algunos casos se presenta refractariedad a tratamientos convencionales. El síndrome de sensibilización central por dolor lumbar involucra presencia de síntomas ansiosos, depresivos, trastorno del sueño, fatiga, alteraciones del apetito y disfuncionalidad en actividades de la vida diaria. El manejo del dolor lumbar crónico con síndrome de sensibilización central es dificultoso, requiere de intervenciones multidimensionales y esquemas farmacológicos atípicos. OBJETIVO: Se describe el uso de topiramato como fármaco coadyuvante en el manejo de pacientes con dolor lumbar crónico resistente a tratamiento standard en 25 pacientes. MATERIALES Y MÉTODO: Seguimiento a 12 semanas y evaluación de funcionalidad, sintomatología ansiosa-depresiva, control del dolor y fatiga a través de múltiples escalas. Resultados: La dosis mediana fue de 300mg. El 72 por ciento (18 pacientes) presenta mejoría estadística en síntomas angustiosos, depresivos, sueño, EVA de dolor y fatiga y funcionalidad. Solo el 16 por ciento (4 pac) presentan reacciones adversas que obligan a suspensión del fármaco. El 12 por ciento (3 pacientes) no presentaron respuesta terapéutica. DISCUSIÓN: El topiramato podría ser una opción coadyuvante para el manejo del síndrome de dolor lumbar crónico con síndrome de sensibilización central.


INTRODUCTION: The chronic low back pain causes severe dysfunction, treatment is complex and in some cases it can be refractory to usual treatment. Central Sensitivity syndrome secondary to chronic low back pain is characterized by anxious, depressive, sleep disorders, fatigue, eating disorders and damage in daily activities life. Management of this syndrome must be integrative and multidimensional. OBJECTIVES: Describe the use of topiramate in 25 patients with chronic low back pain for pain relief in refractory patients to standard treatment, during 12 weeks. MATERIALS AND METHODS: Following during 12 weeks, multiples Assessments about anxiety, depression, functionality, sleep quality, VAS pain and fatigue. Results: Median doses 300mg. 72 percent got pain relief, and decrease in anxious depressive symptoms, improve sleep quality, daily function. 16 percent didn't get pain relief and suffered adverse effects forcing suspension of the drug. 12 percent didn't get pain relief without adverse effects. DISCUSSION: Topiramate might be a treatment option for pain relief in these patients.


Subject(s)
Humans , Male , Female , Low Back Pain/psychology , Low Back Pain/drug therapy , Topiramate/therapeutic use , Anticonvulsants/therapeutic use , Anxiety , Pain Measurement , Adjuvants, Pharmaceutic , Follow-Up Studies , Depression , Chronic Pain , Central Nervous System Sensitization/drug effects , Topiramate/administration & dosage , Anticonvulsants/administration & dosage
3.
Med. leg. Costa Rica ; 34(2): 76-81, sep.-dic. 2017. tab
Article in Spanish | LILACS | ID: biblio-894323

ABSTRACT

ResumenEl síndrome de fatiga crónica es una patología que se caracteriza por fatiga intensa de como mínimo seis meses de duración, que se acompaña de otros síntomas y que en ocasiones podría ser tan intenso que causa la disminución de las actividades cotidianas del individuo que lo padece. El comienzo de los síntomas puede ser repentino o también de forma paulatina, muchas veces las personas recuerdan el momento en que comenzó y el principio de estos puede ser un cuadro similar a una gripe. A continuación, se hará una revisión bibliográfica sobre los principales aspectos de esta enfermedad, causa, criterios diagnósticos y tratamiento.


AbstractChronic fatigue syndrome is a pathology characterized by intense fatigue of at least six months duration, which is accompanied by other symptoms and which at times could be so intense that it causes the daily activities of the individual suffering from it to diminish. The onset of symptoms may be sudden or also gradually, many times people remember the time they started and the beginning of these can be a flu-like four. Next, a bibliographic review will be done on the main aspects of this disease, cause, diagnostic criteria and treatment.


Subject(s)
Humans , Physical Examination , Fatigue Syndrome, Chronic/diagnosis , Fatigue , Central Nervous System Sensitization
4.
Article in English | WPRIM | ID: wpr-200207

ABSTRACT

BACKGROUND: Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. METHODS: This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. RESULTS: Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. CONCLUSIONS: Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed.


Subject(s)
Anesthetics, Local , Central Nervous System Sensitization , Herpes Zoster , Humans , Incidence , Injections, Epidural , Nerve Block , Neuralgia, Postherpetic , Stellate Ganglion , Steroids
5.
Article in English | WPRIM | ID: wpr-227123

ABSTRACT

Good pain control after surgery is important to facilitate overall recovery, improve patient satisfaction, decrease morbidity, and reduce health care cost. However, despite heightened awareness and development of new guidelines in recent decades, we have failed to make major improvements in postoperative pain control. Currently available analgesic therapies have limited efficacy, and pain after surgery continues to be a significant clinical problem. Our goal is to develop more effective and safer clinical strategies that will eliminate or greatly reduce postoperative pain, and a better understanding of the mechanisms of pain induced by surgery would be essential to achieve this goal. Evidence suggests that the pathophysiological mechanisms and optimal treatment of postoperative pain are different from many other painful conditions. Recognizing the necessity and importance of relevant pre-clinical models, we have developed and characterized rodent incision models that have close similarities to postoperative pain in patients. Previous studies have demonstrated the clinical relevance and translatability of these pre-clinical models of postoperative pain. In this review, we describe the rodent incision pain models, and summarized our current understanding of the mechanisms of postoperative pain, highlighting key findings from our previous studies using these models.


Subject(s)
Central Nervous System Sensitization , Health Care Costs , Humans , Pain, Postoperative , Patient Satisfaction , Rodentia
6.
Article in Korean | WPRIM | ID: wpr-45957

ABSTRACT

Chronic refractory cough is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main disease that causes chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Treatments include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.


Subject(s)
Central Nervous System Sensitization , Chronic Pain , Cough , Delivery of Health Care , Diagnosis , Dysphonia , Dyspnea , Humans , Hypersensitivity , Neurotransmitter Agents , Pregabalin , Quality of Life , Reflex , Specialization , Speech-Language Pathology , Vocal Cords , Voice Disorders
7.
Article in English | WPRIM | ID: wpr-32718

ABSTRACT

BACKGROUND: A low dose of ketamine can be an effective preemptive analgesic by preventing central sensitization when administered before surgical trauma. In this study, we assessed the preemptive analgesic effect of low-dose ketamine administered intravenously to patients undergoing arthroscopic rotator cuff repair with intra articular ropivacaine injection. METHODS: This randomized, double-blinded study included fifty-six patients scheduled for elective arthroscopic rotator cuff repair. Normal saline (group C) or 0.5 mg/kg of ketamine (group K) was injected intravenously before the skin incision. An intra articular injection using 20 ml of 0.75% ropivacaine was performed in both groups just before wound closure by the surgeon at the end of the surgery. Postoperative pain was assessed by the numeric rating scale (NRS) in the post-anesthesia care unit (PACU) and at 12, 24, and 48 hours postoperatively. The total dose of fentanyl consumption and side effects were recorded. RESULTS: There were no significant differences between the C and K groups for the NRS of pain in the PACU and at 12, 24, and 48 hours after the surgery. In addition, there was also no significant difference in total fentanyl consumption between the two groups. CONCLUSIONS: Preemptive ketamine did not reduce preemptive pain scores and fentanyl consumption in patients who underwent arthroscopic rotator cuff repair with intra articular local anesthetic injection. Therefore, more aggressive and multimodal pain control is required in patients undergoing arthroscopic shoulder surgery regardless of the use of preemptive intravenous ketamine injection.


Subject(s)
Central Nervous System Sensitization , Fentanyl , Humans , Ketamine , Pain, Postoperative , Rotator Cuff , Shoulder , Skin , Wounds and Injuries
8.
Braz. j. phys. ther. (Impr.) ; 19(4): 251-257, July-Aug. 2015. tab, ilus
Article in English | LILACS | ID: lil-761611

ABSTRACT

Introduction: Peripheral and central sensitization are neurophysiological processes that can prolong painful conditions. Painful shoulder conditions are often persistent, perhaps due to the presence of sensitization.Method:This manuscript summarizes six studies that have evaluated those with musculoskeletal shoulder pain for the presence of sensitization.Results:All six manuscripts report evidence of peripheral sensitization, while central sensitization was described in five of the studies. The chronicity of symptoms in subjects who were included in the studies is probably influencing this finding. The primary somatosensory test used to assess sensitization in these studies was Pressure Pain Threshold, a test for lowered nociceptive thresholds.Discussion:It appears that peripheral sensitization manifests consistently in those with musculoskeletal shoulder pathology, probably due to the inflammatory processes related to tissue injury. Central sensitization, while not universally present, was reported in a majority of the manuscripts. Because central sensitization is thought to be a key step on the pathway to chronic pain, evidence for its presence in those with shoulder pain is significant. Clinicians should expect the presence of sensitization with shoulder pathology and make appropriate choices about interventions so as not to exacerbate pain.


Subject(s)
Humans , Pain Threshold/physiology , Shoulder Pain , Musculoskeletal Pain/physiopathology , Central Nervous System Sensitization/physiology
9.
Article in English | WPRIM | ID: wpr-44493

ABSTRACT

BACKGROUND: Opioid induced hyperalgesia (OIH) is related with high opioid dosage, a long duration of opioid administration, and abrupt discontinuation of infused opioids in anesthetic settings. Ketamine is known to attenuate OIH efficiently, but methods of administration and methods to quantify and assess a decrease in OIH vary. We demonstrated the existence of remifentanil-induced hyperalgesia and investigated the ability of ketamine to attenuate OIH. METHODS: Seventy-five patients undergoing laparoscopic gynecologic surgery under remifentanil-based anesthesia were assigned to one of the following groups: (1) group RL (remifentanil 0.05 microg/kg/min), (2) group RH (remifentanil 0.3 microg/kg/min), or (3) group KRH (remifentanil 0.3 microg/kg/min + ketamine 0.5 mg/kg bolus with 5 microg/kg/min infusion intraoperatively). Desflurane was administered for maintenance of anesthesia to target bispectral index scores (40-60) and hemodynamic parameters (heart rate and blood pressure < +/- 20% of baseline values). All parameters related to OIH and its attenuation induced by ketamine were investigated. RESULTS: There was no significant difference among the three groups related to demographic and anesthetic parameters except the end-tidal concentration of desflurane. Additional analgesic consumption, numerical rating scale scores at 6 and 24 h, and cumulative fentanyl dose were significantly higher in group RH than in the other two groups. The value difference of the Touch-Test sensory evaluation was significantly higher negative in group RH than in the other two groups. CONCLUSIONS: Remifentanil-induced hyperalgesia is significantly attenuated by intraoperative bolus and infusion of ketamine. Ketamine also decreased tactile sensitization, as measured by Touch-Test sensory evaluation.


Subject(s)
Analgesics, Opioid , Anesthesia , Blood Pressure , Central Nervous System Sensitization , Female , Fentanyl , Gynecologic Surgical Procedures , Hemodynamics , Humans , Hyperalgesia , Ketamine
10.
Article in Korean | WPRIM | ID: wpr-93653

ABSTRACT

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been a frustrating condition that is characterized by pain in areas including the perineum, rectum, prostate, penis, testicles, and abdomen. Unfortunately, effective treatment for the chronic pelvic pain remains uncertain and most urologists still believe we have little to offer these patients once traditional therapy including antibiotics has failed. Proposed mechanisms in development of pain in CP/CPPS is that biological insult in the context of alterations in psychoimmunoneurendocrine factors produces the chronic pain experience. There is increasing evidence that the chronic pain is associated with long-lasting changes both to the structure and function of the nervous system. Nerve injury, such as in neuropathic pain, peripheral sensitization, and central sensitization might play an important role in CP/CPPS and therefore be a therapeutic target. Newer medications, such as the anticonvulsant gabapentin and pregabalin, are becoming increasingly used for neuropathic pain in CP/CPPS. Now, urologists should understand the neuropathic pain in CP/CPPS and become on some level a pain doctor.


Subject(s)
Abdomen , Anti-Bacterial Agents , Central Nervous System Sensitization , Chronic Pain , Humans , Male , Nervous System , Neuralgia , Pelvic Pain , Penis , Perineum , Prostate , Prostatitis , Rectum , Testis , Pregabalin
11.
Braz. j. med. biol. res ; 47(6): 505-514, 06/2014. tab, graf
Article in English | LILACS | ID: lil-709447

ABSTRACT

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.


Subject(s)
Animals , Female , Central Nervous System Sensitization/drug effects , Cocaine/pharmacology , Estradiol/blood , Motor Activity/drug effects , Progesterone/blood , Stereotyped Behavior/drug effects , Analysis of Variance , Cocaine/administration & dosage , Estradiol/pharmacology , Estrous Cycle/blood , Hormone Replacement Therapy , Ovariectomy , Progesterone/pharmacology , Rats, Wistar , Sex Factors
12.
Article in English | WPRIM | ID: wpr-52957

ABSTRACT

Ketamine has been shown to have analgesic effect by blocking N-methyl-D-aspartate receptor, thus preventing and reducing central sensitization caused by peripheral nociceptive stimulation. However, due to lack of knowledge about its safety and toxicity in the central nervous system, either epidural or intrathecal injection of ketamine still remains controversial. Here, we describe a case report of satisfactory pain relief after the addition of ketamine in epidural injection in a patient with severe herpes zoster pain that was refractory to conventional medication, intravenous opioids and continuous epidural block. This case indicates the viability of epidural ketamine injection in patients with intractable herpetic neuralgia.


Subject(s)
Analgesia, Epidural , Analgesics, Opioid , Central Nervous System , Central Nervous System Sensitization , Herpes Zoster , Humans , Injections, Epidural , Injections, Spinal , Ketamine , N-Methylaspartate , Neuralgia
13.
Hanyang Medical Reviews ; : 81-86, 2014.
Article in Korean | WPRIM | ID: wpr-31109

ABSTRACT

Pain is the most common symptom of almost all rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, osteoarthritis, fibromyalgia, and others. In addition to commonly known peripheral or nociceptive pain mechanisms, central sensitization plays an essential and significant role as a cause of chronic pain in rheumatic diseases. Chronic pain is also associated with several psychiatric diseases such as depression and anxiety disorders and other various central pain maladies such as irritable bowel syndrome and temporomandibular joint disorder. Therefore, many researchers and clinicians have inferred that similar therapeutic strategies may be employed against this spectrum of disorders. Utilizing recently gained understanding of chronic pain mechanisms will allow a targeted therapeutic approach to individuals who have rheumatologic disease with different spectrum of symptomatic severity and disability.


Subject(s)
Anxiety Disorders , Arthritis, Rheumatoid , Central Nervous System Sensitization , Chronic Pain , Depression , Fibromyalgia , Irritable Bowel Syndrome , Lupus Erythematosus, Systemic , Mental Disorders , Nociceptive Pain , Osteoarthritis , Rheumatic Diseases , Spondylitis, Ankylosing , Temporomandibular Joint Disorders
14.
Article in English | WPRIM | ID: wpr-187154

ABSTRACT

It has been reported that long-term enhancement of superficial dorsal horn (DHs) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. We tested whether impaired clearance of K+ and glutamate by glia in DHs may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted decrease of the DHs optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted increase in the postsynaptic response of the DHs like LTP. It also is shown that LTP(FC) does not occur in the presence of APV, and becomes progressively smaller as [K+]o in the perfusion solution decreased from 3.0 mM to 0.0 mM. Interestingly LTP(FC) is reduced by bath application of Bic. Whole-cell patch recordings were carried out to evaluate the effects of FC on the response of DHs neurons to puffer-applied GABA. The observations reveal that transient exposure to FC is reliably accompanied by a prolonged (>1 hr) depolarizing shift of the equilibrium potential for the DHs neuron transmembrane ionic currents evoked by GABA. Considered collectively, the findings demonstrate that LTP(FC) involves (1) elevation of [K+]o in the DHs, (2) NMDAR activation, and (3) conversion of the effect of GABA on DHs neurons from inhibition to excitation. It is proposed that a transient impairment of astrocyte energy production can trigger the cascade of dorsal horn mechanisms that underlies hyperalgesia and persistent pain.


Subject(s)
Animals , Astrocytes , Baths , Central Nervous System Sensitization , Electric Stimulation , gamma-Aminobutyric Acid , Glutamic Acid , Horns , Hyperalgesia , Neuroglia , Neurons , Perfusion , Posterior Horn Cells , Rats , Spinal Cord , Spinal Nerve Roots , Synaptic Transmission
15.
Article in Korean | WPRIM | ID: wpr-102158

ABSTRACT

Recent studies indicate that reactive oxygen species (ROS) can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In this study, we investigated the effects of NaOCl, a ROS donor, on neuronal excitability and the intracellular calcium concentration ([Ca2+]i) in spinal substantia gelatinosa (SG) neurons. In current clamp conditions, the application of NaOCl caused a membrane depolarization, which was inhibited by pretreatment with phenyl-N-tert-buthylnitrone (PBN), a ROS scavenger. The NaOCl-induced depolarization was not blocked however by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Confocal scanning laser microscopy was used to confirm whether NaOCl increases the intracellular ROS level. ROS-induced fluorescence intensity was found to be increased during perfusion of NaOCl after the loading of 2',7'-dichlorofluorescin diacetate (H2DCF-DA). NaOCl-induced depolarization was not blocked by pretreatment with external Ca2+ free solution or by the addition of nifedifine. However, when slices were pretreated with the Ca2+ ATPase inhibitor thapsigargin, NaOCl failed to induce membrane depolarization. In a calcium imaging technique using the Ca2+-sensitive fluorescence dye fura-2, the [Ca2+]i was found to be increased by NaOCl. These results indicate that NaOCl activates the excitability of SG neurons via the modulation of the intracellular calcium concentration, and suggest that ROS induces nociception through a central sensitization.


Subject(s)
Animals , Calcium , Calcium-Transporting ATPases , Central Nervous System Sensitization , Dithiothreitol , Fluoresceins , Fluorescence , Fura-2 , Humans , Membranes , Microscopy, Confocal , Neurons , Nociception , Perfusion , Rats , Reactive Oxygen Species , Substantia Gelatinosa , Thapsigargin , Tissue Donors
16.
Article in English | WPRIM | ID: wpr-74419

ABSTRACT

BACKGROUND: Recent research has shown that reactive oxygen species (ROS) play a significant role in the development and persistence of neuropathic pain through central sensitization via N-methyl-D-aspartate (NMDA) receptor activation. In the present study, we examined whether the intraperitoneal administration of vitamins C and E alone or together could alleviate mechanical allodynia in a chronic post-ischemia pain (CPIP) rat model. METHODS: Vitamins C and E were administered intraperitoneally to 48 male Sprague Dawley rats once per day for 3 days before hindpaw ischemia-reperfusion (I/R) injury was induced. On the third day, the CPIP rat model was produced by inducing ischemia in the left hindpaw by applying an O-ring for 3 h, followed by reperfusion. Three days after reperfusion, hindpaw mechanical allodynia was assessed by measuring the withdrawal response to von Frey filament stimulation. The rats were sacrificed immediately after behavioral testing to determine the phosphorylated NMDA receptor subunit 1 (pNR1) and extracellular-signal-regulated kinases (pERK) levels in the spinal cord. RESULTS: When the antioxidant vitamins C and E were administered intraperitoneally to CPIP rats, I/R injury-induced mechanical allodynia was attenuated, and pNR1 and pERK levels were decreased in the rat spinal cord. Additionally, the co-administration of both vitamins had an increased antiallodynic effect. CONCLUSIONS: The reduced phosphorylated NR1 and ERK levels indicate that vitamins C and E inhibit the modulation of spinal cord neuropathic pain processing. Co-administration of vitamins C and E had a greater antiallodynic effect.


Subject(s)
Animals , Antioxidants , Ascorbic Acid , Central Nervous System Sensitization , Complex Regional Pain Syndromes , Humans , Hyperalgesia , Inositol Phosphates , Ischemia , Male , Mitogen-Activated Protein Kinases , Models, Animal , N-Methylaspartate , Neuralgia , Phosphotransferases , Prostaglandins E , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species , Receptors, N-Methyl-D-Aspartate , Reperfusion , Reperfusion Injury , Spinal Cord , Vitamin E , Vitamins
17.
Article in English | WPRIM | ID: wpr-23373

ABSTRACT

Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future.


Subject(s)
Central Nervous System Sensitization , Chronic Pain , Comorbidity , Cystitis, Interstitial , Depression , Fatigue Syndrome, Chronic , Female , Gonadal Hormones , Heredity , Humans , Hyperalgesia , Hypersensitivity , Irritable Bowel Syndrome , Migraine Disorders , Odds Ratio , Parasympatholytics , Polymorphism, Genetic , Prevalence , Prognosis , Quality of Life , Sleep Initiation and Maintenance Disorders , Stroke , Suicide
18.
Article in English | WPRIM | ID: wpr-130225

ABSTRACT

BACKGROUND: Reactive oxygen species (ROS) such as superoxide radicals, hydrogen peroxide, nitric oxide, and nitroperoxide, cause oxidative stress which interferes with normal cell functioning, resulting in cell damage. It is reported to be associated with chronic pain, especially neuropathic pain, and inflammatory pain. ROS is also closely related to central sensitization. Therefore, this study was designed to explore the effects of Phenyl N-tert-butylnitrone (PBN), an ROS scavenger, in acute, continuous, and increasing pain caused by central sensitization. METHODS: Male Sprague-Dawley rats were divided into 2 groups, an intraperitoneal group (IP) and an intrathecal group (IT), and once again divided into an experimental group and a control group. The experimental group was injected with Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, either intraperitoneally or intrathecally. After inducing pain by injecting formalin into the hind paw, pain behaviors were measured. Lumbar enlargement immmunohistochemistry was performed to assess nitrotyrosine, an oxidative stress marker, to identify the degree of protein nitration. RESULTS: Both experimental groups of IP and IT showed statistically significant decreases in the number of flinches compared to the control group in phase 1 and 2. Immunohistochemical evaluation in the control group revealed an increase in nitrated proteins in the gray matter of the lumbar spinal cord, but a significant decrease in nitrated proteins in the gray matter of lumbar spinal cord of the experimental group. CONCLUSIONS: Intraperitoneal and intrathecal administration of PBN decreases analgesic behaviors, allowing us to believe that ROS is mainly responsible for acute pain and central sensitization.


Subject(s)
Acute Pain , Animals , Central Nervous System Sensitization , Chronic Pain , Formaldehyde , Humans , Hydrogen Peroxide , Male , Neuralgia , Nitric Oxide , Oxidative Stress , Pain Measurement , Proteins , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species , Spinal Cord , Superoxides , Tyrosine
19.
Article in English | WPRIM | ID: wpr-130212

ABSTRACT

BACKGROUND: Reactive oxygen species (ROS) such as superoxide radicals, hydrogen peroxide, nitric oxide, and nitroperoxide, cause oxidative stress which interferes with normal cell functioning, resulting in cell damage. It is reported to be associated with chronic pain, especially neuropathic pain, and inflammatory pain. ROS is also closely related to central sensitization. Therefore, this study was designed to explore the effects of Phenyl N-tert-butylnitrone (PBN), an ROS scavenger, in acute, continuous, and increasing pain caused by central sensitization. METHODS: Male Sprague-Dawley rats were divided into 2 groups, an intraperitoneal group (IP) and an intrathecal group (IT), and once again divided into an experimental group and a control group. The experimental group was injected with Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, either intraperitoneally or intrathecally. After inducing pain by injecting formalin into the hind paw, pain behaviors were measured. Lumbar enlargement immmunohistochemistry was performed to assess nitrotyrosine, an oxidative stress marker, to identify the degree of protein nitration. RESULTS: Both experimental groups of IP and IT showed statistically significant decreases in the number of flinches compared to the control group in phase 1 and 2. Immunohistochemical evaluation in the control group revealed an increase in nitrated proteins in the gray matter of the lumbar spinal cord, but a significant decrease in nitrated proteins in the gray matter of lumbar spinal cord of the experimental group. CONCLUSIONS: Intraperitoneal and intrathecal administration of PBN decreases analgesic behaviors, allowing us to believe that ROS is mainly responsible for acute pain and central sensitization.


Subject(s)
Acute Pain , Animals , Central Nervous System Sensitization , Chronic Pain , Formaldehyde , Humans , Hydrogen Peroxide , Male , Neuralgia , Nitric Oxide , Oxidative Stress , Pain Measurement , Proteins , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species , Spinal Cord , Superoxides , Tyrosine
20.
Article in English | WPRIM | ID: wpr-156171

ABSTRACT

BACKGROUND: Reactive oxygen species and inflammatory responses contribute to the development of neuropathic pain. Superoxide serves to mediate cell signaling processes and tissue injury during inflammation. We examined the effects of superoxide on the development and maintenance of mechanical allodynia, as well as its contribution to central sensitization in a superoxide-rich animal model of neuropathic pain. METHODS: Chronic post-ischemia pain (CPIP) was induced via the left hindpaw ischemia for 3 h, followed by reperfusion. Superoxide dismutase (4,000 U/kg, i.p.) was administered either 5 min before ischemia (BI), 5 min before reperfusion (BR), or 3 days after reperfusion (3AR). Withdrawal thresholds of the four paws were measured to assess the mechanical allodynia and the effects of circulating xanthine oxidase (XO)-mediated superoxide production. In addition, we measured the levels of N-methyl D-aspartate receptor subunit 1 phosphorylation (p-NR1) in the ipsilateral and contralateral spinal cord (L4-6), by Western blotting, to examine the superoxide-mediated central sensitization. Superoxide production was assessed by allopurinol-sensitive, XO-mediated lipid peroxidation of the spinal cord and gastrocnemius muscles. RESULTS: Withdrawal thresholds of forepaws did not vary across the 7 days of testing. In the hindpaws, both ipsilateral and contralateral mechanical allodynia was most attenuated in the BR group, followed by the BI and 3AR groups. The degree of NR1 activation was in contrast to the changes in the withdrawal thresholds. CONCLUSIONS: These data suggest that superoxide is involved in the development and maintenance of mechanical allodynia, particularly via central sensitization in the spinal cord.


Subject(s)
Animals , Blotting, Western , Central Nervous System Sensitization , D-Aspartic Acid , Hyperalgesia , Inflammation , Ischemia , Lipid Peroxidation , Models, Animal , Neuralgia , Phosphorylation , Rats , Reactive Oxygen Species , Reperfusion , Spinal Cord , Superoxide Dismutase , Superoxides , Xanthine Oxidase
SELECTION OF CITATIONS
SEARCH DETAIL