Coadministration Of Lidocaine Research Articles

Effects of meloxicam on the welfare of Holstein calves from 6 weeks to 6 months old undergoing amputation dehorning

Amputation dehorning (AD) is a common practice performed on calves, causing harmful effects such as pain, distress, anxiety, and fear. These effects extend to behavioral, physiological, and hematological responses, prompting serious ethical concerns regarding animal welfare, even when performed with local anesthesia. Meloxicam, a nonsteroidal anti-inflammatory drug, has been widely used to mitigate the side effects of dehorning and disbudding in calves. However, there is a notable gap in research regarding the effects of meloxicam on calves aged 6 wk to 6 mo undergoing AD procedures. This study was designed to assess the effectiveness of co-administering meloxicam with lidocaine, a cornual nerve anesthetic, in alleviating the adverse effects caused by the AD procedure in calves within this age range, compared with the use of lidocaine alone. Thirty Holstein calves were enrolled and randomly divided into 2 groups. The first group received a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 0.9% saline at a dose of 0.025 mL/kg in the neck, administered 10 min before the AD procedure. The second group received a combination of lidocaine and meloxicam: a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 20 mg/mL meloxicam at a dose of 0.025 mL/kg in the neck, also administered 10 min before the AD procedure. To avoid subjective bias, the researchers were blinded to the treatment groups. Pain-related behaviors, including tail flicking, head shaking, ear flicking, head rubbing, head crossing bar, and kicking, were observed, and physiological parameters, including heart rate, rectal temperature, respiration rate, mechanical nociceptive threshold (MNT), daily active steps, and food intake were monitored. Hematological conditions were determined using enzyme-linked immunosorbent assays and routine blood tests. The data were processed using a generalized linear mixed model. The outcomes demonstrated that the AD procedure increased the frequencies of ear flicking and resulted in rises in the respiration rate, heart rate, rectal temperature, and daily active steps. It also led to decreases in total food intake, forage intake, hay intake, MNT, and increased concentrations of prostaglandin E2 (PgE2), IL-1β, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and malondialdehyde, as well as glutathione peroxidase activity. However, calves that received meloxicam treatment showed significant improvements in response to the AD procedure, including lower respiration rates, heart rates, and rectal temperatures; higher MNT; and lower intermediate cell ratio. They also had higher red blood counts, hemoglobin levels, hematocrit values; larger mean platelet volumes; and lower concentrations of PgE2, IL-1β, TNF-α, and NO. These results suggest that co-administration of lidocaine and meloxicam may aid in mitigating the adverse effects induced by the AD procedure on these calves, thereby supporting the use of meloxicam in conjunction with a local anesthetic in AD procedures for calves aged 6 wk to 6 mo.

A Clinical Trial on the Welfare Effects of Administering Meloxicam to 10-21 Day Dairy Calves Following Caustic Paste Disbudding.

Caustic paste disbudding (CPD) is widely utilized for calves, which has been known to result in adverse effects on the calves and ethical concerns related to animal welfare, despite the use of local anesthetics. The administration of meloxicam has been demonstrated to provide benefits in alleviating pain and inflammation in juvenile calves under nine days old and subjected to CPD. Nonetheless, there is a scarcity of literature documenting the beneficial impact of meloxicam in alleviating pain in calves aged over nine days that have undergone CPD. Therefore, the objective of this clinical trial was to evaluate the efficacy of administering meloxicam and lidocaine for cornual nerve block together in mitigating the deleterious effects of CPD, as opposed to using lidocaine alone in calves older than nine days. Thirty Holstein calves, aged between 10 and 21 days, were enrolled and randomly assigned to 1 of 2 treatments: lidocaine alone (Placebo), lidocaine and normal saline treatment before CPD, and lidocaine plus meloxicam (MX), lidocaine and 0.5mg/kg of meloxicam treatment prior to CPD. The researchers were blind to the treatment of calves to control the subjective error. The occurrences of actions associated with pain, which included head shaking, head rubbing, ear flicking, tail flicking, kicking, and head passing through the fence, were recorded. Physiological performance, including the respiration rate, heart rate, rectal temperature, mechanical nociceptive threshold (MNT), food intake, and daily activity level, was monitored. Hematological conditions were ascertained through the use of routine blood tests and enzyme-linked immunosorbent assay. The generalized linear mixed model (GLMM) was employed to analyze the data. The research findings revealed that applying the CPD procedure significantly elevated the frequencies of tail flicking, head shaking, and kicking, resulted in increases in respiratory rate, heart rate, daily active steps, and food intake and a decrease in MNT, and led to alterations in hematological markers, including platelet counts, mean platelet volume, prostaglandin E2, constitutive nitric oxide synthase, and hydroxyl radical. Considerable benefits, such as lower heart rates, higher food intake, and MNTs, as well as lower levels of white blood cell counts, lymphocyte counts, hemoglobin, mean platelet volume, prostaglandin E2, tumor necrosis factor-α, constitutive nitric oxide synthase, malondialdehyde, and hydroxyl radical, were observed in the calves that received meloxicam treatment in response to CPD. The findings of the study indicate that the co-administration of lidocaine and meloxicam provides obvious benefits in mitigating pain, inflammation, and oxidative stress in calves aged over nine days and undergoing CPD. This endorses the use of meloxicam during the disbudding and dehorning procedures of calves.

Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats.

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014)μmol] > oxymetazoline [0.25 (0.22-0.28) μmol] > naphazoline [0.42 (0.34-0.53)μmol] = bupivacaine [0.43 (0.37-0.50) μmol] > xylometazoline [1.34 (1.25-1.45)μmol] > lidocaine [5.86 (5.11-6.72) μmol] > tetrahydrozoline [6.76 (6.21-7.36)μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75 ). Co-administration of lidocaine (ED50 ) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Cardiotoxicity of Consolida rugulosa, a poisonous weed in Western China

Poisonous weeds are a global problem since they not only hinder local economic development, but also cause ecological harm. Consolida rugulosa (family Ranunculaceae) is a weed that is widespread in Northwestern China and causes severe poisoning when ingested by livestock. In the present study, we purified the toxins in this plant and investigated their mechanism of action. Five natural diterpene alkaloids (compounds 1–5)—including two new compounds (1 and 2)—were isolated, and five semi-synthetic derivatives (6–10) were synthesised based on 4 or 5 for structure-activity analysis. The toxicity of the compounds was evaluated in vitro with lactate dehydrogenase (LDH) assay. All of the compounds—especially 1—stimulated LDH release in primary cultured rat myocardial cells, an effect that was blocked by the Na+ channel blocker lidocaine. Electrocardiography revealed that rats treated with 1 had severe arrhythmia, while heart Doppler echocardiography and analysis of serum biomarkers levels revealed that administration of 1 for 15 days induced changes in cardiac structure and myocardial enzyme levels. These effects were antagonised by lidocaine treatment. Thus, diterpene alkaloids are the main compounds responsible for the cardiotoxicity of C. rugulosa, which can be mitigated by co-administration of lidocaine.

Naloxone prolongs cutaneous nociceptive block by lidocaine in rats.

We aimed to investigate the local anesthetic properties of naloxone alone or as an adjunct for the local anesthetic lidocaine. After the block of the cutaneous trunci muscle reflex (CTMR) with drugsdelivery by subcutaneous infiltration, cutaneous nociceptive block was tested on the ratsꞌ backs. We demonstrated that naloxone, as well as lidocaine, elicited cutaneous analgesia dose-dependently. The relative potency in inducing cutaneous analgesia was lidocaine [22.6 (20.1 - 25.4) μmol/kg] > naloxone [43.2 (40.3 - 46.4) μmol/kg] (P<0.05). On an equianesthetic basis [50% effective dose (ED50 ), ED25 , and ED75 ], naloxone displayed a greater duration of cutaneous analgesic action than lidocaine (P<0.01). Coadministration of lidocaine (ED95 or ED50 ) and ineffective-dose naloxone (13.3μmol/kg) intensifies sensory block (P<0.01) with prolonged duration of action (P<0.001) compared with lidocaine (ED95 or ED50 ) alone or naloxone (13.3μmol/kg) alone on infiltrative cutaneous analgesia. The preclinical data showed that naloxone is less potent than lidocaine as an infiltrative anesthetic, but its analgesic duration was longer than that of lidocaine. Furthermore, naloxone prolongs lidocaine analgesia, acting synergistically for nociceptive block.

Possible utility of contrast-enhanced ultrasonography for detecting spread of local anesthetic in nerve block.

This study demonstrated the effects of perfluorobutane (Sonazoid®) with contrast-enhanced ultrasonography (CEUS) to identify the spread of local anesthetics in ultrasound-guided nerve block. This study consists of simulation, cadaveric, and animal studies. In a simulation study, 1% lidocaine with 10- to 1000-fold diluted Sonazoid®, a US-specific contrast agent to diagnose hepatic and breast cancers (0.5mL), was injected into a resin-based phantom to determine the optimal concentration for ultrasound-guided peripheral nerve block. The enhanced area was measured by direct observation and ultrasonography (US). In the cadaver study, ultrasound-guided sciatic nerve block was performed at the popliteal fossa in the 9 extremities, and 5mL of the optimally diluted Sonazoid® defined in the simulation study with X-ray contrast medium and blue dye was injected. Longitudinal spread of the solution was measured by CEUS, X-ray imaging and anatomical dissection. In the animal study, the optimally diluted Sonazoid® was injected around the sciatic nerve of rats (n=6), and neuronal function and toxicity were evaluated by behavioral and histological estimation. The simulation study proved that 100-fold diluted Sonazoid® was the optimal concentration. In the cadaver study, CEUS and anatomical dissection (r=0.90, P=0.0020) or radiography (r=0.84, P=0.0072) showed high agreement and correlation with the longitudinal spread. CEUS clearly showed a fine intraneuronal injection image compared to the usual B-mode imaging. The animal study suggested no adverse effects by co-administration of lidocaine and Sonazoid®. CEUS with 100-fold diluted Sonazoid® could identify the spread of local anesthetic as well as radiography and anatomical dissection, and distinguish between intra- and extraneuronal injections without neurodegeneration.

Caudal epidural analgesia using lidocaine alone or in combination with ketamine in dromedary camels Camelus dromedarius.

This study was performed to investigate the analgesic effect of lidocaine and a combination of lidocaine and ketamine following epidural administration in dromedary camels. Ten 12-18-month-old camels were randomly divided into two equal groups. In group L, the animals received 2% lidocaine (0.22 mg/kg) and in group LK the animals received a mixture of 10% ketamine (1 mg/kg) and 2% lidocaine (0.22 mg/kg) administered into the first intercoccygeal (Co1-Co2) epidural space while standing. Onset time and duration of caudal analgesia, sedation level and ataxia were recorded after drug administration. Data were analysed by U Mann-Whitney tests and significance was taken as p &lt; 0.05. The results showed that epidural lidocaine and co-administration of lidocaine and ketamine produced complete analgesia in the tail, anus and perineum. Epidural administration of the lidocaine-ketamine mixture resulted in mild to moderate sedation, whilst the animals that received epidural lidocaine alone were alert and nervous during the study. Ataxia was observed in all test subjects and was slightly more severe in camels that received the lidocaine-ketamine mixture. It was concluded that epidural administration of lidocaine plus ketamine resulted in longer caudal analgesia in standing conscious dromedary camels compared with the effect of administering lidocaine alone.

Propranolol elicits cutaneous analgesia against skin nociceptive stimuli in rats

The purpose of this study was to investigate the cutaneous analgesic effect of propranolol and compare with a local anesthetic lidocaine. The potencies and equipotent doses were determined for infiltrative cutaneous analgesia on the rat back by determination of dose–response curves for propranolol and lidocaine. Propranolol as well as lidocaine elicited dose–dependent cutaneous analgesia. On a 50% effective dose (ED50) basis, the relative potency was propranolol (10.3 [8.9–11.9]μmolkg−1)>lidocaine (25.8 [24.3–27.8]μmolkg−1) (P<0.01). On equianalgesic doses (ED25, ED50, ED75), propranolol produced longer action of infiltrative cutaneous analgesia than lidocaine (P<0.01). Coadministration of lidocaine (25.8μmolkg−1) and propranolol (1.7μmolkg−1) exhibited greater blockade and duration than lidocaine (25.8μmolkg−1) or propranolol (1.7μmolkg−1) alone. Propranolol displayed more potent and longer duration of action than lidocaine at producing cutaneous analgesia. Furthermore, propranolol may prove useful as an adjuvant for lidocaine in producing cutaneous analgesia.

Evaluation of Nociception, Sedation, and Cardiorespiratory Effects of a Constant Rate Infusion of Xylazine Alone or in Combination with Lidocaine in Horses

This study aimed to evaluate the effects of a constant rate infusion (CRI) of xylazine or xylazine in combination with lidocaine on nociception, sedation, and physiologic values in horses. Six horses were given intravenous (IV) administration of a loading dose (LD) of 0.55 mg/kg of xylazine followed by a CRI of 1.1 mg/kg/hr. The horses were randomly assigned to receive three treatments, on different occasions, administered 10 minutes after initiation of the xylazine CRI, as follows: control, physiologic saline; lidocaine low CRI (LLCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.025 mg/kg/min); and lidocaine high CRI (LHCRI), lidocaine (LD: 1.3 mg/kg, CRI: 0.05 mg/kg/min). A blinded observer assessed objective and subjective data for 50 minutes during the CRIs. In all treatments, heart and respiratory rates decreased, end-tidal carbon dioxide concentration increased, and moderate to intense sedation was observed, but no significant treatment effect was detected in these variables. Ataxia was significantly higher in LHCRI than in the control treatment at 20 minutes of infusion. Compared with baseline values, nociceptive threshold increased to as much as 79% in the control, 190% in LLCRI, and 158% in LHCRI. Nociceptive threshold was significantly higher in LLCRI (at 10 and 50 minutes) and in LHCRI (at 30 minutes) than in the control treatment. The combination of CRIs of lidocaine with xylazine produced greater increases in nociceptive threshold compared with xylazine alone. The effects of xylazine on sedation and cardiorespiratory variables were not enhanced by the coadministration of lidocaine. The potential to increase ataxia may contraindicate the clinical use of LHCRI, in combination with xylazine, in standing horses.

Lidocaine for prolonged and intensified spinal anesthesia by coadministration of propranolol in the rat

Although the coadministration of lidocaine with propranolol interferes with the metabolic profile (pharmacokinetics), its pharmacodynamics is still unclear. In this report, we investigate whether propranolol can potentiate the effect of lidocaine. Rats received spinal anesthesia with lidocaine co-injected with propranolol. After intrathecal injections of drugs in rats, three neurobehavioral examinations (motor function, proprioception, and nociception) were performed. We showed that lidocaine and propranolol elicited a spinal blockade in motor function, proprioception, and nociception. Propranolol at the dose of 0.82μmol/kg produced no spinal anesthesia. Co-administration of lidocaine [50% effective dose (ED50) or ED95] and propranolol (0.82μmol/kg) produced greater spinal anesthesia than lidocaine (ED50 or ED95), respectively. These preclinical findings demonstrated that propranolol and lidocaine displayed spinal anesthesia. When combined with propranolol, lidocaine elicited a supra-additive effect of spinal anesthesia.

Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses

To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine. 24 horses. Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations. Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E(2) metabolite and thromboxane B(2) concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively. In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E(2) metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.

In vitro binding of lidocaine to liver tissue under the influence of propranolol: Another mechanism of interaction?

The co-administration of lidocaine and propranolol leads to significant drug-drug interactions. Beta-blockers decrease liver perfusion and inhibit the activity of hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily. Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and an increase in its serum concentrations. In this study the ability of propranolol to displace lidocaine from its binding sites in liver tissue has been examined through an in vitro model. Rat liver slices were incubated together with propranolol and/or lidocaine in human serum and the percentage of the bound fraction of lidocaine in the experimental mixture was assessed. The present results indicate that propranolol significantly decreases the binding process of lidocaine in liver tissue. This effect develops only when blood is used as incubation medium and the incubation period lasts 60 min. In conclusion, propranolol can displace lidocaine from liver proteins and therefore the co-administration of the two drugs may increase the free fraction of lidocaine excreted by the liver. However, this result arises from an in virro model and thus further investigation is needed.

Down-regulation of norepinephrine transporter expression on membrane surface induced by chronic administration of desipramine and the antagonism by co-administration of local anesthetics in mice

We have previously shown that chronic administration of the antidepressant desipramine, a norepinephrine transporter (NET) inhibitor to mice markedly enhanced convulsions induced by local anesthetics and that behavioral sensitization may be relevant to decreased [ 3H]norepinephrine uptake by the isolated hippocampus. The co-administration of local anesthetics with desipramine reversed the behavioral sensitization and down-regulation of NET function induced by desipramine. The present study aimed to elucidate whether chronic treatment with desipramine regulates the expression of NET protein examined in membrane fractions in various brain regions and whether co-administration of local anesthetics affects the desipramine-induced alteration of NET expression. Desipramine with or without local anesthetics was injected intraperitoneally once a day for 5 days. The animals were decapitated 48 h after the last administration of drugs and the whole cell fraction, membrane fraction and cell-surface protein fraction were prepared. [ 3H]nisoxetine binding was significantly reduced in the P2 fraction of the hippocampus by chronic administration of desipramine, and the reduction was overcome by co-administration of lidocaine with desipramine. Immunoreactive NET was detected by SDS-PAGE and immunoblotting in the murine hippocampus. NET protein expression in the whole cell fraction and membrane fraction was not affected by treatment with any drugs. However, administration of desipramine significantly reduced the amount of immunoreactive NET in the cell-surface protein fraction. This reduction was blocked by simultaneous injection of lidocaine, bupivacaine or tricaine. These results indicate that the NET down-regulation indicated by the reduction of [ 3H]nisoxetine binding was induced by administration of desipramine via decrease of NET localization on the cell surface. The antagonistic actions of local anesthetics against NET down-regulation by desipramine were related to alterations of the cell-surface localization of NET.

Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics

Alterations of norepinephrine transporter (NET) function by chronic inhibition of NET in relation to sensitization to seizures induce by cocaine and local anesthetics were studied in mice . Daily administration of desipramine, an inhibitor of the NET, for 5 days decreased [ 3H]norepinephrine uptake in the P2 fractions of hippocampus but not cortex, striatum or amygdalae. Co-administration of lidocaine, bupivacaine or tricaine with desipramine reversed this effect. Daily treatment of cocaine increased [ 3H]norepinephrine uptake into the hippocampus. Daily administration of desipramine increased the incidence of appearance of lidocaine-induced convulsions and decreased that of cocaine-induced convulsions. Co-administration of lidocaine with desipramine reversed the changes of convulsive activity of lidocaine and cocaine induced by repeated administration of desipramine. These results suggest that down-regulation of hippocampal NET induced by chronic administration of desipramine may be relevant to desipramine-induced sensitization of lidocaine convulsions. Inhibition of Na + channels by local anesthetics may regulate desipramine-induced down-regulation of NET function. Repeated administration of cocaine induces up-regulation of hippocampal NET function. Desipramine-induced sensitization of lidocaine seizures may have a mechanism distinct from kindling resulting from repeated administration of cocaine.

Effects of propranolol or paracetamol on lidocaine concentrations in serum and tissues

Purpose: The goal of this study was to determine the interaction of lidocaine after paracetamol or propranolol administration. Materials and Methods: Group A rats received a mixture of cold lidocaine and 14C lidocaine into the masseter muscle. Group B rats received lidocaine and paracetamol 7.5 mg/kg orally, whereas group C received lidocaine intramuscularly and propranolol 1.5 mg/kg orally. Five consecutive doses were administered. The levels of these drugs were estimated in serum and the total concentration and the percent protein binding of lidocaine in tissues (liver and mandible) were determined. The rats were killed 2 hours after the last dose. Results: The results suggest that lidocaine concentrations in serum were significantly increased after either paracetamol or propranolol administration. Additionally, the combined therapy of propranolol and lidocaine resulted in a significant decrease in the total concentration and the percent protein binding of lidocaine in tissues. Conclusions: The coadministration of lidocaine with paracetamol or propranolol interferes with the metabolic profile, resulting in pharmacokinetic interactions that may be significant for the determination of the correct dose of lidocaine in clinical applications. © 2003 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofacial Surg 61:604-607, 2003

A dissociative change in the efficacy of supraspinal versus spinal morphine in the neuropathic rat

The efficacy of spinally versus supraspinally administered morphine was studied in rats with a spinal nerve ligation-induced neuropathy. Behavioural assessment indicated that the effect of intrathecally administered morphine on pain-related responses was attenuated when compared with unoperated controls. The decreased efficacy of spinal morphine was associated with neuropathic symptoms, since sham ligation or nerve ligation without accompanying tactile allodynia did not lead to spinal inefficacy of morphine. In contrast, the pain attenuating effect of morphine in the periaqueductal gray (PAG) was enhanced in neuropathic animals. The effect of systemically administered morphine on pain-related behavior of neuropathic rats was in the same range as in controls or decreased, depending on the test. Coadministration of lidocaine or MK-801, a N-methyl- d-aspartate (NMDA) receptor antagonist, into the rostroventromedial medulla enhanced the tactile antiallodynic but not the thermal antinociceptive effect of intrathecally administered morphine in neuropathic animals. Supraspinal administration of MK-801 or lidocaine did not influence efficacy of spinal morphine in sham-operated animals. Electrophysiological recordings of nociceptive wide-dynamic range (WDR) neurons in the deep spinal dorsal horn of pentobarbitone-anesthetized animals corresponded to a large extent with behavioral results. The inhibitory effect of spinally and systemically administered morphine on WDR neuron responses was attenuated whereas that induced by morphine in the PAG was enhanced in neuropathic animals. The results indicate that in spinal nerve ligation-induced neuropathy the efficacy of spinal morphine is decreased whereas that of supraspinal morphine is increased. Descending influence from brainstem-spinal pathways, involving NMDA receptors in the rostroventromedial medulla, may contribute to the selective reduction in tactile antiallodynic efficacy of spinal morphine.

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination spinal analgesic chemotherapy: a systematic review.

Combination spinal analgesic chemotherapy: a systematic review.

Prefrontal cortical manipulations alter the effects of intra-ventral striatal dopamine antagonists on fixed-interval performance in the rat

The nature of the functional relationships between areas of prefrontal cortex and ventral striatum remain undefined. This study was designed to examine functional interactions between activity in two areas of prefrontal cortex, the prelimbic (PL) and agranular insular (AI) areas, and ventral striatal (VS) dopamine (DA) function. Interactions were assessed using a Fixed Interval (FI) schedule of reinforcement shown previously in our laboratory to be modulated by VS DA function. The study compared changes in FI performance following intra-VS DA antagonist injections alone (SCH23390+eticlopride) to those observed when either saline or saline+lidocaine were injected into prefrontal cortex after the intra-VS DA antagonist injections. The intra-VS DA antagonists alone decreased FI response rates and increased postreinforcement pause times at both dose combinations (1/0.1 and 3/0.3 μg of SCH23390/eticlopride per side). Neither saline nor saline+lidocaine injected into the PL area of prefrontal cortex altered the effects of intra-VS DA antagonists on FI performance. Saline administration into the AI area of prefrontal cortex, however, eliminated the FI rate-decreasing effects of intra-VS DA antagonists. The agent or mechanism of this effect, whether it be saline, the act of inserting the cannulae into the cortical tissue, or the act of injecting fluid into this tissue, is not clear. This effect of AI saline was prevented by coadministration of lidocaine with saline into AI. These results, coupled with those from a previous experiment examining lesion effects in PL and AI on FI performance (Evans SB, Cory-Slechta DA. The effects of temporary lesions of the insular and medial prefrontal cortex on fixed-interval schedule-controlled behavior in the rat, Soc Neurosci Abstr 1996;22(1):159) suggest that PL might exert a tonic influence on VS DA function, since FI response rates gradually increase over a 2-week period following lesions of PL. In contrast, AI, although not normally modulating FI performance, can apparently influence VS DA function, possibly when alterations in activity are invoked in AI.

The Intraarticular and Periarticular Use of Corticosteroids in Knee and Shoulder

The use of corticosteroids in and around joints is warranted in a variety of clinical situations. The technique itself is well suited to office practice, is readily learned, and thus falls well within the domain of the family physician. The indications, contraindications, and potential complications of intraarticular steroids are reviewed, and the actual mechanics of injecting the knee and shoulder are presented. The coadministration of lidocaine can provide immediate relief and may also be of diagnostic use.