Effects of Lidocaine Infusion during Experimental Endotoxemia in Horses

Background The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Hypothesis Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Animals Twelve horses. Methods Two equal groups (n = 6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by a 6-hour continuous rate infusion of GI or GII (0.05 mg/kg BW/min). Treatment efficacy was judged from change in arterial blood pressure, peripheral blood and peritoneal fluid (PF) variables (total and differential cell counts, enzyme activities, and cytokine concentrations), and clinical scores (CS) for behavioral evidence of abdominal pain or discomfort during the study. Results Compared with the control group, horses treated with lidocaine had significantly lower CS and serum and PF tumor necrosis factor-alpha (TNF-alpha) activity. At several time points in both groups, total and differential cell counts, glucose, total protein and fibrinogen concentrations, and alkaline phosphatase, creatine kinase, and TNF-alpha activities were significantly different from baseline values both in peripheral blood and in PF. Conclusions and Clinical Importance Lidocaine significantly decreased severity of CS and inhibited TNF-alpha activity in PF.

Acute and persistent nociceptive paw sensitisation in mice: The involvement of distinct signalling pathways

Aims: Many fundamental pharmacological studies in pain and inflammation have been performed on rats. However, the pharmacological findings were generally not extended to other species in order to increase their predictive therapeutic value. We studied acute and chronic inflammatory nociceptive sensitisation of mouse hind paws by prostaglandin E(2) (PGE(2)) or dopamine (DA), as previously described in rats. We also investigated the participation of the signalling pathways in acute and persistent sensitisation. Main methods: Mechanical sensitisation (hypernociception) induced by intraplantar administrations of PGE(2) or DA was evaluated with an electronic pressure meter. The signalling pathways were pharmacologically investigated with the pre-administration of adenylyl cyclase (AC), cAMP-dependent protein kinase (PKA), protein kinase C epsilon (PKC epsilon), and the extracellular signal-related kinase (ERK) inhibitors. Key findings: Single or 14 days of successive intraplantar injections of PGE(2) or DA-induced acute and persistent hypernociception (lasting for more than 30 days), respectively. The involvement of AC, PKA or PKC epsilon was observed in the acute hypernociception induced by PGE(2), while PKA or PKC epsilon were continuously activated during the period of persistent hypernociception. The acute hypernociception induced by DA involves activation of ERK, PKC epsilon, AC or PKA, while persistent hypernociception implicated ERK activation, but not PKA, PKC epsilon or AC. Significance: In mice, acute and persistent paw sensitisation involves the different activation of kinases, as previously described for rats. This study opens the possibility of comparing pharmacological approaches in both species to further understand acute and chronic inflammatory sensitisation, and possibly associated genetic manipulations. (C) 2009 Elsevier Inc. All rights reserved.

Quercetin Reduces Inflammatory Pain: Inhibition of Oxidative Stress and Cytokine Production

Quercetin (1) is known to have both antioxidant and antinociceptive effects. However, the mechanism involved in its antinociceptive effect is not fully elucidated. Cytokines and reactive oxygen species have been implicated in the cascade of events resulting in inflammatory pain. Therefore, we evaluated the antinociceptive mechanism of 1 focusing on the role of cytokines and Oxidative stress. Intraperitoneal and oral treatments with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid and phenyl-p-benzoquinone and also the second phase of formalin- and carrageenin-induced mechanical hypernociception. Compound I also inhibited the hypernociception induced by cytokines (e.g., TNF alpha and CXCL1), but not by inflammatory mediators that directly sensitize the nociceptor such as PGE(2) and dopamine. On the other hand, 1 reduced carrageenin-induced IL-1 beta production as well as carrageenin-induced decrease of reduced glutathione (GSH) levels. These results suggest that I exerts its analgesic effect by inhibiting pro-nociceptive cytokine production and the oxidative imbalance mediation of inflammatory pain.

Antinociceptive activity and toxicology of the lectin from Canavalia boliviana seeds in mice

The aim of the present study was to evaluate the potential antinociceptive and toxicity of Canavalia boliviana lectin (CboL) using different methods in mice. The role of carbohydrate-binding sites was also investigated. CboL given to mice daily for 14 days at doses of 5 mg/kg did not cause any observable toxicity. CboL (1, 5, and 10 mg/kg) administered to mice intravenously inhibited abdominal constrictions induced by acetic acid and the two phases of the formalin test. In the hot plate and tail immersion tests, the same treatment of CboL induced significant increase in the latency period. In the hot plate test, the effect of CboL (5 mg/kg) was reversed by naloxone (1 mg/kg), indicating the involvement of the opioid system. In the open-field and rota-rod tests, the CboL treatment did not alter animals` motor function. These results show that CboL presents antinociceptive effects of both central and peripheral origin, involving the participation of the opioid system via lectin domain.

Fos expression in the NTS in response to peripheral chemoreflex activation in awake rats

Chemoreflex afferent fibers terminate in the nucleus tractus solitarii (NTS), but the specific location of the NTS neurons excited by peripheral chemoreflex activation remains to be characterized. Here, the topographic distribution of chemoreflex sensitive cells at the commissural NTS was evaluated. To reach this goal, Fos-immunoreactive neurons (Fos-ir) were accounted in rostro-caudal levels of the intermediate and caudal commissural NTS, after intermittent chemoreflex activation with intravenous injection of potassium cyanide [KCN (80 mu g/kg) or saline (0.9%, vehicle), one injection every 3 min during 30 min]. In response to intermittent intravenous injections of KCN, a significant increase in the number of Fos-ir neurons was observed specifically in the lateral intermediate commissural NTS [(LI)NTS (82 +/- 9 vs. 174 +/- 16, cell number mean per section)] and lateral caudal commissural NTS [(LI)NTS (71 +/- 9 vs. 199 +/- 18, cell number mean per section)]. To evaluate the influence of baroreceptor-mediated inputs following the increase in blood pressure during intermittent chemoreflex activation, we performed an intermittent activation of the arterial baroreflex by intravenous injection of phenylephrine [1.5 mu g/kg iv (one injection every 3 min during 30 min)]. This procedure induced no change in Fos-ir in (LI)NTS (64 +/- 6 vs. 62 +/- 12, cell number mean per section) or (LC)NTS (56 +/- 15 vs. 77 +/- 12, cell number mean per section). These data support the involvement of the commissural NTS in the processing of peripheral chemoreflex, and provide a detailed characterization of the topographical distribution of activated neurons within this brain region. (C) 2009 Elsevier B.V. All rights reserved.

Are l-glutamate and ATP cotransmitters of the peripheral chemoreflex in the rat nucleus tractus solitarius ?

Peripheral chemoreflex activation in awake rats or in the working heart-brainstem preparation (WHBP) produces sympathoexcitation, bradycardia and an increase in the frequency of phrenic nerve activity. Our focus is the neurotransmission of the sympathoexcitatory component of the chemoreflex within the nucleus of the tractus solitarius (NTS), and recently we verified that the simultaneous antagonism of ionotropic glutamate and purinergic P(2) receptors in the NTS blocked the pressor response and increased thoracic sympathetic activity in awake rats and WHBP, respectively, in response to peripheral chemoreflex activation. These previous data suggested the involvement of ATP and L-glutamate in the NTS in the processing of the sympathoexcitatory component of the chemoreflex by unknown mechanisms. For a better understanding of these mechanisms, here we used a patch-clamp approach in brainstem slices to evaluate the characteristics of the synaptic transmission of NTS neurons sending projections to the ventral medulla, which include the premotor neurons involved in the generation of the sympathetic outflow. The NTS neurons sending projections to the ventral medulla were identified by previous microinjection of the membrane tracer dye, 1,1`-dioctadecyl-3,3,3`,3`-tetramethylindocarbocyanine perchlorate (DiI), in the ventral medulla and the spontaneous (sEPSCs) and tractus solitarius (TS)-evoked excitatory postsynaptic current (TS-eEPSCs) were recorded using patch clamp. With this approach, we made the following observations on NTS neurons projecting to the ventral medulla: (i) the sEPSCs and TS-eEPSCs of DiI-labelled NTS neurons were completely abolished by 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX), an antagonist of ionotropic non-NMDA glutamatergic receptors, showing that they are mediated by L-glutamate; (ii) application of ATP increased the frequency of appearance of spontaneous glutamatergic currents, reflecting an increased exocytosis of glutamatergic vesicles; and (iii) ATP decreased the peak of TS-evoked glutamatergic currents. We conclude that L-glutamate is the main neurotransmitter of spontaneous and TS-evoked synaptic activities in the NTS neurons projecting to the ventral medulla and that ATP has a dual modulatory role on this excitatory transmission, facilitating the spontaneous glutamatergic transmission and inhibiting the TS-evoked glutamatergic transmission. These data also suggest that ATP is not acting as a cotransmitter with L-glutamate, at least at the level of this subpopulation of NTS neurons studied.

INTERMITTENT ACTIVATION OF PERIPHERAL CHEMORECEPTORS IN AWAKE RATS INDUCES Fos EXPRESSION IN ROSTRAL VENTROLATERAL MEDULLA-PROJECTING NEURONS IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS

Despite the well-established sympathoexcitation evoked by chemoreflex activation, the specific sub-regions of the CNS underlying such sympathetic responses remain to be fully characterized. In the present study we examined the effects of intermittent chemoreflex activation in awake rats on Fos-immunoreactivity (Fos-ir) in various subnuclei of the paraventricular nucleus of the hypothalamus (PVN), as well as in identified neurosecretory preautonomic PVN neurons. In response to intermittent chemoreflex activation, a significant increase in the number of Fos-ir cells was found in autonomic-related PVN subnuclei, including the posterior parvocellular, ventromedial parvocellular and dorsal-cap, but not in the neurosecretory magnocellular-containing lateral magnocellular subnucleus. No changes in Fos-ir following chemoreflex activation were observed in the anterior PVN subnucleus. Experiments combining Fos immunohistochemistry and neuronal tract tracing techniques showed a significant increase in Fos-ir in rostral ventrolateral medulla (RVLM)-projecting (PVN-RVLM), but not in nucleus of solitarii tract (NTS)-projecting PVN neurons. In summary, our results support the involvement of the PVN in the central neuronal circuitry activated in response to chemoreflex activation, and indicate that PVN-RVLM neurons constitute a neuronal substrate contributing to the sympathoexcitatory component of the chemoreflex. Published by Elsevier Ltd on behalf of IBRO.

Role of cholinergic, opioidergic and GABAergic neurotransmission of the dorsal hippocampus in the modulation of nociception in guinea pigs

Aims: Several physiological, pharmacological and behavioral lines of evidence suggest that the hippocampal formation is involved in nociception. The hippocampus is also believed to play an important role in the affective and motivational components of pain perception. Thus, Our aim was to investigate the participation of cholinergic, opioidergic and GABAergic systems of the dorsal hippocampus (DH) in the modulation of nociception in guinea pigs. Main methods: The test used consisted of the application of a peripheral noxious stimulus (electric shock) that provokes the emission of a vocalization response by the animal. Key findings: Our results showed that, in guinea pigs, microinjection of carbachol, morphine and bicuculline into the DH Promoted anti nociception, while muscimol promoted pronociception. These results were verified by a decrease and all increase, respectively, in the vocalization index in the vocalization test. This antinociceptive effect of carbachol (2.7 nmol) was blocked by previous administration of atropine (0.7 nmol) or naloxone (1.3 nmol) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol) into the DH was prevented by pretreatment with naloxone (1.3 nmol) or muscimol (0.5 nmol). At doses of 1.0 nmol, muscimol microinjection caused pronociception, while bicuculline promoted antinociception. Significance: These results indicate the involvement of the cholinergic, opioidergic and GABAergic systems of the DH in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalin from interneurons of the DH, Which Would inhibit GABAergic neurons, resulting in antinociception. (C) 2008 Elsevier Inc. All rights reserved.

Thiele massage as a therapeutic option for women with chronic pelvic pain caused by tenderness of pelvic floor muscles

Aims and objectives Musculoskeletal system has been found to be involved in genesis and perpetuation of chronic pelvic pain (CPP) and has strong evidences that up to 80% of women with CPP present dysfunction of the musculoskeletal system. In this study, we report a series of women with CPP caused by tenderness of pelvic floor muscles successfully treated with Thiele massage. Methods Were included in this study six women with CPP caused by tenderness of the levator ani muscle that underwent transvaginal massage using the Thiele technique, over a period of 5 minutes repeated once a week for 4 weeks. After 1 month, the women returned for follow-up. Results The median tenderness score for the six women evaluated was 3 at the first evaluation and 0 after 1 month of follow-up (P < 0.01). The mean Visual Analogue Scale and McGill Pain Index scores were 8.1 and 34, respectively, at the first evaluation, and 1.5 and 16.6 at follow-up (P < 0.01). Conclusion Thiele massage appears to be very helpful for women with CPP caused by tenderness of the levator ani muscle. However, these results are preliminary and a larger number of women are necessary to obtain more conclusive results.

Importance of Pelvic Muscle Tenderness Evaluation in Women with Chronic Pelvic Pain

Objective. To determine the prevalence of pelvic muscle tenderness in women with chronic pelvic pain (CPP) and to assess the importance of evaluating muscle tenderness in such women. Design. Observational study of 48 healthy female volunteers and 108 women with CPP, who were clinically evaluated for pelvic muscle tenderness by two researchers blinded to all clinical data. Results. The frequency of clinically detected pelvic muscle tenderness was significantly higher in women with CPP than in healthy volunteers (58.3% vs 4.2%, P < 0.001). Among women with CPP, those with pelvic muscle tenderness had higher Beck Depression Index scores (22 [6-42] vs 13 [3-39], P = 0.02) and higher rates of dyspareunia (63.5% [40/63] vs 28.9% [13/45], P < 0.004) and constipation (46.0% [29/63] vs 26.7% [12/45], P = 0.05) than those without pelvic muscle tenderness. Conclusion. Tenderness of pelvic muscles was highly prevalent among women with CPP and was associated with higher BDI scores and higher rates of dyspareunia and constipation. Determination of pelvic muscle tenderness may help in identifying women who require more intense treatment for CPP.

High levels of anxiety and depression have a negative effect on quality of life of women with chronic pelvic pain

Chronic pelvic pain (CPP) is a common and complex disease whose cause is often clinically inexplicable, with consequent difficulty in diagnosis and treatment. Patients with CPP have high levels of anxiety and depression, with a consequent impairment of their quality of life. The objective of this study was to determine the prevalence of anxiety and depression and their impact on the quality of life of women with CPP. A cross-sectional controlled study was conducted on 52 patients with CPP and 54 women without pain. Depression and anxiety were evaluated by the Hospital Anxiety and Depression Scale, and quality of life was evaluated by the World Health Organization Quality of life Whoqol-bref questionnaire. Data were analysed statistically by the Mann-Whitney U-test, the Fisher exact test, chi-square test and Spearman correlation test. The prevalence of anxiety was 73% and 37% in the CPP and control groups, respectively, and the prevalence of depression was 40% and 30% respectively. Significant differences between groups were observed in the physical, psychological and social domains. Patients with higher anxiety and depression scores present lower quality of life scores. The fact that DPC is a syndromic complex, many patients enter a chronic cycle of search for improvement of medical symptoms. The constant presence of pain may be responsible for affective changes in dynamics, family, social and sexual. Initially the person is facing the loss of a healthy body and active, to a state of dependence and limitations. In this study, patients with higher scores of anxiety and depression scores had lower quality of life and patients with lower scores of anxiety and depression had scores of quality of life. These results show that perhaps the depression and anxiety may be related to the negative impact on quality of life of these patients. In view of this association, we emphasise the importance of a specific approach to the treatment of anxiety and depression together with clinical treatment to improve the quality of life of these patients.

Primary adenocarcinoma of the fallopian tube as an incidental finding during surgery in a postmenopausal patient with unspecific pelvic pain

Primary fallopian tube carcinoma (PFTC) is a rare gynecologic neoplasm and is usually diagnosed late and presents classically with a,characteristic group of symptoms. We describe a case of a 76-year-old woman who underwent TVS requested by the family physician due to unspecific pelvic pain. An adnexal mass was found with morphology associated with high levels of CA125 suggestive of a malignant tumor. During laparotomy, a mass located in the left tube was found. Histopathology confirmed PFTC. Total hysterectomy, salpingo-oophorectomy and adjuvant chemotherapy with carboplatin/paclitaxel were performed. The patient has not yet presented any signs of recurrence.

TRPV1 Expression on Peritoneal Endometriosis Foci is Associated With Chronic Pelvic Pain

Objective: To investigate the expression of capsaicin receptor (transient receptor potential vanilloid type 1 [TRPV1]) in the peritoneal endometriosis foci of women with and without chronic pelvic pain (CPP). Methods: A case-control study was conducted on 49 women with endometriosis who underwent laparoscopy, 28 of whom had CPP and 21 without CPP. Samples from peritoneum of the rectouterine excavation (2 cm(2)) were obtained by laparoscopy, fixed in 4% formaldehyde, and underwent immunohistochemistry analysis using rabbit anti-TRPV1 (1:400) polyclonal antibody. Results: Image analysis revealed that the immunoreactivity for TRPV1 was more frequent in specimens (endometriosis foci) from women with CPP (n = 15 of 28, 53.6%), compared to samples from the endometriosis foci of women without CPP (n = 6 of 21, 28.6%; P = .04). There was no correlation with duration, intensity of pain, or stage of the disease (endometriosis). Discussion: The present study shows that TRPV1 expression in peritoneal endometriosis foci is related to CPP in women. However, this association is not related to the endometriosis stage. In view of the immunoreactivity for TRPV1 observed here, we believe that some endometriotic lesions may provide a scenario for TRPV1 to be tonically active and this activity may contribute to the underlying pathology of CPP.

Comparison between the reliability levels of manual palpation and pressure pain threshold in children who reported orofacial pain

The aim of this study was to compare the intra-and inter-rater reliability of pressure pain threshold (PPT) and manual palpation (MP) of orofacial structures in symptomatic and symptom-free children for temporomandibular disorders (TMD). Fourteen children reporting pain in masticatory muscles or the temporomandibular joint and 16 symptom-free children were randomly assessed on three different occasions: by rater-1 in the first and third session and by rater-2 in the second session. The trained raters applied algometry and MP as recommended by the Research Diagnostic Criteria for TMD. Intraclass correlation coefficients and the Kappa statistic were used to assess the levels of reliability of PPT and MP, respectively. Excellent intra-and inter-rater reliability levels were observed for PPT values at most of the examined sites for symptom-free children and excellent and moderate reliability levels for children reporting pain. For MP, moderate and poor intra-rater and inter-rater reliability levels were observed for most sites in both groups. Algometry showed higher reliability levels for both groups of children and is recommended for pain assessment in children in association with MP. (C) 2010 Elsevier Ltd. All rights reserved.