Infiltrative Cutaneous Analgesia Research Articles

N(Omega)-nitro-l-arginine methyl ester potentiates lidocaine analgesic and anaesthetic effect in rats.

The purpose of the experiment was to study the effect of L-NAME (N(Omega)-nitro-L-arginine methyl ester) and its cotreatment with lidocaine on the spinal block and infiltrative cutaneous analgesia. The quality of cutaneous analgesia was examined by the block of the cutaneous trunci muscle reflexes following needle stimuli in the rat. Spinal anaesthetic potency was assessed by measuring three neurobehavioral examinations of nociceptive, proprioceptive and motor function following intrathecal injection in the rat. L-NAME (0.6, 6 and 60 nmol) when cotreatment with lidocaine (ED50) produced dose-related cutaneous analgesia. Coadministration of L-NAME (0.6 μmol) with lidocaine intensified (P < 0.01) and prolonged (P < 0.001) cutaneous analgesia, whereas subcutaneous L-NAME (0.6 μmol) and saline did not provoke cutaneous analgesic effects. Adding L-NAME (2.5 μmol) to lidocaine intrathecally prolonged spinal sensory and motor block (P < 0.01), while intrathecal L-NAME (2.5 μmol) or 5% dextrose (vehicle) produced no spinal block. L-NAME at 60 nmol (the minimum effective dose) increases and prolongs the effect of cutaneous analgesia of lidocaine. L-NANE at an ineffective dose potentiates lidocaine analgesic and anaesthetic effects.

Beta-blocker carteolol and oxprenolol produce cutaneous analgesia in response to needle pinpricks in the rat

ABSTRACT Background This present study was undertaken to determine whether beta-blockers produce the cutaneous analgesic effect, comparing them with the long-acting local anesthetic bupivacaine. Methods Using a rat model of infiltrative cutaneous analgesia, the effect of 5 beta-blockers (oxprenolol, carteolol, butaxamine, metoprolol, and acebutolol) and bupivacaine was compared and eventually combined with epinephrine. Results Among 5 beta-blockers, oxprenolol exhibited the most potent and the longest duration of cutaneous analgesia. In dose-response studies, the rank order of efficacy (ED50 [50% effective dose]) was bupivacaine (0.40 [0.35–0.47] μmol) > oxprenolol (2.33 [2.06–2.64] μmol) > carteolol (4.86 [4.27–5.53] μmol) (p< 0.01). Carteolol provoked a longer duration of analgesia (p< 0.01) than oxprenolol or bupivacaine on an equipotent basis (ED25, ED50, and ED75). Adding epinephrine 1:200,000 to drug preparations (carteolol, oxprenolol, and bupivacaine) at ED95 had a peripheral action in prolonging the duration of action. Conclusions Oxprenolol and carteolol had greater potencies and longer durations of cutaneous analgesia than butaxamine, metoprolol, and acebutolol. Oxprenolol produced a similar duration of action when compared to bupivacaine, while carteolol had a greater duration of action than bupivacaine. Cutaneous analgesia of oxprenolol (or carteolol) plus adrenaline was greater than that of bupivacaine plus adrenaline.

Chlorpheniramine produces cutaneous analgesia in rats.

This study sought to assess the cutaneous (peripheral) analgesic effects of antihistamine chlorpheniramine, compared with the long-lasting local anesthetic bupivacaine. After chlorpheniramine and bupivacaine were subcutaneously injected under the dorsal skin of the rats, the cutaneous analgesia effect was quantitatively evaluated by scoring the number to which the animal failed to react (cutaneous trunci muscle reflex). The quality and duration of chlorpheniramine and bupivacaine on infiltrative cutaneous analgesia were compared. We revealed that subcutaneous chlorpheniramine, as well as the local anesthetic bupivacaine elicited cutaneous analgesia in a dosage-dependent manner. Based on their ED50s (50% effective doses), the relative potency was found to be chlorpheniramine [1.13 (1.05-1.22) μmol] < bupivacaine [0.52 (0.46-0.58) μmol] (p < 0.01). When comparing the ED25s, ED50s and ED75s, full recovery time induced by chlorpheniramine was longer (p < 0.01) than that induced by bupivacaine. Our preclinical data demonstrated that both chlorpheniramine and bupivacaine dose-dependently provoked the cutaneous analgesic effects. Chlorpheniramine with a more prolonged duration was less potent than bupivacaine in inducing cutaneous analgesia.

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.

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED25, ED50 and ED75), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.

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.

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92–2.09] μmol/kg) greater than dopamine (190 [181–203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect.

Clonidine as an adjuvant for propranolol enhances its effect on infiltrative cutaneous analgesia in rats

Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose-dependent, and both propranolol (9.0μmol) and bupivacaine (1.8μmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42–0.55) μmol] greater than propranolol [2.27 (1.98–2.54) μmol] (p<0.01). Subcutaneous saline and clonidine (0.12μmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12μmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia.

Subcutaneous l-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats

The purpose of the study was to estimate the ability of l-tyrosine to induce cutaneous analgesia and to investigate the interaction between l-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with l-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug–drug interaction was analyzed by using an isobolographic method. We showed that both l-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88–5.38]μmol)>l-tyrosine (39.1 [36.5–41.8]μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by l-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with l-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that l-tyrosine elicits the local/cutaneous analgesia, and the interaction between l-tyrosine and lidocaine is additive. l-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding l-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone.

Propranolol combined with dopamine has a synergistic action in intensifying and prolonging cutaneous analgesia in rats.

The purpose of the experiment was to assess interactions of dopamine with propranolol as an infiltrative anesthetic. After injecting the rats with four doses of drugs subcutaneously, the cutaneous analgesic effect of propranolol was compared with dopamine through the blockade of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick. Drug-drug interactions were examined via an isobolographic analysis. We demonstrated that the action of propranolol and dopamine was dose dependent to skin infiltrative analgesia. On the ED(50) (50% effective dose) basis, the rank of drug potency was propranolol (11.3 [10.6-12.2]μmol) > dopamine (195 [188-205]μmol) (p < 0.001). At the equi-anesthetic doses (ED(25), ED(50), ED(75)), the block duration caused by dopamine was equal to that caused by propranolol. Coadministration of dopamine and propranolol exhibited a synergistic effect on infiltrative cutaneous analgesia. The preclinical data showed that dopamine produced a lesser potency but a comparable duration of cutaneous analgesia compared to propranolol. Adding dopamine to propranolol potentiated and prolonged propranolol's cutaneous analgesic effect.

Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat

BackgroundThe purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. MethodsCutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. ResultsOn the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95–4.18)μmol]>lidocaine [5.81 (5.70–5.98)μmol] (p<0.01). Clonidine at a dose of 0.12μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. ConclusionsOur resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine.

Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats

The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95–2.21)μmol/kg]>propranolol [9.21 (9.08–9.42)μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.

Co-administration of memantine with epinephrine produces a marked peripheral action in intensifying and prolonging analgesia in response to local skin pinprick in rats

The purpose of this study was to examine the effect of epinephrine as adjuvant for memantine or lidocaine as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we evaluated the effects of adding epinephrine to memantine or lidocaine on infiltrative cutaneous analgesia. Lidocaine, a known local anesthetic, was used as control. We found that epinephrine, memantine, and lidocaine produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. On a 50% effective dose (ED50) basis, the relative potencies were epinephrine [0.012 (0.006–0.020)μmol]>memantine [4.010 (3.311–4.988)μmol]>lidocaine [6.177 (5.333–7.218)μmol] (P<0.05 for each comparison). Mixtures of epinephrine (2.7nmol or 13.7nmol) with drugs (memantine or lidocaine) at ED50 or ED95, respectively, enhanced the potency and prolonged the duration of action on infiltrative cutaneous analgesia. Intraperitoneal injection of co-administration of drugs (memantine or lidocaine) at ED95 with epinephrine (13.7nmol) produced no cutaneous analgesia (data not shown). Epinephrine, memantine, and lidocaine were shown to have local anesthetic effects as infiltrative cutaneous analgesia. Epinephrine increased the duration and potency of memantine and lidocaine as an infiltrative anesthetic.

Diphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat

Although diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long-lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose-dependent fashion. We showed that diphenhydramine, as well as bupivacaine displayed a dose-dependent cutaneous analgesia in response to dorsal cutaneous noxious stimuli. The relative potency (50% effective dose) was bupivacaine (0.023 [0.013-0.035]%)>diphenhydramine (0.078 [0.068-0.091]%; P<0.001). On an equipotent basis, diphenhydramine had a similar duration of action to bupivacaine. Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.

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.

Cutaneous Analgesia and Systemic Toxicity of Carbetapentane and Caramiphen in Rats

Caramiphen produces spinal anesthesia; caramiphen and carbetapentane have never been tested as infiltrative cutaneous analgesic. The aim of this study was to compare cutaneous analgesia of caramiphen and carbetapentane with bupivacaine and evaluated their central nervous system and cardiovascular toxicity. After the blockade of cutaneous trunci muscle reflex with subcutaneous drug injections in rats, we evaluated the local anesthetic effect of carbetapentane and caramiphen on infiltrative cutaneous analgesia. After continuous intravenous infusion of equipotent doses of bupivacaine, carbetapentane, caramiphen, and saline, we observed mean arterial blood pressure and heart rate and monitored the onset time of seizure, apnea, and impending death. Carbetapentane and caramiphen acted like bupivacaine and elicited cutaneous analgesia in a dose-related fashion. On a 50% effective dose (ED50) basis, the ranks of potencies were bupivacaine (1.78 [1.52-2.07]) > carbetapentane (2.53 [2.38-2.77]) > caramiphen (3.60 [3.41-3.99]) (P < 0.01). At equianalgesic doses (ED25, ED50, ED75), the duration caused by carbetapentane or caramiphen was similar to that caused by bupivacaine. Under equipotent doses, the infusion time of carbetapentane or caramiphen required to cause seizure, apnea, and impending death was longer than that of bupivacaine (P < 0.05). The decline in mean arterial blood pressure and heart rate was slower with carbetapentane or caramiphen when compared with bupivacaine (P < 0.01 for the differences) at equipotent doses. Carbetapentane and caramiphen were similar to bupivacaine at producing durations of cutaneous analgesia but were less likely than bupivacaine to induce central nervous system and cardiovascular systemic toxicity.

Nisoxetine produces local but not systemic analgesia against cutaneous nociceptive stimuli in the rat

The aim of this study was to evaluate the local anesthetic effect of nisoxetine as infiltrative cutaneous analgesic. After rats were injected subcutaneously with nisoxetine, dose–response curves were constructed. The cutaneous anesthetic effect of nisoxetine or MK-801 (dizocilpine) was compared with lidocaine, a traditional local anesthetic. We found that nisoxetine and MK-801 acted like lidocaine and elicited dose-related cutaneous (local) anesthesia. The relative potency was nisoxetine > MK-801 > lidocaine ( P < 0.01) as infiltrative anesthesia of skin. On an equianesthetic doses (20% effective dose [ED 20], ED 50, and ED 80), nisoxetine produced longer action of cutaneous anesthesia than that of lidocaine or MK-801 ( P < 0.01). Coadministration of nisoxetine or lidocaine with MK-801 showed an additive cutaneous anesthesia. Neither local injection of a large dose of nisoxetine, MK-801 nor lidocaine in the thigh area produced cutaneous anesthesia (data not shown). In conclusion, nisoxetine had a local anesthetic effect as infiltrative cutaneous analgesia with durations of actions longer than that of lidocaine or MK-801. That N-methyl- d-aspartate receptors may not contribute to the cutaneous (local) anesthetic effect of nisoxetine or lidocaine.

The Local Anesthetic Effect of Memantine on Infiltrative Cutaneous Analgesia in the Rat

Memantine blocks N-methyl-D-aspartate receptors and the Na(+) current, one principal mechanism of local anesthesia. Until now, no study mentioned that memantine had a local anesthetic effect, and therefore we investigated the local anesthetic effect of memantine. After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the cutaneous analgesic effect of memantine, lidocaine, and dizocilpine (MK-801) in rats. The dose-dependent response of memantine on cutaneous analgesia was compared with lidocaine and MK-801 in rats. The duration of action for each drug was evaluated and compared on an equipotent basis (20% effective dose [ED(20)], ED(50), and ED(80)). Lidocaine, a frequently used local anesthetic, was used as control. We demonstrated that memantine, lidocaine, and MK-801 produced dose-dependent local anesthetic effects as infiltrative cutaneous analgesia. The relative potency was MK-801 (10.4 [9.7-11.1]) > memantine (17.6 [15.2-20.4]) > lidocaine (25.9 [23.8-28.1 ]) (P < 0.01). On an equipotent basis, memantine showed longer duration than lidocaine (P = 0.012) and MK-801 (P = 0.008). Coadministration of memantine (13.3 μmol/kg) and MK-801 (1.3 μmol/kg) produced greater blockade and duration than memantine (13.3 μmol/kg) or MK-801 (1.3 μmol/kg) alone. Neither local injection of saline nor intraperitoneal administration of a large dose of memantine, lidocaine, or MK-801 produced cutaneous analgesia (data not shown). This study indicated that memantine is less potent than MK-801, and that memantine elicits longer analgesic duration than both lidocaine and MK-801. When combined with MK-801, memantine demonstrates a synergetic effect of cutaneous analgesia. We conclude that memantine produces better local analgesia than lidocaine and that N-methyl-D-aspartate receptors also contribute to the analgesic effect of memantine.

Clonidine as adjuvant for oxybuprocaine, bupivacaine or dextrorphan has a significant peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats

The aim of the study was to evaluate co-administration of clonidine with oxybuprocaine (ester type), bupivacaine (amide type) or dextrorphan (non-ester or non-amide type) and to see whether it could have a peripheral action in enhancing local anesthesia on infiltrative cutaneous analgesia in rats. Cutaneous analgesia was evaluated by a block of the cutaneous trunci muscle reflex (CTMR) in response to local dorsal cutaneous noxious pinprick in rats. The analgesic effect of the addition of clonidine with oxybuprocaine, bupivacaine or dextrorphan by subcutaneous injection was evaluated. On an ED50 basis, the rank of drug potency was oxybuprocaine>bupivacaine>dextrorphan (P<0.01). Mixtures of clonidine (0.12μmol) with oxybuprocaine, bupivacaine or dextrorphan (ED50 or ED95) extended the duration of action and increased the potency on infiltrative cutaneous analgesia. Among these drugs, the addition of clonidine to bupivacaine (amide type) elicits the most effective cutaneous analgesia. Clonidine at the dose of 0.12 and 0.24μmol did not produce cutaneous analgesia. Oxybuprocaine showed more potent cutaneous analgesia than bupivacaine or dextrorphan in rats. Co-administration of oxybuprocaine, bupivacaine or dextrorphan with clonidine increased the potency and duration on infiltrative cutaneous analgesia. The addition of clonidine to bupivacaine (amide type) elicits more effective cutaneous analgesia than oxybuprocaine (ester type) or dextrorphan (non-ester or non-amide type).

Isobolographic Analysis of Epinephrine With Bupivacaine, Dextromethorphan, 3-Methoxymorphinan, or Dextrorphan on Infiltrative Anesthesia in Rats: Dose-Response Studies

The aims of this study were to establish the potencies of epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan and evaluate interactions of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. Bupivacaine, a common and long-acting local anesthetic, was used as control. Dose-dependent responses of epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan on cutaneous analgesia were compared with bupivacaine in rats. The interactions of drugs were evaluated via an isobolographic analysis. We found that epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. Relative potencies were epinephrine > bupivacaine > dextromethorphan > 3-methoxymorphinan > dextrorphan (P < .01 for each comparison). Coadministration of bupivacaine with epinephrine produced a synergistic effect, and coadministration of dextromethorphan, 3-methoxymorphinan, or dextrorphan with epinephrine produced an additive effect. Epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan are known to have local anesthetic effects as infiltrative cutaneous analgesia in rats. Epinephrine increased the potency of bupivacaine, but not dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. The cutaneous analgesic effects of adding epinephrine to dextromethorphan, 3-methoxymorphinan, or dextrorphan, are similar to combinations of 2 local anesthetics.