Use of lidocaine with phenylephrine (Co-phenylcaine) spray for anaesthesia of the external auditory canal.

OBJECTIVE: A method is described for topical local anaesthesia of the tympanic membrane and ear canal using lidocaine and phenylephrine (Co-phenylcaine) spray and soaked micropatties. DISCUSSION: The advantages of this method are discussed in comparison to existing methods.

Effects of generally recognized as safe (GRAS) and dietary compounds on phenylephrine metabolism in LS180 human intestinal cells.

Phenylephrine (PE) has low and variable oral bioavailability in humans, due in part to presystemic metabolism by sulfation. LS180 cells were used as a model of the human intestinal epithelium to examine phenylephrine metabolism and its inhibition by generally recognized as safe (GRAS) and dietary compounds. Curcumin, zingerone, resveratrol, guaiacol, pterostilbene and isoeugenol significantly inhibited phenylephrine disappearance, while vanillin, propylparaben and eugenol did not. However, when propylparaben was combined with either vanillin or eugenol, the phenylephrine disappearance was significantly inhibited. These data suggest that these compounds or combinations thereof may have potential to improve phenylephrine oral bioavailability.

Co-Phenylcaine Spray: can we improve the taste? A randomised, double-blind, crossover study.

OBJECTIVE: Co-Phenylcaine Forte is a nasal spray routinely prescribed by otolaryngologists in Australia. The taste of Co-Phenylcaine Forte is typically described as unpleasant. This study sought to improve the overall patient experience associated with Co-Phenylcaine Forte by generating a Co-Phenylcaine Forte formulation, referred to as Co-Phenylcaine Zest, which contains an added vanilla flavour and masking agent. METHODS: Participants were randomised to receive two actuations of Co-Phenylcaine Forte in each nostril followed by two actuations of Co-Phenylcaine Zest, or vice versa. There was a 6-36-hour washout period between each treatment. After the administration of each spray, participants completed a questionnaire to rate various sensory attributes of each formulation on seven-point ordinal scales. Patients reported their overall formulation preference after receiving both treatments. RESULTS: A total of 86 participants completed the trial. Seventy-four per cent of patients preferred Co-Phenylcaine Zest, 21 per cent preferred Co-Phenylcaine Forte and 5 per cent had no preference (p < 0.001). The satisfaction score associated with Co-Phenylcaine Zest was 1.22 points greater than with Co-Phenylcaine Forte (p < 0.001). CONCLUSION: A novel formulation of Co-Phenylcaine Forte was created by adding a flavour and a masking agent; this formulation was preferred by most patients.

Relationship between the phenylephrine test and eyelid droop after aponeurotic repair with the use of an epinephrine-containing local anaesthetic.

PurposeTo analyse the relationship between the results of the phenylephrine test and postoperative eyelid droop in transcutaneous aponeurotic repair using epinephrine-containing local anaesthetic for aponeurotic blepharoptosis.Patients and methodsWe retrospectively reviewed the medical records of 66 eyelids from 40 patients who underwent transcutaneous aponeurotic repair. A positive phenylephrine test result was defined as an increase in margin reflex distance-1 (MRD-1) ≥0.5 mm after application of phenylephrine eye drops. The patients were divided into a positive phenylephrine response group (Group A, 16 patients) and a negative phenylephrine response group (Group B, 24 patients). The ΔMRD-1 was calculated by subtracting the 3-month postoperative value from the intraoperative value. Patient age, sex, pre- and intraoperative MRD-1s, levator function, and phenylephrine response were investigated as factors potentially influencing the ΔMRD-1. The relationship between these factors and ΔMRD-1 was analysed using single and multiple regression analysis.ResultsThe ΔMRD-1 in Group A (0.68±0.52 mm) was significantly greater than that in Group B (0.17±0.56 mm; P=0.004). A moderate correlation was found between phenylephrine response and ΔMRD-1 in the total patient group (YΔMRD-1=0.441 Xphenylephrine+0.358; r=0.462; r2=0.213; P=0.002).ConclusionsAlthough the ΔMRD-1 in Group B was quite small, the ΔMRD-1 in Group A was considerable, and there was a moderate positive correlation between phenylephrine response and the ΔMRD-1 overall. This indicates that the degree of postoperative eyelid droop can be estimated by the phenylephrine test results in transcutaneous aponeurotic repair.

Gastrodin causes vasodilation by activating KATP channels in vascular smooth muscles via PKA-dependent signaling pathway.

Gastrodin, one of the major components extracted from the Chinese herb Gastrodia elata Bl., has been widely used as an anticonvulsant, sedative, analgesic and hypotensive. In our study, we aimed to investigate the effects and possible mechanisms of gastrodin on vascular KATP channels. Tension experiments were used on rat mesenteric artery rings without an endothelium. Patch clamp experiments were executed to investigate the influences of gastrodin on the membrane current in mesenteric artery smooth muscle cells. Gastrodin induced vasorelaxation in a concentration dependent manner when rat mesenteric artery rings were pre-contracted with Phenylephrine. The vasorelaxation effect was partially diminished by pre-treating with a KATP channel inhibitor, or a PKA inhibitor. With whole-cell patch-clamp recording techniques, we found that gastrodin is a activator of KATP in rat mesenteric artery smooth muscle cells, and this effect was eliminate by pre-treating with H89or PKI, PKA inhibitor. In addition, when rat vascular smooth muscle cells were treated with 100 µM gastrodin for 24 h, maximum KATP current density increased by 28.1%. The results indicate that gastrodin exerts vasorelaxation effect through activation of PKA and subsequent opening of smooth muscle KATP channels.

A stepwise approach to the induction of idiopathic fascicular ventricular tachycardia.

PURPOSE: Noninducibility of the clinical tachycardia is a major limitation while mapping and ablating idiopathic fascicular ventricular tachycardia (FVT). There is very little data on systematic induction protocols in this entity. Our aim was to study the role of systematic induction protocols in patients with clinically documented ventricular tachycardia (VT). METHODS: Programmed electrical stimulation was performed at baseline from high right atrium, right ventricular apex, right ventricular outflow tract and from left ventricle as per the protocol. Programmed ventricular stimulation was performed at two drive cycle lengths up to three extrastimuli and short-long-short sequence. If FVT remained non inducible at baseline, pharmacological provocation with isoprenaline/atropine/phenylephrine was used based on the baseline atrio-ventricular Wenckebach cycle length. RESULTS: This systematic induction protocol was studied in 68 patients with clinically documented FVT and sustained FVT was inducible in 64 patients (94 %). Of these 64 patients, pharmacological provocation was required in 18 patients (28 %) while in the remaining, sustained VT was induced at baseline. This high induction rate allowed ablation during tachycardia, which resulted in 100 % acute procedural success in the patients where sustained tachycardia could be induced. At a follow up of 29 ± 13 months, two patients (3 %) had recurrence. CONCLUSIONS: Systematic induction protocol along with the appropriate use of pharmacological agents results in a high induction rate of FVT. This may result in more defined and limited ablation during tachycardia with better success rates and lesser recurrence.

Mydriasert pupillary dilation for cataract surgery: an economic and clinical study.

BACKGROUND: Mydriasert is an insoluble ophthalmic insert indicated for mydriasis prior to cataract surgery, which gradually releases the active ingredients: tropicamide (0.25 mg) and phenylephrine (5.38 mg). This study aimed to evaluate the cost of Mydriasert compared with conventional mydriatic eye drops to induce pupil dilation prior to cataract surgery using a budget impact model. METHODS: A cohort-based, decision tree, budget impact model was developed to estimate the drug, consumable and staff costs for achieving mydriasis with Mydriasert compared to mydriatic eye drops (tropicamide [1%] plus phenylephrine [10%]). Insights from structured interviews with clinicians (n = 5) experienced in using both Mydriasert and mydriatic eye drops and results from the current clinical study of patients undergoing cataract surgery (n = 144) at a Greater London district general hospital were used to obtain key input parameters for the model, and to validate the model approach. RESULTS: The base case analysis in a cohort of 1763 patients undergoing cataract surgery showed that when Mydriasert substituted mydriatic eye drops, annual total costs decreased by 18% and annual total nurse time decreased from 235.1 hours to 44.1 hours over one year (2012-2013). CONCLUSIONS: This study demonstrated that despite its higher unit cost than mydriatic eye drops, Mydriasert resulted in overall savings in health-care costs, mainly associated with reduced nursing time. The economic model developed could assist National Health Service managers and local payers to estimate the budget impact of the introduction of Mydriasert into different clinical settings.

Extra-cerebral oxygenation influence on near-infrared-spectroscopy-determined frontal lobe oxygenation in healthy volunteers: a comparison between INVOS-4100 and NIRO-200NX.

INTRODUCTION: Frontal lobe oxygenation (Sc O2 ) is assessed by spatially resolved near-infrared spectroscopy (SR-NIRS) although it seems influenced by extra-cerebral oxygenation. We aimed to quantify the impact of extra-cerebral oxygenation on two SR-NIRS derived Sc O2 . METHODS: Multiple regression analysis estimated the influence of extra-cerebral oxygenation as exemplified by skin oxygenation (Sskin O2 ) on Sc O2 in 21 healthy subjects exposed to whole-body exercise in hypoxia (Fi O2  = 12%; n = 10) and normoxia (n = 12), whole-body heating, hyperventilation (n = 21), administration of norepinephrine with and without petCO2 -correction (n = 15), phenylephrine and head-up tilt (n = 7). Sc O2 was assessed simultaneously by NIRO-200NX (Sniro O2 ) and INVOS-4100 (Sinvos O2 ). Arterial (Sa O2 ) and jugular bulb oxygen saturations (Sj O2 ) were obtained. RESULTS: The regression analysis indicated that Sinvos O2 reflects 46% arterial, 14% jugular, 35% skin and 4% oxygenation of tissues not interrogated. Sinvos O2 follows a calculated estimate of cerebral capillary oxygenation (r = 0·67; P<0·0001). In contrast, the NIRO-200NX-determined Sc O2 did not correlate with the estimate of cerebral oxygenation (r = 0·026; P = 0·71). CONCLUSION: For all interventions, 35% of the INVOS-4100 signal reflected extra-cerebral oxygenation while, on the other hand, NIRO-200NX did not follow changes in a calculated estimate of cerebral capillary oxygenation. Thus, the NIRO-200NX and INVOS-4100 do not provide for unbiased evaluation of the cerebral signal.

Palpebral position interdependence in blepharoptosis: comparison of the effect of instillation of 10% phenylephrine drop and digital lifting / Interdependência na posição palpebral em ptose palpebral: comparação do efeito de instilação de colírio de fenilefrina 10% e o teste de elevação digital da pálpebra

Purpose: To quantify and compare the effects of instillation with 10% phenylephrine and digital lifting on the contralateral upper eyelid of patients with involutional bilateral blepharoptosis. Methods: The present prospective clinical study involved patients with involutional bilateral blepharoptosis who underwent two tests: 1) digital lifting of the more ptotic eyelid and observation of the effect on the contralateral eyelid and 2) instillation of two drops of 10% phenylephrine in the more ptotic eye and observation of the effect on the contralateral eyelid. Patients were filmed before and 5, 10, and 15 min after instillation, and the resulting images were analyzed to obtain eyelid measurements. The results were tested using a linear mixed-effects model. Results: A total of 27 patients, ranging from 52 to 82 years of age (mean age 68.51 ± 8.21 years), 24 (88.88%) of whom were women, were included in the present study. In eyes that received instillation, the marginal distance reflex-1 (MDR1) values increased from baseline (1.21 ± 0.60 mm) until 10 min after instillation, then remained statistically unchanged until 15 min after instillation (2.42 ± 0.90 mm). Significant differences were observed in the contralateral eye of the group that underwent digital lifting (1.51 ± 0.53 mm - 1.63 ± 0.56 mm) and in the contralateral eye of the group that underwent 10% phenylephrine instillation (1.38 ± 0.54 mm - 1.63 ± 0.56 mm); p=0.02 and p<0.01, respectively. Conclusion: In all eyes, 10% phenylephrine elevated the upper eyelid, with improved eyelid height at 10 min after instillation. Significant differences were observed in the height of the contralateral eyelid when compared before and after each intervention in each group; however, this difference was very small and nearly undetectable by conventional clinical evaluation in the digital lifting group. However, the 10% phenylephrine eye-drop test resulted in substantial changes in MDR1 values ...

Objetivo: Quantificar e comparar o efeito da instilação do colírio de fenilefrina 10% com o levantamento manual da pálpebra superior contralateral de pacientes com ptose palpebral bilateral involucional. Métodos: Estudo clínico e prospectivo de pacientes com ptose palpebral bilateral involucional submetidos a dois testes: 1) elevação manual da pálpebra mais ptótica e observação do efeito da intervenção na pálpebra contralateral; e 2) a instilação de duas gotas de colírio de fenilefrina 10% no olho mais ptótico e observação do efeito da intervenção na pálpebra contralateral. Os pacientes foram filmados antes e 5, 10 e 15 minutos após a instilação. Os resultados foram analisados estatisticamente com o modelo linear de efeitos mistos. Resultados: O estudo incluiu 27 pacientes com idade entre 52-82 anos (68,51 ± 8,21), 24 dos quais eram do sexo feminino (88,88%). Em olhos submetidos a instilação do colírio, os valores da DMR1 (distância marginal reflexo) aumentaram da linha de base (1,21 ± 0,60 mm) até os 10 min, em seguida, manteve-se estatisticamente estável até 15 min (2,42 ± 0,90 mm). Diferenças significativas foram observadas nos olhos contralaterais, independentemente do levantamento manual da pálpebra (1,51 ± 0,53 mm - 1,63 ± 0,56 milímetros) e da instilação do colírio de fenilefrina 10% (1,38 ± 0,54 mm - 1,63 ± 0,56 mm), p=0,02 e p<0,01 respectivamente. Conclusões: Em todos os olhos, a instilação do colírio de fenilefrina 10% mostrou um aumento gradual do valor de distância marginal reflexo até os 10 min. Nos olhos contralaterais houve diminuição do valor de distância marginal reflexo, independentemente do teste realizado, porém as mudanças que ocorrem na posição da pálpebra contralateral, durante o teste da elevação manual, são muito pequenas e difíceis de serem detectadas no exame clínico convencional. Enquanto isso, o teste de colírio de fenilefrina 10% produziu mudanças substanciais nos valores distância marginal reflexo nos ...

Phenylephrine potentiates the anticonvulsant effect and neutralizes the sedative effect of diazepam in rats upon combined intragastric administration.

High doses of phenylephrine and diazepam (1 and 10 mg/kg, respectively) suppressed the development of generalized tonic-clonic pentylenetetrazole-induced convulsions in 86-100% rats, but did not prevent local clonic pentylenetetrazole-induced convulsions. Diazepam in the specified dose produced strong sedation, while phenylephrine had no sedative effect in the open-field test. Combined intragastric administration of phenylephrine in a medium and individually ineffective dose (0.3 mg/kg) and diazepam in a high dose (10 mg/kg) potentiated the anticonvulsant effect of diazepam: it prevented not only tonic-clonic, but also clonic pentylenetetrazole-induced convulsions in 100% rats and 2.6-fold increased anticonvulsant activity of diazepam. The specified combination of diazepam and phenylephrine had no sedative effect. The mechanism of potentiation of the anticonvulsive effect and elimination of the sedative side effect is based on stimulation of gastric mucosa afferents by phenylephrine.

Anaesthetic plus dilating gel improves pupil dilation for cataract surgery.

OBJECTIVE: To evaluate the efficacy of a combination anaesthetic plus dilating gel (ADG) on pupil dilation (PD) and corneal anaesthesia (KA) compared to traditional preoperative pharmacotherapy for cataract surgery. DESIGN: Prospective, noninferiority study. METHODS: We studied 20 consenting adults who experienced unilateral cataracts and underwent routine cataract surgery, receiving the traditional preoperative pharmacologic regimen in the operated eye (control eye): diclofenac 0.1%, gentamicin 0.3%, cyclopentolate 1%, phenylephrine 2.5%, and tropicamide 1% 60 and 20 minutes prior to surgery. They then received tetracaine 0.5% and povidone-iodine 5% 10 minutes prior to surgery; and were given tetracaine 0.5%, povidone-iodine 5%, and lidocaine 2% gel 1 minute prior to surgery. Epinephrine 0.1%, 1 cc per 500 mL bag of balanced saline salt solution was administered during surgery. The nonoperated eye (study eye) received tetracaine 0.5%, povidone-iodine 5%, and 0.35 cc ADG gel (phenylephrine 10%, tropicamide 1%, diclofenac 0.1%, and lidocaine 2%) 60 and 10 minutes prior to surgery. PD and KA were measured at baseline, at 30 minutes, and at 5 minutes prior to surgery, and at 5 minutes after surgery. RESULTS: There was no difference in PD (p = 0.2634) or KA (p = 0.6058) between the study eyes and the control eyes at baseline. Preoperatively, greater mydriasis was achieved in the study eye (7.95 ± 0.91 mm vs 7.17 ± 1.25 mm; p < 0.0001). There was no significant difference in preoperative KA between the study and control eyes (1.5 ± 2.2 mm vs 1.4 ± 2.1 mm; p = 0.77). CONCLUSIONS: The combination ADG for preoperative preparation of cataract patients achieves at least equivalent dilation and corneal anaesthesia as the current preoperative pharmacologic regimen.

Paradoxical change in atrial fibrillation dominant frequencies with baroreflex-mediated parasympathetic stimulation with phenylephrine infusion.

INTRODUCTION: Parasympathetic stimulation is known to promote atrial fibrillation (AF) through shortening of atrial refractory periods. We hypothesized that baroreflex-mediated parasympathetic stimulation via phenylephrine (PE) infusion would increase AF rate as measured by dominant frequency (DF). METHODS AND RESULTS: The protocol was performed in 27 patients (24 M, 59 ± 1 years old) prior to AF ablation. For 10 patients in AF, PE was infused until systolic blood pressure increased ≥30 mmHg. Electrograms were recorded in the left atrium before and after PE. DFs of each recording were calculated offline. Atrial effective refractory periods (ERPs) were measured before and after PE in 11 patients who were in sinus rhythm during the procedure. DFs were also measured in 6 patients in AF before and after complete parasympathetic blockade with atropine (0.04 mg/kg). PE resulted in increased RR intervals during sinus rhythm (1,170 ± 77 to 1,282 ± 85 ms, P = 0.03) and AF (743 ± 32 to 826 ± 30 ms, P = 0.03), consistent with parasympathetic effect on the sinus and AV nodes, respectively. DFs were decreased by PE in the left atrium (6.2 ± 0.2 to 6.0 ± 0.2 Hz, P = 0.004). Correspondingly, atrial ERPs significantly increased from 218 ± 13 to 232 ± 11 ms (P = 0.04). Atropine resulted in a decreasing trend in DF in the left atrium (5.9 ± 0.1 to 5.8 ± 0.1 Hz, P = 0.07). CONCLUSIONS: Despite baroreflex-mediated parasympathetic effect, PE produced a slowing of AF along with lengthening of ERP, while parasympathetic blockade also slowed DF. It is therefore likely that the direct and indirect adrenergic effects of PE on atrial electrophysiology are more prominent than its parasympathetic effects.

Delayed intraocular pressure elevation after pupillary dilation in exfoliation syndrome.

PURPOSE: To determine the effect of pupillary dilation on intraocular pressure (IOP) in normotensive patients with exfoliation syndrome (XFS). METHODS: Patients with XFS were enrolled in this prospective trial. All eyes were untreated, had no previous laser or operative surgery and were normotensive with full visual fields and open angles. IOP was measured before dilation and hourly for four consecutive hours after dilation with tropicamide 1% and phenylephrine 2.5% eyedrops. RESULTS: Twenty-five eyes of 19 White patients (nine male, 10 female) with XFS were enrolled. Twelve eyes (48%) had a rise in IOP of ≥ 4 mmHg above the pre-dilation baseline IOP and four (16%) had a rise of ≥ 9 mmHg (9-28 mmHg). Post-dilation gonioscopy confirmed the presence of an open anterior chamber angle in all eyes. The maximum IOP was reached 3 hr post-dilation in three eyes and after 2 hr in the remaining eyes. The four eyes with marked IOP rise exhibited an elevation of between 1 and 7 mmHg at 1 hr. Extensive pigment release was noticed in all eyes that had a rise in IOP. CONCLUSION: Patients with XFS are at risk of developing delayed post-dilation IOP rises. Awareness of this phenomenon is particularly important in patients with advanced cupping and/or severe visual field loss who may not be able to tolerate a marked elevation of IOP. An early, mild rise in IOP at 1 hr may serve as a warning sign for a more severe, delayed response. Eyes with XFS should be monitored carefully after dilation, especially those with marked pigment release.

Prospective, randomized, controlled clinical trial of Ankaferd Blood Stopper in patients with acute anterior epistaxis.

This is a study evaluating the efficacy of Ankaferd Blood Stopper (ABS) as a hemostatic agent compared to hemostasis by phenylephrine in patients with anterior epistaxis. The study design is a prospective, randomized, controlled, nonblinded, clinical trial. In total, 49 patients were randomly seperated to receive hemostasis technique by means of either ABS wet tampon or phenylephrine impregnated gauze tampon for anterior epistaxis control. Patients were crossed over to the other technique after two unsuccessful attempts of the first technique. Measured outcomes such as number of applications, relationship of number of applications with bleeding intensity (1 = stains on napkin, 2 = soaked napkin, 3 = bowl needed), patient discomfort during hemostasis (0 = none, 9 = unbearable), and complications were assessed. Additional data were recorded for rebleeding within 7 days. 24 of the 49 patients were assigned to the new ABS group (group I) and remaining 25 were included in the standard phenylephrine group (group II). ABS was more effective than phenylephrine at control of anterior epistaxis (79.2 vs. 64%, p < 0.05). For the patients who crossed over from phenylephrine to ABS, 44.4% achieved hemostasis by ABS. ABS successfully treated all bleeding intensity 1 and 2 patients with one application (5 min). ABS patients experienced fewer rebleeding rates within 7 days compared to phenylephrine patients (8.3 vs. 20%, p < 0.05). The patients for which ABS was applied, significant differences in effective control of anterior epistaxis were observed compared to phenylephrine. ABS is effective, safe, quick, and easy alternative to the phenylephrine in patients with anterior epistaxis.

Investigating the effects of high-dose phenylephrine in the management of prolonged ischaemic priapism.

INTRODUCTION: Acute priapism can be managed by corporal blood aspirations and the instillation of alpha adrenergic agonists such as phenylephrine if patients present early. Following prolonged ischaemic priapism, this regimen is often unsuccessful, and the use of phenylephrine is limited due to systemic cardiovascular side effects. AIM: To investigate the effects of high-dose phenylephrine on human corpus cavernosal smooth muscle obtained from patients presenting with refractory ischaemic priapism. METHODS: Strips of corpus cavernosum were obtained from six patients presenting with prolonged ischaemic priapism (duration 60-240 hours), where detumescence was refractory to conventional doses of phenylephrine. The smooth muscle contractile response to high doses of phenylephrine were then compared with that of normal control corpus cavernosum obtained from four patients undergoing a penectomy for penile cancer. The tissue was then analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) to assess its viability. MAIN OUTCOME MEASURES: The in vitro response to high-dose phenylephrine of corpus cavernosum smooth muscle obtained from patients with refractory priapism compared with normal human corpus cavernosum. RESULTS: Corporal blood gas analysis confirmed hypoxia (pO(2) 1.5-2.3 kPa), acidosis (pH 6.9-7.1), and glucopenia (0-0.3 mmol/L) in all six patients confirming the ischaemic nature of the priapism. Application of high doses of phenylephrine produced a marked muscle contraction in the control tissue, but there was no contractile response at all in any of the priapism patients. Analysis with TUNEL indicated widespread smooth muscle cell apoptosis in all the priapism tissue. CONCLUSIONS: This study has shown that patients with ischaemic priapism that fails to respond to conventional doses of an alpha-agonist are unlikely to benefit from continual or high-dose phenylephrine administration, as there is usually widespread apoptosis of the cavernosal smooth muscle preventing further contraction.

Transient allodynia pain models in mice for early assessment of analgesic activity.

BACKGROUND AND PURPOSE: The most common preclinical models of neuropathic pain involve surgical ligation of sensory nerves, which is especially difficult in mice. Transient models of chemically sensitized allodynia are potentially useful for rapidly characterizing the analgesic profile of compounds and conducting mechanistic studies. EXPERIMENTAL APPROACH: Increasing doses of NMDA, sulprostone (an EP1/EP3 prostaglandin receptor agonist) or phenylephrine (an alpha (1) adrenoceptor agonist) were injected intrathecally (i.t.) or i.p., and animals were subsequently assessed for allodynia. The effects of receptor antagonists and analgesic compounds on allodynia were also assessed. KEY RESULTS: A comparison of total body doses that cause allodynia following spinal or systemic administration indicated that NMDA induces allodynia in the spinal cord while sulprostone and phenylephrine act through a peripheral mechanism. Inhibition of the allodynia with receptor antagonists indicated that each agent induces allodynia by a distinct mechanism. The three models were benchmarked using compounds known to be active in neuropathic pain patients and nerve injury animal models, including gabapentin, amitriptyline and clonidine. CONCLUSIONS AND IMPLICATIONS: These transient allodynia models are a useful addition to the toolbox of preclinical pain models. They are simple, rapid and reproducible, and will be especially useful for characterizing the pain phenotype of knockout mice.