Local Anesthetic Agent Lidocaine Research Articles

The impact of Lidocaine gel on TNF-α expression in surgically induced oral mucosal ulcers: an immunohistochemical analysis in rabbits

Background: Besides being a local anesthetic agent lidocaine is a promising anti-inflammatory agent with limited studies on its effect on the mucosa. Aim: Assess the anti-inflammatory effect of lidocaine following surgical induction wound in the oral mucosa as assessed by tumor necrosis factor-α (TNF-α) expression. Materials and methods: The study was conducted on 32 albino rabbits that were categorized into 2 equal groups of 16 rabbits: In the control group an oral wound was surgically induced and left without treatment and in the treatment group an oral wound was surgically induced and received topical Lidocaine gel. Euthanasia of animals was carried out on days 1, 3, 7, and 10, and sample sites were processed for histopathological and immunohistochemical staining for TNF-α. Results: In the histological observations, it was noticed that the healing process was more rapid and convenient in the test group compared to the control group. For Immunohistochemical assessment, the TNF-α started to express clearly at 1 day and gradually decreased and disappeared at 10 days with a superior effect of the lidocaine group over the control group. Conclusion: Lidocaine seems to have anti-inflammatory reactions by lowering TNF-α levels and preventing the production of pro-inflammatory cytokines.

Efficacy of lidocaine versus mepivacaine in the management of myofascial pain

ObjectivesThere are many treatment modalities for myofascial pain, and recent findings reported in the literature highlight the superiority of using local anesthetics as the treatment of choice. The objective of the present study was to compare the effectiveness of two of the most used local anesthetic agents—lidocaine and mepivacaine—in the management of myofascial pain. Materials and methodsThirty patients (20 females, 10 males) were randomly assigned to one of two groups: 50% received lidocaine and 50% received mepivacaine. Trigger point injections in the orofacial region were administered 4 times, 10 days between each injection, with 4 weeks of follow-up after the end of the treatment course. Pain levels were recorded using a visual analog scale (VAS) at the time of follow-up and 30 min after injection. ResultsAll patients exhibited statistically significant improvement when comparing pre- and post-treatment mean values. Both local anesthetics (i.e., lidocaine and mepivacaine) were similarly effective for the management of myofascial pain (p = 0.875). The mepivacaine-treated group exhibited significantly lower post-injection tenderness than the lidocaine group (p = 0.038). There was no relationship between sex and treatment response. Female and male patients both reported similar responses in terms of VAS scores (p = 0.818). ConclusionNo drug was superior in the long term; thus, the clinician’s choice can be based on drug availability and patient medical history.

Formulation and Evaluation of Lidocaine Lipid Nanosystems for Dermal Delivery

The objective of the present investigation was to formulate solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for improving the dermal delivery of a local anesthetic agent lidocaine (LID). SLN and NLC were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction pattern (XRD), thermal behavior by differential scanning colorimeter (DSC) and surface morphology by transmission electron microscopy (TEM). LID-loaded SLN and NLC were formulated into hydrogels for topical application. The in vitro permeation profiles of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) were evaluated by using guinea pig skin. The in vivo efficacy of LID SLN gel, LID NLC gel, and a marketed LID formulation (Xylocaine gel) gel was evaluated on guinea pig using pinprick test. LID SLN showed a particle size of 78.1 nm with a polydispersity index of 0.556, whereas LID NLC showed a particle size of 72.8 nm with a polydispersity index of 0.463. The entrapment efficiency of LID in both SLN and NLC was 97% and 95.9%, respectively. The TEM studies revealed the almost spherical nature of LID SLN and NLC formulations. The XRD and DSC studies of LID SLN suggested amorphization of drug in the carrier system. The SLN formulation was stable with respect to particle size, polydispersity, and entrapment efficiency for 6 months at 40 degrees C/75% relative humidity (RH). Negligible leakage was observed for the NLC formulation when stored for 1 month at 40 degrees C/75% RH. In vitro permeation studies indicated that LID SLN gel and LID NLC gel significantly sustained the LID release compared to that of Xylocaine gel. The in vivo efficacy results supported the results of the in vitro permeation studies wherein the LID SLN gel and LID NLC gel resulted in fivefold and sixfold increase in duration of anesthesia, respectively, compared to that of Xylocaine gel.

Micellization and gelation in block copolymer systems containing local anesthetics

A formulation consisting of a eutectic mixture of lidocaine and prilocaine, Lutrol ® F68 and Lutrol ® F127, suitable for anesthetizing the periodontal pocket has previously been developed. This consists of discrete micelles with a diameter of 20–30 nm and has a suitable gelation temperature, a good release profile and excellent long-term stability. In this study, the unimer/micelle transition and gel formation of the formulation, in its concentrated state, are investigated using differential scanning calorimetry (DSC), dye solubilization, rheology, and nuclear magnetic resonance (NMR) self-diffusion. The critical micellization temperature (cmt) and gelation temperature are found to be interconnected and influenced by cosolutes, such as electrolytes and hydrophobic substances, the latter as found particularly for the eutectic mixture of the local anesthetic agents lidocaine and prilocaine. Both cmt and the gelation temperature decrease with increasing pH of the system, i.e. at reduced solubility of the active ingredients. Moreover, both cmt and the gelation temperature increase upon diluting the system with water. The ratio between the two block copolymers present in the system also has an impact on both cmt and the gelation temperature, resulting in a decrease in onset temperature of both processes with an increase of Lutrol ® F127. The amount of the active ingredients present in the micelle phase depends on the pH of the system being approximately 0% w/w at pH 5, 50–60% w/w at pH 7.8 and 80% w/w at pH 9.

Nonionic Cellulose Ethers as Potential Drug Delivery Systems for Periodontal Anesthesia

Nonionic cellulose ethers displaying a lower consolute temperature, or cloud-point, close to body temperature were investigated as potential carrier systems for the delivery of local anesthetic agents to the periodontal pocket. The interaction between the polymers, i.e., ethyl(hydroxyethyl)cellulose (EHEC) and hydrophobically modified EHEC (HM-EHEC), and ionic surfactants was determined in the absence and in the presence of the local anesthetic agents lidocaine and prilocaine. The cloud-point and rheology data indicate interactions between the polymer and both anionic and cationic surfactants. More precisely, a number of ionic surfactants were found to result in an increase in cloud-point at higher surfactant concentrations, a surfactant-concentration-dependent thickening, and a temperature-induced gelation upon heating. Upon addition of the local anesthetic agents lidocaine and prilocaine in their uncharged form to EHEC and HM-EHEC, in the absence of surfactants, only minor interaction with the polymer could be inferred. However, these substances were found to affect the polymer–surfactant interaction. In particular, the drug release rate in vitro as well as the stability and temperature-dependent viscosity were followed for an EHEC/SDS system and EHEC/myristoylcholine bromide system upon addition of lidocaine and prilocaine. The data indicate a possibility of formulating a local anesthetic drug delivery system suitable for administration into the periodontal pocket where at least small amounts of active ingredients can be incorporated into the system without severely affecting the gelation behavior. The results found for the cationic myristoylcholine bromide system are particularly interesting for the application in focus here since this surfactant is antibacterial and readily biodegradable.

Tonic blocking action of meperidine on Na+ and K+ channels in amphibian peripheral nerves.

Among opioids, meperidine (pethidine) also shows local anesthetic activity when applied locally to peripheral nerve fibers and has been used for this effect in the clinical setting for regional anesthesia. This study investigated the blocking effects of meperidine on different ion channels in peripheral nerves. Experiments were conducted using the outside-out configuration of the patch-clamp method applied to enzymatically prepared peripheral nerve fibers of Xenopus laevis. Half-maximal inhibiting concentrations were determined for Na+ channels and different K+ channels by nonlinear least-squares fitting of concentration-inhibition curves, assuming a one-to-one reaction. Externally applied meperidine reversibly blocked all investigated channels in a concentration-dependent manner, i.e., voltage-activated Na+ channel (half-maximal inhibiting concentration, 164 microM), delayed rectifier K+ channels (half-maximal inhibiting concentration, 194 microM), the calcium-activated K+ channel (half-maximal inhibiting concentration, 161 microM), and the voltage-independent flicker K+ channel (half-maximal inhibiting concentration, 139 microM). Maximal block in high concentrations of meperidine reached 83% for delayed rectifier K+ channels and 100% for all other channels. Meperidine blocks the Na+ channel in the same concentration range as the local anesthetic agent lidocaine (half-maximal inhibiting concentration, 172 microM) but did not compete for the same binding site as evaluated by competition experiments. Low concentrations of meperidine (1 nM to 1 microM) showed no effects on Na+ channels. The blockade of Na+ and delayed rectifier K+ channels could not be antagonized by the addition of naloxone. It is concluded that meperidine has a nonselective inhibitory action on Na+ and K+ channels of amphibian peripheral nerve. For tonic Na+ channel block, neither an opioid receptor nor the the local anesthetic agent binding site is the target site for meperidine block.

Effect of mexiletine on spontaneous sensory afferent activity in spontaneous diabetic rats (WBN/Kob rats)

In this study, we investigated the hypothesis that mexiletine has an inhibitory action on spontaneous sensory afferent activity caused by small fiber neuropathy in diabetic rats (WBN/Kob rats). Gastric administrations of mexiletine (10 mg in 0.3 ml saline) and the local anesthetic agent lidocaine (10 mg in 0.3 ml saline) were made in urethane-anesthetized rats. In 6 of 7 WBN/Kob rats (57-62 weeks of age), spontaneous afferent activity was observed and was significantly inhibited after administration of mexiletine, whereas it was not seen in either WBN/Kob rats (54 weeks of age) or Wistar SLC rats (31 and 35 weeks of age). This inhibitory action of mexiletine was sustained for more than 2 h after the administration. In contrast, lidocaine administration also inhibited the spontaneous nerve activity, but the magnitude of the inhibitory action was less than that of mexiletine. In another experiment, the afferent conductance velocity of the sural nerve was not affected after mexiletine was administrated in the WBN/Kob rats (62 weeks of age). The results suggest that pain mitigation of a diabetic prescribed with mexiletine may depend on the inhibitory effect of mexiletine on the generation of the spontaneous afferent action potentials by mexiletine in aged WBN/Kob rats, whereas mexiletine has no effect on the autonomic function of the afferent nerve.

Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging.

Changes in metabolism and local circulation occur in the spinal cord during peripheral noxious stimulation. Evidence is presented that this stimulation also causes signal intensity alterations in functional magnetic resonance images of the spinal cord during formalin-induced pain. These results indicate the potential of functional magnetic resonance imaging in assessing noninvasively the extent and intensity of spinal cord excitation in this well characterized pain model. Therefore, the aim of this study was to establish functional magnetic resonance imaging as a noninvasive method to characterize temporal changes in the spinal cord after a single injection of 50 microl of formalin subcutaneously into the hindpaw of the anesthetized rat. This challenge produced a biphasic licking activity in the freely moving conscious animal. Images of the spinal cord were acquired within 2 min, enabling monitoring of the site and the temporal evolution of the signal changes during the development of formalin-induced hyperalgesia without the need of any surgical procedure. The time course of changes in the spinal cord functional image in the isoflurane-anesthetized animal was similar to that obtained from behavioral experiments. Also, comparable physiological data, control experiments, and the inhibition of a response through application of the local anesthetic agent lidocaine indicate that the signal changes observed after formalin injection were specifically related to excitability changes in the relevant segments of the lumbar spinal cord. This approach could be useful to characterize different models of pain and hyperalgesia and, more importantly, to evaluate effects of analgesic drugs.

Sulfur dioxide-induced bronchoconstriction via ruthenium red-sensitive activation of sensory nerves.

The mechanism of sulfur dioxide-induced bronchoconstriction was studied using isolated perfused and ventilated guinea-pig lungs. They were exposed to sulfur dioxide after pretreatment with different compounds, either via the pulmonary artery or via the air passages. Neither the cyclooxygenase inhibitor indomethacin (30 microM) nor the H1-receptor antagonist diphenhydramine (15 microM), given via the perfusate, attenuated the sulfur dioxide-induced bronchoconstriction. Furthermore, sulfur dioxide exposure did not cause a release of either thromboxane or histamine into the perfusate. In experiments with atropine equivocal results were obtained with regard to protection against sulfur dioxide-evoked bronchoconstriction. Intratracheal instillation of the local anesthetic agent lidocaine (1 mg/50 microliters) markedly reduced the sulfur dioxide-induced bronchoconstriction. Also, ruthenium red (10 microM), an agent with calcium entry-blocking properties and an inhibitor of capsaicin-induced bronchoconstriction, was able to inhibit the effect of sulfur dioxide. The sulfur dioxide-induced bronchoconstriction was associated with release of calcitonin gene-related peptide, a sensory neuropeptide. The effect of sulfur dioxide was also inhibited by a Ca(2+)-free buffer plus EGTA. These results suggest that sulfur dioxide-induced bronchoconstriction in the guinea-pig lung is the result of a local effect on sensory nerves (C-fiber activation). The mechanism seems to be dependent on the Ca(2+)-dependent release of sensory neuropeptides and to be linked to opening of the cation channel, which is associated with the proposed capsaicin receptor on sensory nerves as revealed by the inhibitory effect of ruthenium red.

The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers.

The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.

The role of pH in the development of tachyphylaxis to local anesthetic agents.

Evidence for tachyphylaxis to the local anesthetic agents lidocaine and mepivacaine has been found in a study of continuous caudal anesthesia in obstetrical patients. Seduced response to these drugs is shown to be independent of the increasing pain of labor. An experimental study of tachyphylaxis in the dog was undertaken, utilizing 14C-lidocaine and 24C-procaine administered by a continuous spinal technique. Repeated injections of the acid anesthetic salt were associated with continued decreases in pH of the cerebrospinal fluid and proportionate increases in the concentration of local anesthetic- Calculations of the percentages of the free base form (lipid-soluble) indicated significant shifts with minor changes in pH. It is suggested that tachyphylaxis to local anesthetic agents may be associated with changes in pH and shifts in the amounts of ionized and nonionized forms. The limited buffer reserve available in the cerebrospinal fluid (and presumably, the extradural space) makes these areas especially vulnerable.