The efficacy of injecting a distillate of the pitcher plant (Sarraceniaceae) adjacent to the palmar digital nerves of horses to ameliorate lameness caused by digital pain.

This study aimed to determine the efficacy of instilling extract of the pitcher plant around the palmar digital nerves of horses to ameliorate digit pain causing lameness. Five mixed breed horses were recruited. Horses were determined to be lame because of pain in the distal portion of one or both thoracic limbs by a positive response to a basisesamoid nerve block using 2%^mepivacaine hydrochloride. Gait was evaluated pre- and post-nerve block at 30 min, 3, 7,14 and 21 days. At the 3-week evaluation, the basisesamoid nerve block was repeated using the extract, and the gait was evaluated at similar times. Lameness was evaluated objectively using a wireless, inertial, sensor-based, motion analysis system. The basisesamoid nerve block significantly ameliorated lameness at 30 min when gait was evaluated, but it had no significant effect on lameness after this time. The product containing extract of the pitcher plant had no significant effect on lameness when administered as a basisesamoid nerve block at any time. Extract of the pitcher plant administered adjacent to the medial and lateral palmar digital nerves (i.e., a basisesamoid nerve block) had no efficacy in ameliorating lameness in the distal portion of one or both thoracic limbs. Extract of the pitcher plant likely has no value for treating horses for chronic pain when administered as a regional nerve block.

Modified abaxial sesamoid nerve block provides enhanced proximal diffusion compared to basisesamoid block and lower proximal diffusion than traditional low plantar nerve block in equine hind limbs: ex vivo and in vivo study.

OBJECTIVE: To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. SAMPLE: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. METHODS: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block (TLPB). Ten minutes after injection, skin was dissected and proximal diffusion distance of the dye patch was measured. In the in vivo model, both hind limbs were injected with radiopaque contrast medium with either MASB or TLPB. Ten minutes after injection, a radiograph was acquired and the proximal diffusion of the contrast medium patch was measured. RESULTS: In the ex vivo model, solution proximal diffusion distance for MASB was significantly longer than BSB (P < .050) and significantly shorter than TLPB (P < .050). Both techniques reached the proximal aspect of DFTS similarly (P = .289), and no difference in the incidence of intrasynovial or intravascular injections was observed (P = .292). In the in vivo model, contrast medium proximal diffusion of MASB was significantly shorter than TLPB (P < .050). The proportion of injections that diffused subcutaneously to the proximal aspect of the proximal pouch of the DFTS was not significantly different between techniques (P = .136). No difference in the incidence of DFTS intrasynovial or intravascular injections was observed (P = .305). CLINICAL RELEVANCE: MASB presented significantly more proximal diffusion than BSB and less proximal diffusion than TLPB, consistently reached the proximal aspect of DFTS, and presented a very low risk of intrasynovial and intravascular injections.

Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. STUDY DESIGN: Randomized, masked, crossover study. ANIMALS: Twelve healthy adult mares. METHODS: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals until it returned to baseline. Ocular examinations were performed at 24-, 72, and 168 h post-injection to monitor for adverse effects. RESULTS: The mean total time of anesthesia (TTA) was 168.3 min for ropivacaine, 169.2 min for liposomal bupivacaine, 103.3 min for mepivacaine and 30.7 min for the control. TTA for liposomal bupivacaine (p < .001) and ropivacaine (p = .001) was longer than the control. TTA for mepivacaine was not different from the control (p = .138), liposomal bupivacaine (p = .075) or ropivacaine (p = .150). Injection site hemorrhage reduced TTA regardless of treatments (p = .047). No adverse effects attributed to injections were noted. CONCLUSION: All three medications were well tolerated. Subconjunctival administration of ropivacaine and liposomal bupivacaine resulted in longer TTAs compared to the control; however, their TTAs were not different from that of mepivacaine. CLINICAL SIGNIFICANCE: Subconjunctivally administered liposomal bupivacaine and ropivacaine are viable options to provide prolonged corneal analgesia in horses. Future studies are needed to assess the efficacy in diseased eyes.

MicroRNA-27a Suppresses the Toxic Action of Mepivacaine on Breast Cancer Cells via Inositol-Requiring Enzyme 1-TNF Receptor-Associated Factor 2.

Objective: To investigate the toxic effects of microRNA-27a on breast cancer cells through inositol-acquiring enzyme 1-TNF receptor-associated factor 2 inhibition by mepivacaine. Methods: The elevation of miR-27a in MCF-7 of BCC lines was measured, and groups were set up as control, mepivacaine, and elevated groups. Cells from each group were examined for inflammatory progression. Results: Elevated miR-27a in MCF-7 cells was able to distinctly augment the cell advancement (P < 0.01) and decline cell progression (P < 0.01). Meanwhile, miR-27a reduced the content of intracellular inflammatory factors IL-1ß (P < 0.01) and IL-6 (P < 0.01), elevated the content of IL-10 (P < 0.01), suppressed levels of cleaved-caspase-3 and p-signal transducer and activator of transcription-3 (STAT3) (P < 0.01), and increased Bcl-2/Bax (P < 0.01). Conclusion: Elevated miR-27a in MCF-7 of BCC lineage was effective in reducing the toxic effects of mepivacaine on cells and enhancing cell progression. This mechanism is thought to be related to the activation of the IRE1-TRAF2 signaling pathway in BCC. The findings may provide a theoretical basis for targeted treatment of BC in clinical practice.

Comprehensive Analysis of Local Anesthetics Affecting Adipose Stem Cells In Vitro.

BACKGROUND: Adipose stem cells (ASCs) hold a great regenerative capacity because of their differentiation capability and their secretory activity. Thus, ASC survival is of great significance during perioperative harvesting. Various local anesthetics are commonly applied during fat grafting procedures. These substances are known to impair cellular viability, which would affect graft survival and final outcomes, but the exact extent of their impact on ASC biology is unknown. METHODS: The authors analyzed the short- and long-term effects of lidocaine, mepivacaine, ropivacaine, and bupivacaine at increasing concentrations (0.1 to 10 mM) on primary human ASC proliferation and metabolic activity. Trilinear differentiation was assessed by oil red O stain (adipogenesis), safranin O (chondrogenesis), and cresolphthalein (osteogenesis) labeling. In supernatants, cytokine [interleukin (IL)-6/IL-8, vascular endothelial growth factor, hepatocyte growth factor] secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS: Bupivacaine at greater than 100 µM demonstrated the strongest anti proliferative effects, whereas lidocaine and ropivacaine did not affect cell numbers. Mepivacaine evoked reciprocal results regarding cell count at greater than 1 mM. Each compound impaired trilinear differentiation. Secretion of hepatocyte growth factor and IL-8 was reduced significantly by local anesthetic exposure; levels were restored after substances were washed out. CONCLUSIONS: In vitro data show that lidocaine, mepivacaine, and ropivacaine could be applied at concentrations of 1 to 10 mM without affecting ASC survival. In contrast, bupivacaine at concentrations greater than 100 µM should be administered with great caution. The differentiation of ASCs and the ASC's secretome might already be decreased by each local anesthetic at 1 mM. CLINICAL RELEVANCE STATEMENT: The authors' experimental data can be of great significance to the clinical practice, as local anesthetics are routinely administered during liposuction as a tumescent anesthesia adjunct. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Intrathecal mepivacaine after general anesthesia is an effective method of equine euthanasia when compared to intravenous pentobarbital.

OBJECTIVES: This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous injection of pentobarbital in sedated horses. ANIMALS: Client-owned horses and horses requiring euthanasia due to involvement in concurrent research projects were used. Horses were randomly assigned to 1 of 2 groups: intrathecal mepivacaine after anesthesia or intravenous pentobarbital after sedation. All horses had normal vital parameters and no signs of infectious disease at the time of euthanasia. PROCEDURES: The intrathecal mepivacaine group was anesthetized before the intrathecal injection of mepivacaine. The pentobarbital group was sedated, concurrently anesthetized and euthanized using intravenous pentobarbital, then received an intrathecal saline (0.9% NaCl) solution injection to a blind observer. Both groups were sedated with detomidine and the time from sedation to the cessation of vital parameters (respirations, pulse, corneal reflex, and ECG) was recorded. Euthanasias were recorded for review by a blinded anesthesiologist, using an independent scale to assess the quality of sedation, anesthesia induction, and lateral recumbency. RESULTS: Time from detomidine administration to cessation of each vital parameter was significantly longer in the intrathecal mepivacaine group. There was no statistically significant difference in qualitative scores between groups for sedation or induction, but lateral recumbency was subjectively superior in the anesthetized intrathecal mepivacaine group. CLINICAL RELEVANCE: Intrathecal mepivacaine provided a safe, effective, alternative method of euthanasia to intravenous pentobarbital and addresses concerns about barbiturate availability. This study also informs practitioners of what to expect (ie, longer cessation of vital parameters) when using the intrathecal mepivacaine method.

Comparison of 2% mepivacaine and a solution of 2% lidocaine/epinephrine administered for median and ulnar nerve blocks in horses with naturally occurring forelimb lameness.

OBJECTIVE: To compare a 2% lidocaine solution containing 5 µg/ml (1:200 000) epinephrine with 2% mepivacaine for reducing lameness in horses after use in proximal nerve blocks. STUDY DESIGN: Experimental randomized crossover. ANIMALS: Six adult horses with naturally occurring forelimb lameness. METHODS: Horses were evaluated using an inertial gait sensor system. Lameness was measured as a vector sum (VS). Following baseline lameness examination, median and ulnar nerve blocks were performed with lidocaine/epinephrine (0.5 mg epinephrine added to 50 ml of 2% lidocaine immediately prior to administration) or an equal volume of 2% mepivacaine. Horses were trotted at 5 min and then at 30 min intervals for 150 min. After 24 h, nerve blocks were repeated using the other local anesthetic. Data were evaluated using linear models. RESULTS: The reduction in the VS did not differ after nerve blocks with lidocaine/epinephrine or mepivacaine (P = .791). Mean time to VS <8.5 mm (n = 5) was 5 and 9.6 min for lidocaine/epinephrine and mepivacaine, respectively. For one horse, VS was not reduced to <8.5 mm with either treatment (this horse had the highest VS before treatments were administered). The decrease in VS to <8.5 mm lasted for 150 min in both treatment groups. CONCLUSION: The outcomes of the median and ulnar nerve blocks performed with 2% lidocaine with epinephrine did not differ from blocks performed with 2% mepivacaine. CLINICAL RELEVANCE: Two percent lidocaine with epinephrine may serve as an adequate replacement for proximal nerve blocks when mepivacaine is unavailable.

Dexmedetomidine prolongs the duration of action of mepivacaine on anesthesia of the palmar digital nerves of horses.

OBJECTIVE: To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone. ANIMALS: 8 mares with no signs of lameness. PROCEDURES: In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexmedetomidine. Each horse received each treatment, and treatments were administered ≥ 2 weeks apart. The mechanical nociceptive threshold was measured at a region between the heel bulbs with the use of a digital force gauge before (baseline) and at 15-minute intervals after treatment. RESULTS: The mean duration of sensory blockade of the digit was 2-fold longer when a combination of mepivacaine and dexmedetomidine was administered (371 minutes), compared with when mepivacaine alone was administered (186 minutes). Treatment with dexmedetomidine alone did not change the mechanical nociceptive threshold substantially from baseline and resulted in no clinical signs of sedation. CLINICAL RELEVANCE: Results indicated that relief from digital pain provided by perineural treatment with mepivacaine for PDN blockade can be extended by adding dexmedetomidine to the injectate.

MicroRNA-183-5p protects human derived cell line SH-SY5Y cells from mepivacaine-induced injury.

With the gradual recognition of the side effects of local anesthetics, the nerve injury caused by local anesthetics has received growing attention. This research intended to delve into miR-183-5p changes in mepivacaine-mediated SH-SY5Y cell injury, as well as its modulatory mechanism on cell apoptosis. RT-qPCR was adopted for assaying miR-183-5p and PDCD4 mRNA expression. Our team respectively transfected miR-183-5p mimic and inhibitor to enhance or inhibit miR-183-5p function. We employed Western blot for detecting PDCD4 protein levels, as well as flow cytometry and Hoechst 33342/PI double staining for determining cell apoptosis rate. Additionally, our crew applied an ELISA kit for measuring TNF-α, IL-1ß, IL-6, and IL-8 contents. The level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection Kit. As well as dual-luciferase reporter experiment for verifying the targeting link of miR-183-5p with PDCD4. In mepivacaine-induced cell apoptosis in SH-SY5Y cells, miR-183-5p expression was down-regulated. TNF-α, IL-1ß, IL-6, and IL-8 contents were elevated. The rate of apoptosis increased visibly, cleaved caspase-3 and Bax levels waxed, whereas Bcl-2 level waned. MiR-183-5p could alleviate the damaging impact of mepivacaine. Dual-luciferase reporter experiments demonstrated that miR-183-5p directly targeted PDCD4. Collectively, we concluded that a high concentration of mepivacaine can cause SH-SY5Y cell damage, miR-183-5p functions crucially in mepivacaine-mediated cell damage. This study provides a theoretical basis for elucidating the mechanism of mepivacaine-induced nerve cell damage, and overexpressed miR-183-5p likely become a novel strategy to combat mepivacaine-induced nerve damage.Abbreviations:miRNA: Micro RNA; PDCD4: Programmed Cell Death 4; MDA: Malondialdehyde; SOD: Superoxide Dismutase; ROS: Reactive Oxygen Species; WT: Wild Type; Mut: Mutant; UTR: Untranslated Region; IL-6: Interleukin-6; IL-1ß: Interleukin-1ß; TNF-α: Tumor Necrosis Factor-α; IL-8: Interleukin-8; COX-2: Cyclooxygenase-2; iNOS: inducible NOS; MEP: Mepivacaine.

Desensitisation of the distal forelimb following intrathecal anaesthesia of the carpal sheath in horses.

BACKGROUND: The effect of intrathecal anaesthesia of the carpal sheath on distal forelimb sensitivity in horses remains unknown. OBJECTIVES: To assess the effect of carpal sheath anaesthesia on skin sensitivity of the distal forelimb and to determine potential locations for desensitisation of palmar nerves. STUDY DESIGN: In vivo experimental and descriptive anatomical studies. METHODS: Mepivacaine hydrochloride 2% (0.6 mg/kg) was injected unilaterally in the carpal sheath of 8 horses. Mechanical nociception of the distal forelimb was measured with a dynamometer and compared with the control limb at t0, t15, t30, t60, t90, t120 and t180 minutes . Additionally, the carpal sheath of 10 pairs of cadaveric limbs was injected with latex and potential locations for anaesthetic diffusion to the neighbouring nerves were identified during longitudinal dissection (one limb) and in 3-cm-thick transverse cuts (opposite limb). RESULTS: Six of 8 horses (75%) were completely desensitised at the level of both heel bulbs. Anaesthetic injection was not smooth in the 2 horses without desensitisation. Desensitisation started between 30 and 60 minutes in 67% of desensitised heel bulbs (8/12), and 50% (6/12) of them were still completely desensitised at 180 minutes. Cadaveric specimens revealed close proximity between the sheath and the medial palmar nerve as it travels inside the mesotenon of the digital flexor tendons in the carpal region and with both palmar nerves at the proximal metacarpal region. MAIN LIMITATIONS: Skin mechanical nociception does not necessarily correlate with deep pain but remains the main clinical tool used by practitioners to assess distal limb anaesthesia. CONCLUSIONS: Intrathecal anaesthesia of the carpal sheath led to distal limb skin desensitisation through diffusion to the palmar nerves at 2 possible locations. Carpal sheath anaesthesia should be interpreted within 15 minutes following injection and anaesthetic blocks distal to the carpus should be delayed for more than 3 hours following carpal sheath anaesthesia.

The effect of intra-articular mepivacaine administration prior to carpal arthroscopy on anesthesia management and recovery characteristics in horses.

OBJECTIVE: To evaluate the effects of intra-articular (IA) mepivacaine administration prior to carpal arthroscopy on anesthetic drug requirements, blood pressure support, hemodynamic variables, and quality of recovery in horses. STUDY DESIGN: Experimental, analytical, cohort study. SAMPLE POPULATION: Twenty-two horses (n = 11 horses/group). METHODS: Horses were anesthetized by using the same protocol, but an IA injection of mepivacaine or saline was performed before carpal arthroscopy. End-tidal isoflurane concentration, heart rate, and mean arterial pressure were recorded at specific time points. Quality of recovery was scored by the anesthetist, who was unaware of group assignment. Data were analyzed by using two-way repeated-measures analysis of variance. RESULTS: Mean arterial pressure was higher during joint distension in the control group compared with baseline (7% higher, P = .02) and with the treatment group (10% higher, P = .04). Heart rate was higher in the control group compared with the treatment group during joint distension (8% higher, P = .04) and chip removal (11% higher, P = .03). Heart rate was higher in the control group compared with baseline during chip removal (5.5% higher, P = .04). Two horses in the control group required additional ketamine vs none in the treatment group. Quality of recovery was not different between groups. CONCLUSION: Intra-articular mepivacaine resulted in fewer detectable reactions to surgical stimulation, with similar recovery scores and blood pressure support requirements. CLINICAL SIGNIFICANCE: Intra-articular anesthesia prior to arthroscopy can be used safely in the horse and should be considered as a part of balanced anesthetic protocols.

Comparison of speed of onset and analgesic effect of 2% mepivacaine hydrochloride deposited within or outside the neurovascular bundle at the level of the proximal sesamoid bones in horses with naturally occurring forefoot-related lameness.

OBJECTIVE: To compare the speed of onset and analgesic effect of mepivacaine deposited within or immediately outside the neurovascular bundle at the base of the proximal sesamoid bones in horses. ANIMALS: 6 horses with naturally occurring forefoot-related lameness. PROCEDURES: In a crossover study design, horses were randomly assigned to receive 1 of 2 treatments first, with the second treatment administered 3 to 7 days later. Trotting gait was analyzed with an inertial sensor-based motion analysis system immediately before treatment to determine degree of lameness. Afterward, ultrasound guidance was used to inject 2% mepivacaine hydrochloride around the palmar digital nerves of the affected forelimb at the level of the base of the proximal sesamoid bones either within the subcircumneural space or outside the circumneural sheath. After injection, gait was reevaluated at 5-minute intervals for 45 minutes. RESULTS: Mepivacaine deposition outside the circumneural sheath did not resolve lameness in any horse; for 3 horses, the mean time to 70% reduction of initial vertical head movement was 13.3 minutes, and the remaining 3 horses had no such reduction at any point. Mepivacaine deposition within the subcircumneural space resulted in a mean time to 70% reduction of initial vertical head movement of 6.7 minutes and mean time to resolution of lameness of 21.7 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that when peripheral nerves of horses lie within a sheath, local anesthetic solution should be deposited within the sheath for an effective nerve block. If local anesthetic solution is deposited outside the sheath, the nerve block may yield erroneous results.

Mepivacaine reduces calcium transients in isolated murine ventricular cardiomyocytes.

BACKGROUND: The potential mechanism of mepivacaine's myocardial depressant effect observed in papillary muscle has not yet been investigated at cellular level. Therefore, we evaluated mepivacaine's effects on Ca2+ transient in isolated adult mouse cardiomyocytes. METHODS: Single ventricular myocytes were enzymatically isolated from wild-type C57Bl/6 mice and loaded with 10 µM fluorescent Ca2+ indicator Fluo-4-AM to record intracellular Ca2+ transients upon electrical stimulation. The mepivacaine effects at half-maximal inhibitory concentration (IC50) was determined on calibrated cardiomyocytes' Ca2+ transients by non-parametric statistical analyses on biophysical parameters. Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2 were used to test a possible mechanism to explain mepivacaine-induced Ca2+ transients' reduction. RESULTS: A significant inhibition at mepivacaine's IC50 (50 µM) on Ca2+ transients was measured in biophysical parameters such as peak (control: 528.6 ± 73.61 nM vs mepivacaine: 130.9 ± 15.63 nM; p < 0.05), peak area (control: 401.7 ± 63.09 nM*s vs mepivacaine: 72.14 ± 10.46 nM*s; p < 0.05), slope (control: 7699 ± 1110 nM/s vs mepivacaine: 1686 ± 226.6 nM/s; p < 0.05), time to peak (control: 107.9 ± 8.967 ms vs mepivacaine: 83.61 ± 7.650 ms; p < 0.05) and D50 (control: 457.1 ± 47.16 ms vs mepivacaine: 284.5 ± 22.71 ms; p < 0.05). Combination of mepivacaine with NCX blockers ORM-10103 or NiCl2 showed a significant increase in the baseline of [Ca2+] and arrhythmic activity upon electrical stimulation. CONCLUSION: At cellular level, mepivacaine blocks Na+ channels, enhancing the reverse mode activity of NCX, leading to a significant reduction of Ca2+ transients. These results suggest a new mechanism for the mepivacaine-reduction contractility effect.

Effect of 3% chloroprocaine hydrochloride when used for median and ulnar regional nerve blocks in lame horses.

OBJECTIVE: To assess onset of analgesia for 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when used for median and ulnar nerve blocks in lame horses. ANIMALS: 6 naturally lame horses. PROCEDURES: A crossover experiment was conducted. Horses were assigned to 1 of 2 treatment groups (3% chloroprocaine or 2% mepivacaine first). Median and ulnar nerve blocks were performed in the lame limb with the assigned treatment. Lameness was objectively evaluated before treatment administration and at various points for 120 minutes after treatment with a wireless inertial sensor-based motion analysis system. Following a 7-day washout period, horses then received the other treatment and lameness evaluations were repeated. RESULTS: Median and ulnar nerve blocks performed with 3% chloroprocaine resulted in more consistent, rapid, and profound amelioration of lameness than did blocks performed with 2% mepivacaine. Lameness decreased more between 20 and 40 minutes after injection when 3% chloroprocaine was used than when 2% mepivacaine was used. Complete resolution of lameness was detected a mean of 9 minutes after injection when median and ulnar nerve blocks were performed with 3% chloroprocaine and a mean of 28 minutes after injection when performed with 2% mepivacaine. CONCLUSIONS AND CLINICAL RELEVANCE: 3% chloroprocaine had a more rapid onset and provided better analgesia for median and ulnar nerve blocks in horses with naturally occurring lameness, compared with 2% mepivacaine. These favorable properties suggest that 3% chloroprocaine would be useful for performance of median and ulnar regional nerve blocks during complicated lameness evaluations.

Prospective randomized investigation of topical anesthesia during unilateral laparoscopic ovariectomy in horses.

OBJECTIVE: To compare pain-related responses in mares receiving topical or injected anesthesia of the ovarian pedicle prior to standing unilateral laparoscopic ovariectomy. STUDY DESIGN: Prospective randomized, blinded, placebo-controlled study. ANIMALS: Fifteen healthy research mares. METHODS: Mares were restrained in stocks and administered sedation. A right or left paralumbar ovariectomy was performed by using a laparoscopic portal and two instrument portals. Mares were divided into two treatment groups, and equal volumes of mepivacaine anesthesia were administered either topically (n = 8) or by injection into the ovarian pedicle (n = 7). Saline controls were simultaneously administered topically (n = 7) or by injection (n = 8), and surgeons were blinded to the treatment group. Ovarian removal was performed with traumatic forceps and a blunt tip vessel sealer and divider. Pain responses were measured by operative visual analog scale (VAS) scoring and perioperative serum cortisol response. Visual analog scale and serum cortisol were compared between groups by using Mann-Whitney testing. Serum cortisol concentrations were evaluated using repeated-measures one-way analysis of variance. RESULTS: Ovaries were removed in all mares by using the described technique without operative complications. Quantity of sedation required to complete the procedure, operative VAS scores, and perioperative cortisol concentrations did not differ between treatment groups. CONCLUSION: Application of topical mepivacaine to the ovary provided intraoperative analgesia similar to injection of the ovarian pedicle when performing unilateral standing laparoscopic ovariectomy in mares. CLINICAL SIGNIFICANCE: Topical anesthesia application to the ovary could provide an alternative to laparoscopic needle use, reducing the risk of inadvertent trauma to the pedicle or other visceral organs during laparoscopic ovariectomy.

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.

Buffering mepivacaine with sodium bicarbonate speeds and potentiates analgesia of median and ulnar nerve blocks performed on horses.

The objective of this study was to determine if buffering mepivacaine HCL (mepHCl) with sodium bicarbonate (NaHCO3) would significantly decrease the time to onset of analgesia when performing median and ulnar nerve blocks in naturally lame horses. Median and ulnar nerve blocks were performed on the naturally lame limb of nine horses during two separate study periods, with a minimum washout period of three days between study periods. Nerve blocks were performed by administering mepHCl alone or mepHCl mixed with NaHCO3 (nine parts 2 per cent mepHCl to one part 8.4 per cent NaHCO3). Lameness was evaluated objectively using a wireless, inertial, sensor-based, motion analysis system (Lameness Locator) prior to the high regional nerve block and every five minutes following administration of the nerve block for 75 min. Resolution of lameness occurred earlier and was more profound for horses administered median and ulnar nerve blocks performed with mepHCl and NaHCO3 than when these nerve blocks were performed using only mepHCl.

Impact of dexmedetomidine on the tissue distribution, anesthetic action, and hemodynamic effects of mepivacaine.

The present study investigated the regional blood flow, tissue distribution, local anesthetic action, and hemodynamic effects of mepivacaine containing dexmedetomidine hydrochloride (DEX) in rats. Blood flow was measured after injection of 0.5% mepivacaine (M group), 12.5 µg/ml DEX (D group), or 0.5% mepivacaine containing 12.5 µg/ml DEX (DM group) into the upper lip. Mepivacaine distribution was autoradiographically observed in maxillary bone resected after injection of 0.5% 3H-mepivacaine (HM group) or 0.5% 3H-mepivacaine containing 12.5 µg/ml DEX (DHM group) into the palatal mucosa adjacent to the right maxillary first molar. Radioactivity was also measured using a liquid scintillation counter. SEP were measured to analyze anesthetic action. Blood pressure and heart rate were measured to compare hemodynamic effect. The addition of DEX significantly decreased blood flow compared to M group from 10 to 60 min after injection. The addition of DEX significantly increased the amount of radioactivity compared to HM group in the palatal mucosa from 5 to 60 min after injection and in the body of the maxilla from 2 to 60 min after injection. Maximum blood radioactivity was measured at 5 min after injection in HM group and 50 min after injection in DHM group. The addition of DEX significantly decreased peak-to-peak amplitudes compared to M group until 60 min after injection. No significant hemodynamic differences were observed. DEX enhances the action of mepivacaine in reducing regional blood flow prolongs its tissue retention, and increases the local anesthetic action without affecting hemodynamics on local administration.

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.

OBJECTIVE: 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. METHODS: Our goal is to detect women who complain of sexual disfunction and perineal pain 2 and 6 months 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% (8 ml) and betamethasone acetate (2 ml). RESULTS: Twenty-seven women were treated with vaginal injections directly into the trigger points. Seven of them [7/27 (25.92%)] were treated 2 months after delivery and experienced complete recovery of their perineal pain 4 months after the treatment. Those who first chose conservative treatment [20/27 (74.08%)] were also assessed 6 months 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. CONCLUSION: 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.

OBJECTIVES: 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. METHODS: 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. KEY FINDINGS: 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. CONCLUSIONS: Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective action over motor block has a better potency than mepivacaine or doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.