Validation of the Brazilian version of the child pain catastrophizing scale and its relationship with a marker of central sensitization

Abstract Objectives The Pain Catastrophizing Scale-Child version (PCS-C) allows to identify children who are prone to catastrophic thinking. We aimed to adapt the Brazilian version of PCS-C (BPCS-C) to examine scale psychometric properties and factorial structure in children with and without chronic pain. Also, we assessed its correlation with salivary levels of Brain-Derived Neurotrophic factor (BDNF). Methods The Brazilian version of PCS-C was modified to adjust it for 7-12 years old children. To assess psychometric properties, 100 children (44 with chronic pain from a tertiary hospital and 56 healthy children from a public school) answered the BPCS-C, the visual analogue pain scale, and questions about pain interference in daily activities. We also collected a salivary sample to measure BDNF. Results We observed good internal consistency (Cronbach's value = 0.81). Parallel analysis retained 2 factors. Confirmatory factor analysis of our 2-factor model revealed consistent goodness-of-fit (IFI = 0.946) when compared to other models. There was no correlation between visual analogue pain scale and the total BPCS-C score; however, there was an association between pain catastrophizing and difficulty in doing physical activities in school (p= 0.01). BPCS-C total scores were not different between groups. We found a marginal association with BPCS-C (r= 0.27, p= 0.01) and salivary BDNF levels. Discussion BPCS-C is a valid instrument with consistent psychometric properties. The revised 2-dimension proposed can be used for this population. Children catastrophism is well correlated with physical limitation, but the absence of BPCS-C score differences between groups highlights the necessity of a better understanding about catastrophic thinking in children.

Profil épidémio-clinique, fonctionnel et de sensibilisation aux allergènes chez les asthmatiques suivis en consultation en milieu Africain à Libreville, Gabon / Epidemiological-clinical, functional profile and sensitization to allergens in asthmatics followed in consultation in an African environment in Libreville, Gabon

Introduction : La prévalence de l'asthme au niveau national est inconnue. L'objectif était de déterminer la prévalence hospitalière de l'asthme et la sensibilisation aux pneumallergènes standards.Patients et Méthodes : Il s'agit d'une étude transversale, rétrospective qui a consisté en l'analyse descriptive de 164 dossiers de patients asthmatiques reçus pour consultation au CHU de Libreville sur une période d'activité de 36 mois. La mesure du VEMS pré et post-bronchodilatateur ainsi que les prick-tests ont été réalisés. Les extraits standardisés suivants étaient testés : Dermatophagoïdes pteronyssinus et farinae, les phanères (chien et chat), les plantes vertes (Cynodon dactylon) et les moisissures (Alternaria sp). Résultats : Des 2798 patients reçus en consultation de pneumologie, 164 l'étaient pour un asthme soit une fréquence 5,8%. Parmi les 164 patients asthmatiques 59,8%(n=98) étaient des femmes avec un sex-ratio à 0,67. La moyenne d'âge de la population d'étude était de 31±18,1 ans, des extrêmes de 5 et 81 ans. Plus de la moitié des patients résidait en milieu urbain (59,7%), et était sans revenu (50,7%). L'asthme était associé à la rhinite allergique dans 72,6%. Seuls 45 patients avaient réalisé les prick tests parmi lesquels la sensibilisation aux acariens (n=37/45 ; 82,2%) était fréquente et dominée par Dermatophagoïdes pteronyssinus (n=32/37 ; 86,5%). La sensibilisation à Blomia tropicalis était de 73,0% (n=27/37). La sensibilisation aux phanères d'animaux (chiens et chats) était observée chez 9 patients (n=9/45 ; 20,0%). Aucune sensibilisation à l'Alténaria sp n'a été relevée. Le déficit ventilatoire obstructif proximal et distal a été observé dans 45,8% des cas (n=60/131).Conclusion : La prévalence de l'asthme est relativement élevé dans notre contexte d'exercice. Le taux sensibilisation révélé est le témoin d'une forte pression allergénique exercée par l'environnement domestique

Introduction: The national prevalence of asthma is unknown. The objective was to determine the hospital prevalence of asthma and sensitization to standard airborne allergens. Patients and Methods: This is a cross-sectional, retrospective study which consisted of the descriptive analysis of 164 records of asthmatic patients received for consultation at the University Hospital of Libreville over a period of activity of 36 months. Measurement of pre- and post-bronchodilator FEV1 as well as prick-tests were performed. The following standardized extracts were tested: Dermatophagoides pteronyssinus and farinae, skin appendages (dog and cat), green plants (Cynodon dactylon) and molds (Alternaria sp).Results: Of the 2798 patients seen in a pulmonology consultation, 164 were for asthma, i.e. a frequency of 5.8%. Among the 164 asthmatic patients 59.8% (n=98) were women with a sex ratio of 0.67. The average age of the study population was 31 ± 18.1 years, extremes of 5 and 81 years. More than half of the patients lived in urban areas (59.7%), and had no income (50.7%). Asthma was associated with allergic rhinitis in 72.6%. Only 45 patients had performed prick tests,among which sensitization to house dust mites (n=37/45; 82.2%) was frequent and dominated by Dermatophagoides pteronyssinus (n=32/37; 86.5%). Sensitization to Blomia tropicalis was 73.0% (n=27/37). Sensitization to animal dander (dogs and cats) was observed in 9 patients (n=9/45; 20.0%). No sensitization to Altenaria sp was noted. Proximal and distal obstructive ventilatory deficit was observed in 46.5% of cases (n=60/130).Conclusion: The prevalence of asthma is relatively high in our exercise context. The sensitization rate revealed is the witness of a strong allergenic pressure exerted by the domestic environment.

Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats / 中国中药杂志

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

Expression of glycine receptor α3 subunit in neuropathic and inflammatory central pain sensitization

INTRODUCTION: Increasing evidence suggests that changes in the balance of excitatory/inhibitory neurotransmission are involved in the development of the majority of chronic pain forms. In this context, impairment in glycine mediated inhibitory neurotransmission is thought to play a critical role in the disinhibition that accounts for the development and maintenance of central pain hypersensitivity. AIMS: The goal of this study was to evaluate the Glycine Receptor α3 subunit (α3GlyR) expression in neuropathic (Chronic Constriction Injury, CCI) and inflammatory (Zymosan A injected) animal models of chronic pain. RESULTS AND CONCLUSION: RT-qPCR analysis of spinal cord samples showed that glra3 gene expression does not change after 3 days of CCI and 4 hours of Zymosan A injection. However, we found that protein levels evaluated by Western blot increased after inflammatory pain. These data suggest that central sensitization is differentially regulated depending on the type of pain. α3GlyR protein expression plays an important role in the first step of inflammatory pain establishment.

Spinal Nitric Oxide Synthase Type II Increases Neurosteroid-metabolizing Cytochrome P450c17 Expression in a Rodent Model of Neuropathic Pain

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.

Uso del topiramato en pacientes con síndrome de dolor lumbar crónico con síntomas ansiosos y depresivos secundarios a sensibilización central con y sin compromiso neuropático resistente a tratamiento convencional / Use of topiramato in patients with chronic lumbar pain syndrome with ansiosius symptoms and secondary depression to central sensitization with and without neuro-pathic commitment resistant to conventional treatment

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.

Síndrome de fatiga / Fatigue syndrome

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.

Effects of applying nerve blocks to prevent postherpetic neuralgia in patients with acute herpes zoster: a systematic review and meta-analysis

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.

Mechanisms of postoperative pain

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.

Chronic Refractory Cough / 대한내과학회지

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.

The effect of preemptive intravenous ketamine on postoperative pain in patients undergoing arthroscopic rotator cuff repair with intra articular ropivacaine injection

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.

The role of sensitization in musculoskeletal shoulder pain

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.

Effect of intraoperative infusion of ketamine on remifentanil-induced hyperalgesia / 대한마취과학회지

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.

Neuropathic Pain in Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)

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.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

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.

The effect of ketamine as an additive in epidural block on the intractable herpetic neuralgia: a case report / 대한마취과학회지

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.

The Role of Central Sensitization in Chronic Pain of Rheumatic Diseases / 한양의대학술지

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.

Attenuated Glial K+ Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord

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.

Effects of NaOCl on Neuronal Excitability and Intracellular Calcium Concentration in Rat Spinal Substantia Gelatinosa Neurons

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.

Irritable Bowel Syndrome and Migraine: Bystanders or Partners?

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.