Barriers and motivations for participation in preventive vaccine clinical trials: Experience of 5 clinical research sites.

Recruitment in preventive vaccine trials (PVT) is challenging due to common barriers to clinical research and lack of vaccine confidence. Identifying determinants of participation can help to improve recruitment. A prospective survey was conducted in 5 French clinical investigational sites. People asked to participate in a PVT were given a questionnaire whether they decided to participate or not in the trial. A total of 341 people answered the survey: 210 accepting and 131 declining to participate in a PVT. Acceptors were significantly younger (38.5 vs 54.9 years old), more likely to be involved in early phase trials, had a higher level of education (p < 0.005) and a significantly better general opinion concerning vaccines (92.3% versus 72.3%, p < 0.005) compared with those who declined. Factors associated with acceptance or refusal were evaluated in 224 people in the 4 sites where both groups were included. In a multivariate analysis, three factors: older age, having heard about PVT through multiple sources and financial incentives were significantly associated with refusal to participate in the PVT. A generally favourable opinion of vaccines was associated with acceptance. The main motivation for participation was altruism (93.2%) whereas fear of side effects was at the forefront of the barriers (36.6%). Information given by the physician was a key point for decision-making in 70.2% of those who accepted. In brief, vaccine hesitancy may decrease recruitment in PVTs; reinforcing altruism and quality of information given are key points in acceptance of participation in PVT.

Dextromethorphan Analgesia in a Human Experimental Model of Hyperalgesia.

BACKGROUND: Central pain sensitization is often refractory to drug treatment. Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models. The hypothesis is that dextromethorphan is also antihyperalgesic in humans. METHODS: This randomized, double-blind, placebo-controlled, crossover study explores the antihyperalgesic effect of single and repeated 30-mg dose of oral dextromethorphan in 20 volunteers, using the freeze-injury pain model. This model leads to development of primary and secondary hyperalgesia, which develops away from the site of injury and is associated with central sensitization and activation of N-methyl-D-aspartate receptor in the spinal cord. The primary outcome was antihyperalgesia calculated with the area under the curve of the percentage change in mechanical pain threshold (electronic von Frey) on the area of secondary hyperalgesia. The secondary outcomes were mechanical pain threshold on the area of primary hyperalgesia and cognitive (reaction time) effect. RESULTS: Single 30-mg results are reported. Antihyperalgesia (% · min) is significantly higher on the area of secondary hyperalgesia with dextromethorphan than placebo (median [interquartile range]: 3,029 [746; 6,195] vs. 710 [-3,248; 4,439], P = 0.009, Hedge's g = 0.8, 95% CI [0.1; 1.4]). On primary hyperalgesia area, mechanical pain threshold 2 h after drug intake is significantly higher with dextromethorphan (P = 0.011, Hedge's g = 0.63, 95% CI [0.01; 1.25]). No difference in antinociception is observed after thermal painful stimuli on healthy skin between groups. Reaction time (ms) is shorter with placebo than with dextromethorphan (median [interquartile range]: 21.6 [-37.4; 0.1] vs. -1.2 [-24.3; 15.4], P = 0.015, Hedge's g = 0.75, 95% CI [0.12; 1.39]). Nonserious adverse events occurrence (15%, 3 of 20 volunteers) was similar in both groups. CONCLUSIONS: This study shows that low-dose (30-mg) dextromethorphan is antihyperalgesic in humans on the areas of primary and secondary hyperalgesia and reverses peripheral and central neuronal sensitization. Because dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-D-aspartate receptor may need to be sensitized by pain for dextromethorphan to be effective.

Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial.

BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

[Why and how to perform an ultrasound-guided transversus abdominis plane block: A step-by-step approach]. / Le TAP block échoguidé pas à pas : pourquoi et comment le réaliser ?

Used in clinical practice as part of a multimodal analgesic regimen, the transversus abdominis plane block (TAP block) is a relative novel procedure in which local anaesthetic agents are injected into the anatomic neurofascial space between the internal oblique and the transversus abdominis muscle. It allows a significantly prolonged duration of analgesia during the early postoperative stage in abdominal surgery. This regional anesthesia technique provides analgesia to the skin, muscles of the anterior abdominal wall and parietal peritoneum in order to decrease the incision-related pain. Thus, it reduces postoperative opiate requirements and opioids-related side effects (nausea, vomiting, delayed resumption of intestinal transit, drowsiness, respiratory depression, urine retention). Additionally, the TAP block appears particularly interesting when neuraxial techniques or opioids are contraindicated. Moreover, the ultrasound-guided procedure provides a significant success rate of this block and additionally avoids major complications. We describe our technique of ultrasound-guided TAP block and discuss its indications, contraindication and potential complications.

Local anaesthetic infiltration at the end of carotid endarterectomy improves post-operative analgesia.

BACKGROUND: Wound infiltration at the end of carotid endarterectomy under general anaesthesia is a simple technique that can be delegated to the surgeon. It was hypothesised that this technique could improve early post-operative analgesia by reducing the need for post-operative opioids. METHODS: Forty patients underwent carotid endarterectomy under general anaesthesia with desflurane and remifentanil supplemented with morphine for post-operative analgesia. In a prospective double-blinded randomised study, patients were allocated pre-operatively to receive either subcutaneous infiltration of both wound edges with 20 ml of 0.75% ropivacaine or infiltration with isotonic saline. The primary outcome was morphine consumption while in the post-anaesthesia care unit (PACU). Pain scores at rest and movement, sedation, and patient satisfaction were the other main outcomes used to assess post-operative analgesia. RESULTS: The median dose of morphine administered in the PACU was 2 mg [0-3] in the ropivacaine vs. 4 mg [3-6] in the placebo group (P = 0.0004, Mann-Whitney's test). Pain at rest and at movement was lower in the ropivacaine group throughout observation in the PACU. No difference was found for both pain and opioid consumption after discharge from the PACU or for patient satisfaction. Sedative events in the early post-operative period were less frequent in the ropivacaine group. CONCLUSIONS: Local anaesthetic wound infiltration performed before closure reduces the need for additional opioids, lowers the immediate post-operative pain and improves alertness. These results argue for the use of local infiltration anaesthesia for carotid endarterectomy.

[Comparison of two opioids with different kinetics for intravenous analgesia in outpatient multiple third molar avulsions]. / Comparaison de deux opioïdes de cinétique différente dans l'analgésie intraveineuse pour avulsion des dents de sagesse en ambulatoire.

INTRODUCTION: We had for aim to compare the effects of intra-operative opioid analgesia according to the drug kinetics. PATIENTS AND METHODS: We conducted a prospective, controlled, randomized, double-blinded trial including 60 patients scheduled for ambulatory multiple third molar avulsion. The general anesthesia, performed with propofol and analgesia was a target-controlled infusion of either remifentanil or sufentanil. The anesthesia was set to reach an optimal bispectral index and adjusted to a clinical target throughout the procedure. The main endpoints were: postoperative request for morphine and other opioids; postoperative pain; postoperative adverse effects of opioids. RESULTS: In the post-operative care unit (French acronym PACU), patients who received remifentanil were extubated earlier (17 vs. 26 min.), but had more pain and required twice more morphine for analgesia (6 vs. 3 mg), than those who had received sufentanil. However, the need for post-surgery oral opioid intake was greater in the sufentanil group, so the overall postoperative opioid consumption and patient satisfaction were identical in both groups. The time spent in the PACU was also identical for both groups. DISCUSSION: Using an ultra-short kinetic opioid such as remifentanil does not seem useful, since the shorter delay before extubation is compensated by a greater need for morphine in the PACU.

[A French survey on the practice of analgesia for thoracic surgery]. / Enquête sur les pratiques françaises d'analgésie en chirurgie thoracique (réalisée avec le concours de l'ARCOTHOVA).

OBJECTIVE: To assess the current practice of analgesia after thoracotomy and thoracoscopy in France. STUDY DESIGN: Cross-sectional practice survey. MATERIAL: Anaesthetist physicians, each referent for one of the French centres practicing thoracic surgery, during year 2012. METHODS: Electronic questionnaire about the activity of the centre in thoracic surgery, and modalities and estimated frequencies of different analgesic techniques. Primary assessment was the estimated percentage of acts, after imputation from original data. RESULTS: Eighty-four centres out of 103 (82 %) answered the questionnaire. Coupling locoregional to general anaesthesia involved 74 % of thoracotomies and 35 % of thoracoscopies. A practice (i.e. for more than 5 % of patients) of epidural analgesia was declared by 68 centres (81 %), and by 27 centres (32 %) for paravertebral block. The most current practices for epidural analgesia were: thoracic puncture, intraoperative initiation, ropivacaïne 0.2 % plus sufentanil, patient-controlled administration with infusion plus bolus, application more than 48hrs post surgery. The practice rates for technique of paravertebral block were: Eason & Wyatt 34 %, ultrasound-guided 24 %, internal 42 %. The most frequent systemic analgesia was patient-controlled intravenous morphine. Ketamine was used in 60 % of the cases. CONCLUSIONS: French practice of analgesia after thoracic surgery improved quality during the last decade, but more than one patient on four (compared to 8 % in UK) may have neither epidural nor paravertebral block, while such techniques are nowadays considered as standard.

Addition of clonidine to a continuous patient-controlled epidural infusion of low-concentration levobupivacaine plus sufentanil in primiparous women during labour.

We studied the potentiation of analgesia for labour by the addition of clonidine to epidural low-concentration levobupivacaine with sufentanil in a randomised, double-blinded study. We enrolled primiparous women who were in spontaneous labour. The study solutions, made of 100 ml levobupivacaine 0.0625% plus sufentanil 0.45 µg.ml(-1) and either 150 µg clonidine or no clonidine, were used for induction of analgesia, and for its maintenance with self-administered boluses and a continuous background infusion. The need for additional epidural boluses during labour was lower and analgesia and maternal satisfaction were better in the clonidine (n = 57) than in the control group (n = 58). Blood pressure was lower and the rate of instrumental delivery higher in the clonidine group. Clonidine (1.36 µg.ml(-1)) added to the epidural solution of low-concentration levobupivacaine improves the quality of analgesia. The relevance of the haemodynamic effects should be explored in larger validation studies.

[Post-partum haemorrhage in delivery room: anaesthetists' practioner in Auvergne]. / Hémorragie du post-partum en salle de naissance : pratique déclarée des anesthésistes en région Auvergne.

OBJECTIVE: To assess the management of post-partum haemorrhage (PPH) in delivery rooms by the anaesthetists of the Auvergne region. STUDY DESIGN: Cross sectional study. METHODS: An anonymous postal survey was sent to all the anaesthetists working in a public or private hospital with a maternity unit. RESULTS: The response rate was about 70 %. Eight percent of the respondents never practiced in obstetrics; others all declared to have managed PPH at least once. Only 66 % declared to know the right definition of PPH, 98 % declared to have guidelines in the delivery room, 87 % to use graduate blood receipt pockets, 85 % to work under midwives-directed delivery at expulsion, 88 % to have a HemoCue™ system. More than 80 % declared to use first oxytocin and to switch for prostaglandins in case of failure, to put two venous catheters and a urinary catheter, to administer broad-spectrum prophylactic antibiotic and to draw a blood sample for early biology. Packed red cells, platelets and fresh frozen plasma were accessible in less than 30 minutes for 98 %. Transfusion guidelines were applied. Only 27 % could have arterial radiologic embolisation on site. The knowledge about PPH and its consensual care tended to be poorer in practitioners from the university hospital, and younger under 40 also. CONCLUSION: This survey, with a good response rate, showed a practice generally fitting to the guidelines, although with some failures depending on the practioner's age and type of hospital.

Continuous patient-controlled epidural infusion of levobupivacaine plus sufentanil in labouring primiparous women: effects of concentration.

The effects of two different concentrations of epidural levobupivacaine were compared when used to provide analgesia for labour. Primiparous women in spontaneous uncomplicated labour were enrolled in a prospective, randomised and partially double-blinded study. The study solutions were either 0.568 mg x ml(-1) levobupivacaine (low concentration group) or 1.136 mg x ml(-1) levobupivacaine (high concentration group), with sufentanil 0.45 microg x ml(-1) added to both solutions. Epidural analgesia was initiated with 20 ml of the study solution, followed by a standardised algorithm of top-up bolus injections. Epidural analgesia was then continued by self-administered boluses of 5-ml plus a continuous infusion of 5 ml x h(-1). Analgesia was found to be more efficacious in the high-concentration group. The dose of levobupivacaine administered was higher and sometimes overstepping recommended limits in the high concentration group, but with no observed increase in side-effects. The choice between these two concentrations may still be made according to the patient's and the practitioner's preferences. The effects of an intermediate concentration should be studied in the future.

Harmonisation of ethics committees' practice in 10 European countries.

BACKGROUND: The Directive 2001/20/EC was an important first step towards consistency in the requirements and processes for clinical trials across Europe. However, by applying the same rules to all types of drug trials and transposing the Directive's principles into pre-existing national legislations, the Directive somewhat failed to meet its facilitation and harmonization targets. In the field of ethics, the Directive 2001/20/EC conditioned the way of understanding and transposing the "single opinion" process in each country. This led to a situation in which two models of research ethics committees organisation systems exist, being the model in which the "single opinion" is considered to be the decision made by a single ethics committee more effective and simpler in terms of administrative and logistic workload. METHOD: A survey was conducted in 10 European countries. Members of the European Clinical Research Infrastructures Network working party number 1, with expertise in the field of ethics, responded. RESULTS: There is a major heterogeneity in the composition of ethics committees among the surveyed countries based on the number of members, proportion of experts versus lay members and expertise of the scientific members. A harmonized education of the ethics committees' membership based in common curricula is recommended by the majority of countries. CONCLUSIONS: Despite the efforts for harmonization of the European Clinical Trial Directive, from an ethical point of view, there remains a plurality of ethics committees' systems in Europe. It is important to comprehend the individual national systems to understand the problems they are facing.

An in-use microbiological comparison of two surgical hand disinfection techniques in cardiothoracic surgery: hand rubbing versus hand scrubbing.

Surgical site infection after heart surgery increases morbidity and mortality. The method of presurgical hand disinfection could influence the infection risk. From February to April 2003, we compared the microbiological efficacy of hand-rubbing (R) and hand-scrubbing (S) procedures. The surgical team alternately used hand-scrubbing or hand-rubbing techniques every two weeks. Fingertip impressions were taken before and immediately after hand disinfection, every 2h and at the end of the operation. Acceptability of hand rubbing was assessed by a questionnaire. Mean durations of surgical procedures were 259+/-68 and 244+/-69min for groups S and R respectively (P=0.43). Bacterial counts immediately after hand disinfection were comparable with the two techniques, but significantly lower in group R at the end of surgery. No differences were observed between the percentages of negative samples taken after 2h, 4h and at the end of surgery between the two groups. Bacterial skin flora reduction immediately after hand disinfection, after 2h and 4h of operating time and at the end of surgery was better in group R, but the difference was not statistically significant. Before surgery, the hand-rubbing method with alcohol solution preceded by hand washing with mild neutral soap is as effective as hand scrubbing to reduce bacterial counts on hands. It decreased the bacterial counts both immediately after hand disinfection and at the end of long cardiothoracic surgical procedures. The acceptability of hand rubbing was excellent and it can be considered to be a valid alternative to the conventional hand-scrubbing protocol.

Comparison of tolerance of facemask vs. mouthpiece for non-invasive ventilation.

This prospective, single centre, randomised, cross-over study compares patient tolerance of the facemask and mouthpiece for delivery of non-invasive ventilation in an intensive care unit. Twenty-seven patients with acute respiratory failure were scheduled for two 45-min sessions of non-invasive ventilation with facemask and mouthpiece. The order of the sessions was chosen at random. Nurses and patients assessed the tolerance of both techniques using a visual analogue scale. The time spent by nurses and the changes in respiratory parameters were recorded. The facemask was better tolerated than the mouthpiece; all the cases of non-invasive ventilation withdrawal (n = 5) occurred with mouthpieces (p = 0.026). Less nursing time was required using the facemask for the 22 patients who underwent both procedures (p = 0.01). However, the difference in tolerance scores was not significant. Non-invasive ventilation with both facemask and mouthpiece improved the P(a)o(2)/F(i)o(2) ratio, increased the pH and decreased the P(a)co(2). Only non-invasive ventilation with the facemask lowered the respiratory rate. The facemask appears to be a better initial choice for non-invasive ventilation when compared to mouthpiece, but both can be effective.

Modifications of spontaneous cerebral blood flow oscillations during cardiopulmonary bypass.

UNLABELLED: Spontaneous slow waves are present in the systemic circulation including the intracranial compartment. They are supposed to reflect the cerebral autoregulation. We hypothesised that in the absence of cardio respiratory variability, during cardiopulmonary bypass (CPB), we should reveal extreme physiologic controls. MATERIAL/METHODS: Ten patients were included. Arterial blood pressure (ABP, radial invasive), extracorporeal circuitry pressure and cerebral blood flow velocity (CBFV, middle cerebral artery) were recorded. We analysed the slow waves in the B (8 to 50) and the UB (>50 to 200) bands (in milli-Hz). The analysis, before and during CPB, was performed in the tine domain (correlation coefficient, entropy, mean quantity of mutual information, relative entropy) and in the frequency domain (spectrogram, frequency spectrum, coherence). RESULTS: CPB dramatically changed monitored signals decreasing their entropy and revealing a dominant CBFV 70 mHz-frequency and a dominant ABP 9 mHz-frequency. There was no association between the signals (p < 0.05). Before CPB we found complex patterns where B and UB waves were present. CONCLUSION: We hypothesised that CPB provoked a highly protective mechanism, reducing the fluctuations of CBF, by a deactivation of B waves, revealing monotonous UB waves.

Perispinal analgesia for labour followed by patient-controlled infusion with bupivacaine and sufentanil: combined spinal-epidural vs. epidural analgesia alone.

BACKGROUND AND OBJECTIVE: Combined spinal-epidural is an alternative technique to epidural analgesia for labour, but its benefits are not clearly identified. METHODS: A prospective, blinded, randomized study was undertaken involving 113 women attending a university hospital obstetric department. Analgesia was initiated with intrathecal bupivacaine 0.25% 1 mL + sufentanil 5 microg in the combined spinal-epidural group (n = 54), and with bupivacaine 0.125% + epinephrine 2.5 microg mL(-1) + sufentanil 7.5 microg in the epidural group (n = 59). In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125% (+ sufentanil 0.25 microg mL(-1)). Duration of labour, quality of analgesia and side-effects were compared between groups. RESULTS: In the combined spinal-epidural group, the onset of analgesia was faster (5 vs. 15 min, P < 0.001), the consumption of bupivacaine was lower (7.5 vs. 11.3 mg h(-1), P = 0.003) and there was less unilateral analgesia (14.8% vs. 40.7%, P = 0.002) than in the epidural group. The characteristics of labour were similar in both groups. However, in the combined spinal-epidural group, there was a higher incidence of posterior presentation (25.9% vs. 10%, P = 0.03), pruritus (P < 0.001), hypotension (P = 0.002), somnolence (P = 0.01), nausea (P = 0.02) and one case of meningitis. CONCLUSIONS: The combined spinal-epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage. It induced more adverse effects and this should be considered before routinely using the combined spinal-epidural technique.

Epidural versus intrathecal morphine for postoperative analgesia after Caesarean section.

BACKGROUND: Perispinal anaesthesia for Caesarean section allows injection of epidural (ED) or intrathecal (i.t.) morphine to provide long-lasting postoperative analgesia. To compare these two routes, a prospective, randomized, double-blinded study of 53 patients undergoing elective Caesarean section was performed. METHODS: Combined spinal-epidural anaesthesia with 6 mg of i.t. hyperbaric bupivacaine plus sufentanil 5 microg, and additional ED lidocaine was used. Additionally, each patient received either 2 mg (2 ml) of ED morphine plus 1 ml of i.t. normal saline (ED group, n=28), or 0.075 mg (1 ml) of i.t. morphine plus 2 ml of ED normal saline (i.t. group, n=25). Additional postoperative analgesia was given in the form of propacetamol and ketoprofen, plus self-administered i.v. morphine. RESULTS: No major respiratory depression occurred. Time to first demand of morphine was similar in the ED (307.5 min) and i.t. (310 min) groups, as was the incidence of side-effects such as sedation, pruritus, nausea, and vomiting. During the first 24 postoperative hours, VAS pain scores were greater in the i.t. group (P=0.032), as was additional morphine consumption (4 vs 1.5 mg) (P=0.03). CONCLUSIONS: The ED protocol was more effective than the i.t. protocol, whilst side-effects were similar.

[Physiopathologic consequences of laparoscopic surgery]. / Conséquences physiopathologiques de la chirurgie coelioscopique.

The aim of this present review was to study the effects of the intraperitoneal carbon dioxide insufflation, on the different physiological functions in order to prevent or to treat the side effects or complications which may occur in laparoscopic surgery. The major data from literature are confronted with the practical knowledge from a group of anesthetists with large experience in gynecological laparoscopic surgery.

Systemic morphine reduces the wind-up of trigeminal nociceptive neurons.

We assessed the effects of intravenous morphine on the wind-up of nociceptive neurons of the spinal trigeminal nucleus oralis (Sp5O). Extracellular recordings of Sp5O nociceptive convergent neurons were performed in intact halothane-anesthetized rats. Wind-up of C-fiber-evoked responses was elicited by repetitive electrical stimulation (train of 16 shocks, 0.66 Hz) of their receptive field at C-fiber intensity (3 times the threshold). Wind-up was tested for its sensitivity to morphine (6 mg/kg,i.v.), and the specificity of the effects was verified with naloxone (0.4 mg/kg, i.v.). Nineteen convergent neurons displaying wind-up were recorded. Morphine reduced the wind-up of all but one. In five cases, notwithstanding a reduced wind-up, the neuronal response evoked by the first stimulus in the train (initial input) was unexpectedly increased. Naloxone always antagonized morphine inhibitory effects on the wind-up. When administered systemically, morphine reduced the wind-up of trigeminal nociceptive neurons. This inhibitory effect occurred independently of morphine's ability to affect the initial C-fiber-evoked input. Our findings support the idea that systemic morphine probably blocks wind-up by acting at opioid receptors located postsynaptically to nociceptive primary afferents.

Stimulus-function, wind-up and modulation by diffuse noxious inhibitory controls of responses of convergent neurons of the spinal trigeminal nucleus oralis.

Extracellular unitary recordings were made from 53 spinal trigeminal nucleus oralis (Sp5O) convergent neurons in halothane-anaesthetized rats. The neurons had an ipsilateral receptive field including mainly oral or perioral regions. They responded to percutaneous electrical stimulation with two peaks of activation. The first had a short latency (4.3 +/- 0.3 ms) and low threshold (0.35 +/- 0.04 mA), whereas the second had a longer latency (68.1 +/- 3.4 ms) and higher threshold (7.3 +/- 0.5 mA). Intracutaneous injection of capsaicin (0.1%) produced a strong and rapid reduction of the long-latency responses of Sp5O convergent neurons with little effect on the short-latency responses. In most cases (73%), the long-latency responses exhibited a wind-up phenomenon during repetitive (0.66 Hz) suprathreshold electrical stimulation. These results suggest that C-fibres mediate the long-latency response of Sp5O convergent neurons. Regarding the C-fibre-evoked responses, a linear relationship between the intensity of the applied current and the magnitude of the response was found within the one to three times threshold range. The Sp5O convergent neurons also encoded the intensity of mechanical stimuli applied to the skin or mucosa in the 5-50 g ranges. The evoked activity of Sp5O convergent neurons could be suppressed by noxious heat applied to the tail (52 degrees C) and long-lasting poststimulus effects followed this. These findings show that convergent neurons in the Sp5O resemble those in the deep laminae of the spinal dorsal horn and spinal trigeminal nucleus caudalis, and further support that the Sp5O plays a part in the processing of nociceptive information from the orofacial region.

Effects of lesions in the trigeminal oralis and caudalis subnuclei on different orofacial nociceptive responses in the rat.

Behavioural responses to two different orofacial noxious stimulations were analysed following lesion of spinal trigeminal subnucleus oralis (Sp5O) in the rat. Lesions were obtained by intranuclear microinjections of quinolinic acid (0.4 microliter of 60 nmol/microliter solution). The control groups received microinjection of saline. Noxious stimulation was a subcutaneous injection of formalin into the upper lip or electrical stimulation of the tooth pulp. The measured behavioural responses were duration of rubbing induced by the formalin injection and thresholds of the jaw-opening reflex (JOR), head rotation (HR) and face rubbing (FR) evoked by the pulp stimulation. In addition, formalin injection was also performed in two groups of rats that had received intranuclear injection of quinolinic acid or saline into rostral subnucleus caudalis (Sp5C). Rubbing duration was not significantly modified by the lesion of Sp5O, whereas a significant decrease occurred after the lesion of rostral Sp5C. After the lesion of Sp5O, an increase in the threshold of JOR was observed whereas the thresholds of HR and FR were not significantly modified. These results suggest that Sp5O is not necessary for the processing and relay of nociceptive inputs triggered by intense stimulations of oral and perioral areas. However further experiments are needed to reconcile these results with the relevant data obtained from cell recording experiments which indicate the existence, in Sp5O, of neuronal activities related to the sensory discriminative aspect of intense nociception.