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Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs). Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6-C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50 Hz, 0.2 ms, 2-4V, 5 min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABA(A)), saclofen (GABA(B)), ketanserine (5HT(2)), methysergide (5HT(1-2)), phentolamine (α-adrenergic), propranolol (β-adrenergic), sulpiride (D(2)/D(3) dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation. Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems., (Copyright © 2012 IBRO. All rights reserved.)

Objectives: To assess whether long-term users of intracavernous (IC) injections after radical prostatectomy can switch to oral therapy with sildenafil citrate., Methods: Forty-nine patients (mean age 60.9 years) with erectile dysfunction after radical prostatectomy were identified as long-term users of IC injections (3.7 +/- 1.9 years). These patients received open-label treatment with sildenafil citrate (50 to 100 mg) for a minimum of 4 weeks or five attempts. The primary outcome measure of our study was assessed by the Sexual Health Inventory of Men (SHIM) questionnaire (International Index of Erectile Function-5 [IIEF]). A successful switch was prospectively defined as erection sufficient for vaginal penetration after sildenafil use and compliance to therapy. Patients were designated as responders or nonresponders on the basis of their ability to achieve vaginal penetration., Results: Of 49 patients, only 36 agreed to receive oral open-label sildenafil (50 to 100 mg) for a minimum of 4 weeks or five attempts. Prostaglandin E1 (PGE1) was used in 70% and triple therapy (PGE1, papaverine, and phentolamine) in the remaining 30%. Of the 36 patients, 15 (41%) successfully switched to sildenafil and discontinued IC injections. When the results were stratified by the type of IC solution, patients with high-dose triple therapy had a poor success rate of switch (7%) compared with patients using PGE1 treatment (67%). Of the 36 patients, 14 (38%) found sildenafil ineffective and continued using IC injections. Patients who switched to oral therapy had had a greater (P <0.001) total mean SHIM (IIEF-5) score with IC injections than those who did not switch (12.3 +/- 7.8 versus 20.0 +/- 4.9). Of the 36 patients, 7 (19%) found sildenafil alone to be suboptimal but continued using it, enhancing the efficacy of IC injections alone. The three predictive factors for a successful switch were high preoperative SHIM (IIEF-5) score, high post-IC injection SHIM score, and type of IC medication used (PGE1 alone versus high-dose triple therapy)., Conclusions: Long-term users of IC injection therapy can potentially switch to sildenafil citrate with acceptable sexual satisfaction. Patients will accept a lower degree of sexual satisfaction as measured by the IIEF-5 (SHIM) score if oral therapy is effective.

Objective: The aim of the present study was to evaluate the therapeutic potency of an electrotherapy of striated ischiocavernous muscles in patients with erectile dysfunction., Patients and Methods: Transcutaneous electrostimulation of striated ischiocavernous muscles by self-adhesive penile or perineal skin electrodes was performed in 48 patients with erectile dysfunction. 6/48 patients (R) responded to intracavernous pharmacotherapy while 42/48 (NR) did not show significant penile rigidity even to intracavernous papaverine/phentolamine/PGE1 triple drug medication., Results: Within the observation time of 3 months, 10/48 patients dropped out. 22/38 patients reported a penile rigidity for sufficient sexual intercourse whereby 3/22 NR required additional intracavernous pharmacotherapy. Penile rigidity could be objectivated by triple drug medicaton in 12/14 NR after ischiocavernous muscle stimulation (EIS) therapy. 5/6 R were treated successfully for premature erection loss. During EIS treatment neither discomfort nor complications could be observed., Conclusion: Transcutaneous electrostimulation of ischiocavernous muscles is a new, noninvasive therapy for the improvement of penile rigidity. The clinical results underline the importance of the striated ischiocavernous muscles for penile rigidity.

Objectives: Patients experiencing erectile dysfunction who fail intracavernous injection (ICI) therapy are commonly believed to have exhausted pharmacologic options. We evaluated the efficacy and safety of transurethral alprostadil (MUSE) in patients experiencing erectile dysfunction who underwent prior ICI therapy (alprostadil, papaverine, phentolamine, or a combination of these)., Methods: Of the 1511 patients enrolled in a multicenter trial of transurethral alprostadil, 452 (30%) reported prior ICI therapy and its effects. These patients tested up to four dose levels of transurethral alprostadil in the clinic, and those who achieved an erection satisfactory for intercourse were treated at home in a double-blind, placebo-controlled trial., Results: Prior ICI therapy was reported to be "not effective" by 95 of 452 patients (21%), "sometimes effective" by 119 of 452 (26%), and "effective" by 238 of 452 (53%). In patients reporting ICI therapy as "not effective," 58% achieved an erection sufficient for intercourse following transurethral alprostadil therapy in the clinic; 47% of these responsive patients reported successful sexual intercourse after transurethral alprostadil therapy during home treatment. For patients reporting ICI therapy as "sometimes effective" or "effective," 68% achieved an erection sufficient for intercourse following transurethral alprostadil therapy in the clinic setting and 67% of these responsive patients reported successful intercourse following transurethral alprostadil therapy at home. Few adverse effects were encountered. The most common adverse effect was penile pain, which occurred with 7.8% of administrations., Conclusions: Transurethral alprostadil therapy is an effective therapeutic option for patients with erectile dysfunction and may even "rescue" some patients who have failed prior intracavernous injection therapy.

Objectives: To evaluate the results of treating patients with cavernosal venous leakage (CVL) with polyagent self-administered intracavernous pharmacotherapy and vacuum constriction devices (VCDs)., Methods: One hundred eighty-eight chronically impotent patients with a mean age of 58.8 years were studied. This group comprised 103 patients treated with standard-dose and high-dose polyagent self-administered intracavernous pharmacotherapy and 85 patients treated with a VCD. The erectile response was related to the severity of CVL (mild, moderate, and severe)., Results: With standard polyagent pharmacotherapy, a response sufficient for satisfactory intercourse was achieved in 18 of 32 patients with mild CVL, 9 of 54 patients with moderate CVL, and in 0 of 17 patients with severe CVL. With high-dose polyagent pharmacotherapy, a response sufficient for satisfactory intercourse was achieved in 22 of 32 patients with mild CVL, 29 of 54 patients with moderate CVL, and in 2 of 17 patients with severe CVL. With a VCD, a response sufficient for satisfactory intercourse was achieved in 23 of 30 patients with mild CVL, 24 of 40 patients with moderate CVL, and in 10 of 15 patients with severe CVL., Conclusions: CVL of mild to moderate severity can be treated with polyagent pharmacotherapy and VCDs with reasonable expectations of success. Severe CVL responds poorly to polyagent pharmacotherapy but can be treated with VCDs with reasonable results in motivated, adequately instructed patients.

Objectives: Recently, nitric oxide was shown to be a mediator of penile erection in men and the nitric oxide donor linsidomine chlorhydrate (SIN-1) was introduced as a novel treatment option in patients with erectile dysfunction. We now present our follow-up results with the intracavernous application of SIN-1., Methods: One hundred thirteen patients with erectile dysfunction of various etiologies and 10 normal control subjects underwent intracavernous pharmacotesting with 1 mg SIN-1. Of the 113 patients, 71 (62.8%) underwent additional pharmacotesting with a mixture of papaverine (15 mg/mL) and phentolamine (0.5 mg/mL) (P/P). Forty-eight responders to SIN-1 were enrolled in an autoinjection program with this substance., Results: All normal control subjects had full rigid erections lasting 40 to 70 minutes. Of 113 patients, 78 (69%) had responses sufficient for intercourse with SIN-1, and the other 35 patients (31%) demonstrated inadequate responses. All 44 responders to SIN-1 who also received P/P had erections sufficient for intercourse with P/P in doses of 0.25 to 2 mL (mean, 0.6 +/- 0.3 mL). Six patients (13.6%) had prolonged erections with minimal to moderate doses of P/P. From the total of 27 patients who had erections insufficient for intercourse with SIN-1, 20 (74.1%) had good responses with 0.25 to 2.0 mL P/P (mean, 1.5 +/- 0.5 mL). One patient (4%) had a prolonged erection with 1.0 mL P/P: After 10 to 150 injections/patient (total of 1160 injections; mean, 24.1 injections), no significant side effects were noted with SIN-1., Conclusions: Our data suggest that intracavernous SIN-1 is safe and efficacious in the majority of patients with erectile dysfunction; however, it has a lower smooth muscle relaxing effect than a combination of P/P. The absence of severe side effects, including priapisms, may be explained by the use of a physiologic pathway for induction of the erectile response and the rapid intracavernous decomposition of SIN-1.

We investigated the effects of intraperitoneal administration of adrenoceptor antagonists to the hyperthermia and hyperglycemia induced by prostaglandin F2 alpha (50 micrograms) injected into the third cerebral ventricle in anesthetized rats. Phentolamine inhibited the hyperthermia and hyperglycemia induced by prostaglandin F2 alpha. Prazosin inhibited the hyperthermia induced by prostaglandin F2 alpha, while enhancing the hyperglycemia. Yohimbine inhibited the prostaglandin F2 alpha-induced hyperglycemia without an effect on the hyperthermia. Propranolol had no effect on either prostaglandin F2 alpha-induced hyperglycemia or hyperthermia. These observations suggest that the hyperglycemia induced by prostaglandin F2 alpha is regulated by alpha 2-adrenoceptor systems while the hyperthermia is regulated by alpha 1-adrenoceptor systems in rats.

Erections are inhibited by sympathetic stimulation. Anxiety or psychologic inhibition may produce abnormal response during impotence workup. The use of intracorporeal alpha blockers (phentolamine) and audiovisual sexual stimulation (AVSS) has been used to decrease sympathetic outflow and enhance erectile response. Thirty-three patients with suspected vasculogenic impotence were studied. They underwent pulsed Doppler ultrasound (PDUS) with multiple doses of tri-mix (mix of papaverine, phentolamine, and prostaglandin E1). AVSS was applied after maximal response to tri-mix. Seventeen patients (51.5%) responded to multidose with grade IV or V erection. When AVSS was started, 5 more patients responded, and 7 upgraded to grade V with overall response of 40 percent. AVSS can augment the in-office response to pharmacologic testing above that obtained by "maximal" pharmacologic dosing, thereby increasing the sensitivity and specificity of the test.

Thirty-eight men aged 26-69 years (mean 58) who failed to achieve a full, sustained erection with intracavernosal injections of papaverine and phentolamine (PIPE) and who had evidence of a venous leak on digital subtraction dynamic cavernosography underwent penile vein ligation. Postoperative follow-up ranged from 7 to 44 months (mean 28). Nineteen patients regained spontaneous erections which would allow intercourse (mean follow-up on these men was 23 months). Of these 19 patients, 5 experienced recurrent loss of potency over a 6- to 17-month period (mean 9 months), 4 of these subsequently responding to intracavernosal therapy. Of the 19 without full erections after ligation, 8 obtained erections which would allow intercourse with intracavernosal injections. Two of these patients subsequently lost their response to injections at 2 and 6 months postoperatively. Eleven men had no benefit from surgery (either with or without injections). Of the total of 27 men with erections allowing intercourse, only 19 made an attempted coitus during the follow-up period. Of 9 men with treatment failure who had undergone repeat cavernosography, 8 had evidence of a persistent leak, usually arising from the cavernosal veins. At the time of this study, 4 men had been re-explored, following which 3 obtained erections with the aid of PIPE. Patients who fail to improve following ligation may benefit from re-investigation and repeat ligation using a different surgical approach.

Thirty-three diabetic men were instructed in the use of phentolamine-papaverine injections for the treatment of erectile dysfunction over a two-year period. Of these, 12 reported a satisfactory response and 21 reported a nonsatisfactory response. The responders and the nonresponders were retrospectively studied to identify characteristics that would predict a satisfactory response. No difference was found between the two groups in the duration of diabetes, the presence of retinopathy, neuropathy, nephropathy, peripheral vascular disease, or ischemic heart disease. The utilization of insulin, the prevalence of type II diabetes, or the use of drugs which would cause impotence, did not differ between the two groups. There was no difference in the serum testosterone levels between the two groups. Age was the only predictive factor. Only 1 of 14 patients over age sixty had a satisfactory response to treatment while 11 of 19 patients under age sixty had a satisfactory response. Five of the responders and 2 of the nonresponders proceeded to penile implant surgery and reported satisfactory results. While older diabetic men may choose a trial of intracorporeal injections, they should be counselled regarding the high failure rate and alternative forms of therapy.

This study directly compared two nonsurgical treatments for erectile dysfunction, self-injection of papaverine/phentolamine and external vacuum devices, in terms of usage rates, effectiveness, side effects, dropout rates, and impact on patient sexual and psychologic functioning. Both alternatives were regularly, successfully, and safely used by patients, though dropout rates were higher for self-injection. Both produced erections of improved quality, and effected sustained improvements in frequency of intercourse, orgasm, and sexual satisfaction. Spontaneous erections also improved with both treatments. General psychiatric symptomatology was decreased, and anxiety was improved. There were no differences between the two treatments in sexual or psychologic impact. Relative contraindications and esthetic considerations are presented.

At certain centers, microsurgical penile revascularization, using different surgical techniques, has gained importance throughout the past years. In general, only patients classified as intracavernous injection nonresponders are subjected to this kind of surgery. Since 1988, revascularization surgery has been performed at our clinic on 19 intracavernous injection nonresponders. The Hauri technique was carried out on the first 6 patients. The last 10 patients underwent modified anastomosis surgery. The inferior epigastric artery and the dorsal penile artery are anastomosed, one behind the other, end-to-side, to the dorsal penile vein. This results in a more simple procedure with assurance of flow. The Virag technique was performed on 3 patients. 18 patients achieved erections with or without the aid of intracavernous injections (at a mean follow-up of 13.4 months). 11 patients were capable of spontaneous erections, whereby it was particularly noted that 8 of the 10 patients undergoing the modified technique achieved spontaneous erections. The results demonstrate that intracavernous injection nonresponders benefit from revascularization surgery.

After reviewing the pharmacological and physiological basis for the treatment of benign prostatic hypertrophy (BPH) symptoms with alpha 1-adrenergic blockers, the authors analyze the clinical trials published in the literature. The indications, doses, side effects and contraindications for the alpha 1 blockers in the treatment of BPH are summarized.

Eight patients with impotence following radical cystectomy and ileal loop surgery for cancer of the bladder were treated with a mixture of papaverine/phentolamine at 30/1 ratio. All but 1 patient had a successful result. In the majority of patients the duration of the erection was significantly less than in impotent patients with different causations.

156 patients undergoing intracavernosal autoinjection pharmacotherapy for periods of 2-36 months were studied for the effect of treatment on self-esteem, performance anxiety, partnership and acceptance using a semi-structured questionnaire. Replies were received from 86.3% of the patients. 93% gave a very good, good or satisfactory rating of intracavernosal pharmacotherapy. 78.2% indicated that their self-esteem had grown. 79.4% said that performance anxiety diminished in the course of therapy (25.6%) or disappeared entirely (53.8%). 71.8% of the replies confirm the positive effect of treatment on marital relations or partnership. 61.9% of the patients used intracavernosal pharmacotherapy permanently. 28.3% needed therapy intermittently or at large intervals only, and 4.5% (7 patients) were cured of their chronic sexual dysfunction. When preceded by thorough multidisciplinary diagnostics and careful patient selection, intracavernosal pharmacotherapy constitutes an efficient mode of treatment for chronic erectile dysfunction.

Intracavernous administration of papaverine and phentolamine has become an essential and indispensible element in the diagnosis and treatment of erectile dysfunction. This paper assesses the frequency and meaning of the main side effects of intracavernous injections (prolonged erections, fibrosis, etc.). It is concluded that the benefit from this new method definitely exceeds the possible risks. However, for the safe implementation of this method, close and intensive cooperation between the physician and his patient is a condition that has to be guaranteed. Each patient carrying out autoinjection therapy has to be examined at reasonable intervals to evaluate the to date unknown effects of long-term therapy.

Thirty-three patients with erectile failure were taught to self-inject papaverine intracavernosally. The dose was from 15 to 80 mg. Phentolamine was added if 80 mg was not sufficient. The patients kept a diary on the effects of the regimen, and also filled out a questionnaire after a follow-up of 4-16 months. The results showed that 55% were satisfied with the method. However, technical difficulties were common. Sexual stimulation turned out to be very important resulting in varying erections on consecutive occasions with the same papaverine dose. Prolonged erection occurred once in 5 patients and was easily handled conservatively in all. Fibrous plaques developed in 2 patients. Twelve patients (36%) stopped the injections for various reasons. When failure occurred the disappointment was usually severe. Thus, the selection of patients for self-injection is important.