Local Mepivacaine Research Articles

Implantation of a peritoneal dialysis catheter in patients with ESRD using local anesthesia and Remifentanil.

Study objectiveThe main objective of this study is to test the feasibility of the local anesthetic (LA) Mepivacaine 1% and sedation with Remifentanil as the primary anesthetic technique for the insertion of a peritoneal dialysis (PD) catheter, without the need to convert to general anesthesia.MethodsWe analyzed 27 consecutive end-stage renal disease (ESRD) patients who underwent the placement of a peritoneal catheter at our center between March 2015 and January 2019. The procedures were all performed by a general or vascular surgeon, and the postoperative care and follow-up were all conducted by the same peritoneal dialysis team.ResultsAll of the 27 subjects successfully underwent the procedure without the need of conversion to general anesthesia. The catheter was deemed prone to usage in all patients and was found to be leak-proof in 100% of the patients.ConclusionThis study describes a safe and successful approach for insertion of a PD catheter by combined infiltration of the local anesthetic Mepivacaine 1% and sedation with Remifentanil. Hereby, ESRD patients can be treated without general anesthesia, while ensuring functionality of the PD catheter.

A convenient and highly enantioselective synthesis of (S)-2-pipecolic acid: an efficient access to caine anesthetics

A novel and enantioselective synthesis of (S)-2-pipecolic acid (5) has been achieved from Oppolzer’s sultam (1) and ethyl N-(diphenylmethylene)glycinate (2) as readily available starting materials. The highly stereoselective alkylation of chiral glycine intermediate (3) with 1,4-dibromobutane afforded the key backbone of (S)-2-pipecolic acid (5) in one-step that was utilized into the preparation of the local anesthetics mepivacaine, ropivacaine and bupivacaine.

Towards an improved pain assessment in castrated horses using facial expressions (HGS) and circulating miRNAs.

Pain in horses is an emergent welfare concern, and its assessment represents a challenge for equine clinicians. This study aimed at improving pain assessment in horses through a convergent validation of existing tools: we investigated whether an effective analgesic treatment influences the horse grimace scale (HGS) and the concentration of specific circulating microRNAs (miRNAs). Eleven stallions underwent routine surgical castration under general anaesthesia. They were divided into two analgesic treatment groups: castration with the administration of preoperative flunixin and castration with preoperative flunixin plus a local injection of mepivacaine into the spermatic cords. HGS and levels of seven circulating miRNAs were evaluated pre-, 8 and 20 hours post-procedure. Compared to pre-castration, HGS, miR-126-5p, miR-145 and miR-let7e increased significantly in horses receiving flunixin at 8 hours post-castration (Friedman test, p<0.05). Both behavioural and molecular changes occurred in horses receiving flunixin only, confirming that the addition of local mepivacaine is an effective analgesic treatment. Combining the use of HGS and circulating miRNAs, particularly miR-145, could be meaningful to monitor acute pain conditions in horses. Our results further validate the HGS as a method to assess acute pain in horses and point out miR-145 as a promising biomarker to identify pain.

Efficacy comparison of intraperitoneal anaesthesia and post-operative analgesia regimens in laboratory rats.

Effective and safe anesthesia for rodents has long been a leading concern among biomedical researchers. Intraperitoneal injection constitutes an alternative to inhalant anesthesia. The aim of this study was to identify a safe, reliable, and effective anesthesia and postoperative analgesia protocol for laboratory rats exposed to painful procedures. Twenty-seven female Wistar rats in an ongoing study that required surgery were randomized into groups for three different intraperitoneal anesthesia protocols and three different analgesia regimens. The anesthesia groups were (1) medetomidine + ketamine (MK), (2) ketamine + xylacine (KX), and (3) fentanyl + medetomidine (FM). Three analgesia groups were equally distributed among the anesthesia groups: (1) local mepivacaine + oral ibuprofen (MI), (2) oral tramadol + oral ibuprofen (TI), and (3) local tramadol + oral tramadol + + oral ibuprofen (TTI). A core was assigned to measure anesthesia (0-3) and analgesia (0-2) effectiveness; the lower the score, the more effective the treatment. The mean MK score was 0.44 versus 2.00 for FM and 2.33 for KX. Mean score for analgesia on the first postoperative day was TTI (4.66) TI (9.13), and MI (10.14). Mean score 48 hours after surgery was TTI (3.4), TI (6.71), and MI (9.5). These differences were statistically significant. MK was shown to be a reliable, safe, and effective method of anesthesia. The TTI analgesia regimen is strongly recommended in light of these results.

Subcutaneous brompheniramine for cutaneous analgesia in rats

Brompheniramine as an antihistamine blocked sodium channels, and local anesthetics by blocking sodium channels produced the local anesthetic effects. The authors aimed to assess local anesthetic quality and duration of brompheniramine when compared to the local anesthetic mepivacaine. After rats were shaved and injected subcutaneously on the dorsal skin, the panniculus reflex, induced via applying a noxious pinprick to the skin (injected area), was scored. The dose-response curve and nociceptive block duration of brompheniramine were constructed and compared with mepivacaine. The cutaneous analgesic effects in both brompheniramine and mepivacaine groups were concentration-dependent. On the basis of the amount required to produce a 50% block effect (ED50, 50% effective dose), the drug's potency was brompheniramine (0.89 [0.82–0.96] μmol) better than mepivacaine (2.45 [2.17–2.76] μmol) (P < 0.01). Full recovery time of brompheniramine was more prolonged than mepivacaine's (P < 0.01) on infiltrative cutaneous analgesia when comparing ED25s, ED50s and ED75s. Our preclinical data demonstrated that subcutaneous brompheniramine induces dose-relatedly analgesic effects, and brompheniramine induces prolonged analgesic duration when compared with mepivacaine. Brompheniramine also provokes better cutaneous analgesia than mepivacaine.

Retrospective case review of combined local mepivacaine and steroid injections into vaginal trigger points for the management of moderate-to-severe perineal pain after childbirth.

After an obstetric trauma, a non-negligible number of postpartum women complain of perineal pain and dyspareunia. These symptoms clearly diminish their quality of life. Many treatment options have been suggested, such as oral analgesia, local anaesthetic, or steroid injections… Regretfully, none of these have yet demonstrated their efficacy with the validated trials. The objective of this review is to retrospectively evaluate the response to vaginal infiltrations into the trigger points (where the vaginal/perineal examination sets off the maximum intensity of pain) combining local anaesthetic and corticosteroids. Our goal is to detect women who complain of sexual disfunction and perineal pain 2 and 6months after childbirth. All reviewed cases correspond to vaginal deliveries made between June 2016 and April 2017. Trigger points were detected through a vaginal examination. Patients with moderate-to-severe perineal pain were determined using a visual analogue score (VAS 0-10). We suggested a treatment of vaginal infiltration specifically into the trigger points. Patients underwent local injections with a combination of mepivacaine hydrochloride 2% (8ml) and betamethasone acetate (2ml). Twenty-seven women were treated with vaginal injections directly into the trigger points. Seven of them [7/27 (25.92%)] were treated 2months after delivery and experienced complete recovery of their perineal pain 4months after the treatment. Those who first chose conservative treatment [20/27 (74.08%)] were also assessed 6months after giving birth. This group continued to suffer the same symptoms and they then subsequently underwent vaginal injections. As well as the first group, these women experienced complete recovery of their perineal pain after treatment. No side effects have been registered so far. Women treated with vaginal injection into the trigger points improved in a fast and effective way. It seems to be a well-tolerated and safe option for women with moderate-to-severe pain.

Spinal sensory and motor blockade by intrathecal doxylamine and triprolidine in rats.

The aim of this experiment was mainly to examine the effects of intrathecally injected doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with doxylamine or triprolidine were conducted. Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine>mepivacaine>doxylamine (P<0.05) at provoking spinal motor, proprioceptive and nociceptive blockades. On the equianaesthetic doses (ED25 , ED50 and ED75 ), the duration of spinal anaesthesia with doxylamine was longer (P<0.01) than that with mepivacaine or triprolidine. Moreover, doxylamine or triprolidine displayed greater potency (ED50 ) (P<0.05) and duration (P<0.05) of sensory block over motor block. Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective actionover motor block has a better potency than mepivacaine or doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.

2-Adamantanamine produces prolonged spinal block in rats

We aimed to investigate the local anesthetic effect of 2-adamantanamine in spinal anesthesia. The dose-response curves were constructed after intrathecally injecting the rats with five doses of 2-adamantanamine and a common local anesthetic mepivacaine. The quality and duration of 2-adamantanamine at producing spinal nociceptive, proprioceptive and motor block were compared with that of mepivacaine. We revealed that 2-adamantanamine provoked spinal nociceptive, proprioceptive and motor block dose-dependently. On the 50% effective dose (ED50) basis, the rank of potency was mepivacaine >2-adamantanamine at producing spinal nociceptive, proprioceptive and motor block (p<0.05 for the differences). 2-Adamantanamine, but not mepivacaine produced more nociceptive block than motor block (p<0.05). At the equianesthetic doses (ED75, ED50, and ED25), the nociceptive block duration caused by 2-adamantanamine was greater than that caused by mepivacaine (p<0.01 for the differences). These preclinical data showed that 2-adamantanamine is less potent than mepivacaine, while 2-adamantanamine provokes greater duration of spinal nociceptive block than mepivacaine. Furthermore, 2-adamantanamine demonstrates a more nociceptive-selective action over motor block.

Efficiency of 3% Non-epinephrine Mepivacaine Application During Intraligamentary Anesthesia With Positive and Negative Aspiration in Pain Sensitivity to Electric Current of Young Subject`s Upper Anterior Teeth Pulp:

Background: Separation methods of local anesthesia to diffuse and vascular must significantly affect the clinical effect of adrenaline containing local anesthetic (mepivacaine). The aim of this prospective, randomized, controlled studies µAde was to compare the degree of anesthesia of intact upper lateral incisor the cartridge ¼ 3% mepivacain without epinephrine in the group after the infiltration and after intraligamentary anesthesia (ILA) in the experimental group. Methods: Anesthesia performed computer syringe Sleeper One 86 subjects aged 20-23 years. In all cases, aspiration was performed. With pulp tester IVN-01 measured the pain threshold incisors and canines in microamperes during the anesthetic effect. Results: Reference level of all researched teeth (86 subjects) was ranged from 1 to 10 µA. Uniform pain threshold increase to 95 (±20) µA by 5 min. watched during infiltration anesthesia then this value gradually descended to reference level (by 20 min.). Peak single increase of pain threshold to 55 (±8,9) µA occurred immediately after 1st minute of ILA, then this value subsequently drops to reference level (10 µA) by 20 minutes. Difference between groups of infiltration and intraligamentary anesthesia (ILA+ red) and (ILA – green) presented on Chart 6. Conclusions: Infiltration anesthesia with mepivacaine without epinephrine smoothly diffusely increased the pain threshold of the front teeth, reaching a significant, maximum effect by 5 minutes. Intraligamentary injection immediately after administration created a peak increase in pain sensitivity at a lower level, almost without the participation of the diffuse component.

Chemiluminescence Determination of Local Anaesthetic Mepivacaine in Human Plasma and Pharmaceuticals.

In this study, a new method has been developed for the simple determination of mepivacaine (carbocaine). The method is based on the enhancement effect of mepivacaine in the chemiluminescence (CL) reaction of tris(1,10 phenanthroline) ruthenium(II) with cerium(IV). A mechanism for the CL reaction has been proposed on the basis of UV-Vis, fluorescent and CL spectra. Under optimum conditions, the CL intensity was proportional to the concentration of the drug in solution over the range 0.45-226.25 μg mL-1 (R2 = 0.9996). The LOD was 0.34 μg mL-1 (S/N = 3). LOD was about 10 times lower than the therapeutic concentration of mepivacaine. The percent of relative standard deviation for determination of 11 replicates at level of 9.05 μg mL-1 and 90.50 μg mL-1 of mepivacaine were 1.8 and 3.7%, respectively. The proposed method was applied successfully for the determination of mepivacaine in human plasma and injectable solutions.

Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain.

BackgroundA consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.MethodsThe efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.ResultsBy 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus.ConclusionThese findings showed that mepivacaine, rather than lidocaine, consistently attenuated two distinct symptoms of neuropathic pain and suggest that topical formulations of this local anesthetic could have utility in the alleviation of clinical HIV neuropathic pain.

Intrathecal amantadine for prolonged spinal blockade of sensory and motor functions in rats.

We aimed to compare the hypothesized local anesthetic action of amantadine (1-adamantanamine) with that of the known local anesthetic mepivacaine. Motor, proprioceptive, and nociceptive functions were evaluated in rats after intrathecal administration. Amantadine elicited spinal anesthesia in a dose-related fashion and produced a better sensory-selective action over motor blockade (P < 0.01). On the 50% effective dose (ED50 ) basis, the rank of potency on spinal motor, proprioceptive, and nociceptive block was mepivacaine > amantadine (P < 0.01 for the differences). Amantadine (63.5 μmol/kg) and mepivacaine (7.1 μmol/kg) produced complete spinal block of motor function, proprioception, and nociception. On an equipotent basis (ED25 , ED50 , and ED75 ), the duration of amantadine was longer (P < 0.01) than that of mepivacaine on spinal motor, proprioceptive, and nociceptive block. Our preclinical data demonstrated that amantadine was less potent than mepivacaine at producing spinal anesthesia. The spinal block duration produced by amantadine was greater than that produced by mepivacaine. Both amantadine and mepivacaine produced a markedly nociceptive-specific blockade.

Discriminative sensory characteristics of the lateral femoral cutaneous nerve after mepivacaine-induced block

Background and objectivesUnmyelinated C-fibres comprise the largest group of somatic afferents and have demonstrated a crucial role not only in the perception of high-threshold mechanically, thermally or chemically induced pain, but also in non-harmful low-threshold mechanical stimuli [1,2]. The objective of our study was to characterize differential sensitivity changes of C-fibre related subclasses of high-threshold and low-threshold polymodal nociceptors and low-threshold mechanoreceptors to the local anaesthetic (LA) mepivacaine during nerve block of the purely sensory lateral femoral cutaneous nerve (LFCN) in human. We assumed a diverse response of different classes of afferents to the two different concentrations of the LA mepivacaine (Scandicaine). MethodsIn a double-blind randomized experimental setting, an ultrasound-guided nerve block of the LFCN was performed in 10 healthy male subjects, each with two different concentrations of mepivacaine (0.5 and 1%). Responsiveness of afferent nerve fibres to different noxious and non-noxious stimuli was tested by Quantitative Sensory Testing (QST) 30, 180, and 300min after nerve block. Both LA concentrations of mepivacaine were compared for time course of the areas of anaesthesia for the tested sensory modalities. ResultsInitial extension of anaesthetic areas at 30min did not differ between both LA concentrations. At 180min only the anaesthetic areas to nociceptive stimuli were reduced at the site of lower mepivacaine injection (260mN: 204mm2 (18; 244; median difference and 95% confidence interval; p<0.05), heat: 276mm2 (3; 305)). In contrast, no significant differences were found between the two concentration when non-nociceptive stimuli were used (100mN: 187mm2 (4; 240), p>0.05, brush: 159mm2 (−59; 202)). ConclusionEqual initial sizes of anaesthesia areas for all sensory modalities can be explained by supramaximal perineural LA molecule concentration in both administered mepivacaine dosages. Upon washout of the LA nociceptive function is restored faster as compared to non-nociceptive sensation and higher concentration of the LA are required to maintain the analgesia. Quantitative sensory testing is able to detect different susceptibility of low threshold mechanosensors and subtypes of nociceptive C-fibres to mepivacaine. Using painful mechanical, heat and electrical stimulation different classes of nociceptors will be activated. The analgesic areas to electrical stimulation were particularly small; one might therefore hypothesize that the proposed protocol allows to also differentiate mechano-insensitive (“silent”) and mechanosensitive (“polymodal”) nociceptors. ImplicationsQST is a non-invasive method to functionally examine sensory modalities and their pharmacological modulation in humans. The method is sufficiently sensitive to differentiate the analgesic properties of mepivacaine at 0.5 and 1% and might also be adequate to different classes of nociceptors. Further development of nociceptive stimuli including supra-threshold encoding characteristics will enable to investigate peripheral analgesic effects more specifically and thus might help to design new analgesics with preferential effect on high frequency discharge of nociceptors.

Nisoxetine blocks sodium currents and elicits spinal anesthesia in rats

BackgroundAlthough nisoxetine has been shown to elicit infiltrative cutaneous local anesthesia, the inhibition of voltage-gated Na+ channels by nisoxetine has not been reported. The aim of this study was to evaluate the effect of nisoxetine on Na+ currents and its efficacy on spinal anesthesia. MethodsIn in vitro studies, the voltage-clamp method was employed to examine whether nisoxetine blocked Na+ currents in mouse neuroblastoma N2A cells. ResultsMepivacaine showed concentration- and state-dependent effect on tonic blockade of voltage-gated Na+ currents (IC50 of 3.7 and 74.2μM at holding potentials of −70 and −100mV, respectively). Nisoxetine was more potent (IC50 of 1.6 and 28.6μM at holding potentials of −70 and −100mV, respectively). In in vivo studies, after rats were intrathecally injected with nisoxetine and mepivacaine, the dose-response curves were constructed. Nisoxetine acted like local anesthetic mepivacaine and induced spinal anesthesia with a more sensory-selective action (p<0.05) over motor blockade in a dose-related fashion. Intrathecal 5% dextrose (vehicle) produced no spinal anesthesia. On the 50% effective dose (ED50) basis, nisoxetine elicited more potent spinal anesthesia than did mepivacaine (p<0.05). ConclusionsOur results showed that nisoxetine displayed a more potent and prolonged spinal anesthesia with a more sensory/nociceptive-selective action over motor blockade, compared with mepivacaine. The local anesthetic effect of nisoxetine could be probably due to the suppression of Na+ currents.

Isobolographic analysis of interaction between nisoxetine- and mepivacaine-induced spinal blockades in rats

Although nisoxetine has been shown to elicit cutaneous (peripheral) anesthesia, spinal (central) anesthesia with nisoxetine was not exposed. The aim of this study was to examine spinal anesthesia of nisoxetine and its influence on the antinociceptive action of mepivacaine. We compared nisoxetine with an established local anesthetic mepivacaine for spinal anesthesia after rats were intrathecally injected with drugs. The drugs were spinally administered alone as well as in combination, and their potencies were compared via dose-response curves and isobolographic analysis. We showed that nisoxetine, as well as mepivacaine elicited spinal anesthesia in dose-dependent manners. On a 50% effective dose (ED₅₀) basis, the spinal block effect of nisoxetine in motor function, proprioception, and nociception [0.99 (0.91-1.10), 0.85 (0.76-0.95), 0.82 (0.74-0.89)] was more potent (P < 0.05) than that of mepivacaine [1.28 (1.21-1.34), 1.14 (1.07-1.22), 0.99 (0.93-1.05)], respectively. Furthermore, the nociceptive/sensory blockade (ED₅₀) was greater than the motor blockade in both nisoxetine and mepivacaine groups (P < 0.05). Saline group (vehicle) produced no spinal anesthesia. Coadministration of nisoxetine with mepivacaine displayed an additive effect. Our data reported nisoxetine produced significant anesthesia at spinal level, and additive interaction with the local anesthetic, mepivacaine. Intrathecal nisoxetine elicited more potent spinal anesthesia than mepivacaine.

Linear scleroderma after contusion and injection of mepivacaine hydrochloride

A 36-year-old woman initially was treated for a contusion by local injection of mepivacaine hydrochloride into the left dorsum of the foot. Approximately 3 months after the injury and injection, linear sclerotic plaques originating from the site of contusion and injection were recognized. These progressed in extent and severity over a period of 3 years, when she presented to our clinic. By biopsy, swelling of collagen fibers in the lower dermis was revealed and the condition was diagnosed as linear scleroderma. Our present case had multiple linear sclerotic plaques of the left lower extremity, the distribution of which was consistent with Blaschko lines. It was also revealed that the initial sclerotic plaque was at the site of the contusion and local mepivacaine hydrochloride injection. Our present case is interesting in that the findings suggest a correlation between linear scleroderma plaque occurrence and the contusion or injection of mepivacaine.

Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites

Voltage-gated Na(+) channels (Na(v)) regulate the excitability of sensory neurons and are potential targets for novel analgesics. The secreolytic ambroxol reduces pain-related behavior in rodents and alleviates pain in humans. With properties resembling those of local anesthetics, ambroxol has been reported to block Na(+) currents in sensory neurons with a preference for tetrodotoxin-resistant (TTXr) Na(+) currents encoded by Na(v)1.8. However, the molecular determinants for ambroxol-induced block of Na(+) channels and a preferential block of Na(v)1.8 opposed to tetrodotoxin-sensitive (TTXs) Na(v) alpha-subunits have not been studied in detail. By means of whole-cell voltage clamp recordings, we studied the effects of ambroxol and local anesthetics on the recombinant TTXr subunit Na(v)1.8, on TTXs Na(v) alpha-subunits and on mutants of Na(v)1.4 that are insensitive to local anesthetics. Tonic and use-dependent block by ambroxol was strongly alleviated in local anesthetic-insensitive Na(v)1.4 mutants. Use-dependent block, but not tonic block was significantly stronger on Na(v)1.8 than on TTXs channels. The TTXs subunit Na(v)1.3 displayed the least degree of use-dependent block by ambroxol. The local anesthetics mepivacaine and S(-)-bupivacaine also blocked Na(v)1.8 and TTXs channels differentially. While mepivacaine displayed a preferential use-dependent block of Na(v)1.8, S(-)-bupivacaine displayed a preference for TTXs Na(+) channels. Our data show that ambroxol acts as a typical local anesthetic on Na(+) channels interacting with specific residues in the S6 segments. This property probably meditates the analgesic effect of ambroxol. Ambroxol preferentially blocks Na(v)1.8, however shares this property with established local anesthetics like mepivacaine.

Comparison of placental transfer of local anesthetics in perfusates with different pH values in a human cotyledon model

We aimed to investigate the placental transfer of local anesthetics in perfusates with different pH values, using a dual-perfused human cotyledon model. The dual-perfused human cotyledon model was prepared from placentas obtained following cesarean delivery (n = 5). Protein-free solution was perfused through both maternal and fetal arteries. Four amide-type local anesthetics (mepivacaine [Mep]; lidocaine [Lid]; bupivacaine [Bup]; and ropivacaine [Rop]) were added to the maternal perfusate at 1 microg ml(-1). Three conditions were tested (stage 1, maternal pH 7.4, fetal pH 7.4; stage 2, maternal pH 7.4, fetal pH 6.9; and stage 3, maternal pH 6.9, fetal pH 6.9). Venous blood samples were collected from the fetal circuit after stabilization. The fetal vein/maternal artery concentration ratio (F/M ratio) of the local anesthetics was used as an index of placental transfer. The concentration of human chorionic gonadotropin (hCG) in the maternal vein was measured at the end of each stage. The F/M ratios in all stages were in the order of: Mep > Lid > Bup [symbol: see text] Rop. The F/M ratios of Mep were significantly higher than those of the other local anesthetics in all stages. The F/M ratios of Lid were higher than those of Rop in stages 2 and 3. The F/M ratios of Lid and Rop were higher in stage 2 than in stage 3. However, the differences between the F/M ratios in the three stages were not as large as expected from the basic uncharged ([B]) condition and pH gap. The concentration of hCG showed a time-dependent decrease with increasing stage (stage 1, 81.0 +/- 58.9 mIU ml(-1); stage 2, 57.4 +/- 31.8 mIU ml(-1); stage 3, 32.1 +/- 19.7 mIU ml(-1)). Our data clearly show that it is the basic uncharged concentration that mainly determines the placental transfer of amide-type local anesthetics with protein-free perfusate. This finding suggests that Rop and Bup can be used more safely than Mep in terms of placental transfer.

New role of the trigeminal nerve as a neuronal pathway signaling brain in acute periodontitis: participation of local prostaglandins

The systemic induction of cytokines and prostaglandins plays a key role in the development of fever. However, whether fever is triggered by local injection of lipopolysaccharide (LPS) and the involvement of locally produced prostaglandins in periodontal tissue has never been assessed. Thus, we tested the hypothesis that the trigeminal nerve is a neuronal pathway that signals the brain during acute periodontitis, and this response involves prostaglandin induction. Rats were given a gingival intra-pouch injection of sterile saline or Escherichia coli lipopolysaccharide, at doses of 10 and 100 microg/kg. Some animals were pre-treated with the local anesthetic mepivacaine or had the peripheral branches of the trigeminal nerves transected. Another group of animals were pre-treated (locally or systemically) with the nonselective inhibitor of cyclooxygenases diclofenac. Body core temperature (T (b)) was measured by means of biotelemetry before and after injections. LPS elicited a dose-dependent increase in T (b), which was abolished by mepivacaine, bilateral transection of the peripheral branches of the trigeminal nerve, or local treatment with diclofenac. The results indicate that there is an activation of periodontal nerves to induce fever by LPS. It also shows that local formation of prostaglandins plays a role in fever development. Moreover, immunohistochemistry detected c-fos expression in the subnucleus caudalis of spinal trigeminal nucleus and in the preoptic area of the hypothalamus 2 and 3 h after LPS injection, further confirming the role of trigeminal nerve signaling brain in acute periodontitis.

Adjuvant local anaesthetics in the epipharyngeal space in day-case adenoidectomy: A prospective, randomized, double-blind, placebo-controlled trial

Conclusion. Mepivacaine applied in the epipharyngeal space as an adjuvant local anaesthetic does not reduce postoperative pain after adenoidectomy in children given high-dose paracetamol preoperatively. Objective. To evaluate the pain-reducing effect of an adjuvant local anaesthetic (mepivacaine) applied in the epipharyngeal space after outpatient adenoidectomy. Material and methods. This was a prospective, randomized, double-blind, placebo-controlled trial. Postoperative pain was assessed in 98 children aged 3–10 years using a visual analogue scale (VAS) and the Wong–Baker FACES pain rating scale. The time between the end of surgery and discharge from hospital was recorded, as well as the need for extra pain medication in addition to the high-dose paracetamol (acetaminophen) that had been given preoperatively. Serum levels of mepivacaine were analysed in 10 consecutive patients. Results. No difference was seen between the mepivacaine and control groups regarding postoperative pain as estimated using either the VAS or the Wong–Baker FACES pain rating scale. There were also no differences between the groups concerning the time to discharge from hospital and the need for extra pain medication before discharge. No mepivacaine could be detected in the patients’ sera.