Enriched enrollment randomized double-blind placebo-controlled cross-over trial with phenytoin cream in painful chronic idiopathic axonal polyneuropathy (EPHENE): a study protocol.

Background: Patients with chronic idiopathic axonal polyneuropathy (CIAP) can have neuropathic pain that significantly impacts quality of life. Oral neuropathic pain medication often has insufficient pain relief and side effects. Topical phenytoin cream could circumvent these limitations.

Pulsed Radiofrequency Increases Nestin and Matrix Metalloproteinase-2 Expression in Porcine Lumbar Dorsal Root Ganglion.

Background: Pulsed radiofrequency (PRF) has been used for the treatment of chronic lumbar radicular pain and other chronic pain states. The dorsal root ganglion (DRG) consists of primary afferent somatic and visceral nerve cell bodies that transduce sensory signals from the periphery to the central part of the nervous system. It is a very important part of acute nociception, as well as the development and maintenance of chronic pain.

Study Design Characteristics and Endpoints for Enriched Enrollment Randomized Withdrawal Trials for Chronic Pain Patients: A Systematic Review.

Enriched enrollment randomized withdrawal (EERW) pain trials are designed to include only responders with considerable pain relief without unacceptable side effects into the randomized phase. There are no recommendations for primary endpoints in such trials. Our objective was to propose recommendations based on assessment of trial characteristics, endpoints and effect sizes in EERW pain trials.

No Detectable Phenytoin Plasma Levels After Topical Phenytoin Cream Application in Chronic Pain: Inferences for Mechanisms of Action.

Purpose: Topical phenytoin can act as an analgesic in chronic pain, but it is unclear if topical phenytoin gives rise to systemic side effects. Therefore, the aim of this study is: 1) to evaluate safety in chronic pain patients who used topical phenytoin up to 30% applied daily on intact skin and mucous membrane, through determining phenytoin plasma levels; and 2) to elaborate on the analgesic mechanism of action.

Patients And Methods: In this retrospective study, we collected demographic and clinical data from 33 chronic pain patients who used 10% to 30% phenytoin cream, and in whom blood samples were drawn for phenytoin concentration measurement between January 2017 until September 2020.

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.

Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients' quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences.

Post-traumatic stress disorder symptoms and pain intensity in persons with spinal cord injury.

Study Design: Cross-sectional.

Objectives: To examine the association between post-traumatic stress disorder (PTSD) symptoms and pain intensity, taking symptoms of anxiety and depression into account within persons with spinal cord injury (SCI).

Setting: Persons with SCI, who visited a Dutch rehabilitation centre between 2005 and 2010, were invited to complete a survey.

Neuropathic pain in spinal cord injury: topical analgesics as a possible treatment.

Study Design: Review of the literature and semi-structured interviews.

Objective: To explore the possible use of topical analgesics for the treatment of neuropathic pain (NP) in spinal cord injury (SCI).

Setting: Institute for Neuropathic Pain, Soest, The Netherlands.

Usefulness of a Double-Blind Placebo-Controlled Response Test to Demonstrate Rapid Onset Analgesia with Phenytoin 10% Cream in Polyneuropathy.

Purpose: Topical analgesics are an upcoming treatment option for neuropathic pain. In this observational study, we performed a double-blind placebo-controlled response test (DOBRET) in patients with polyneuropathy to determine the personalized analgesic effect of phenytoin 10% cream.

Patients And Methods: In a double-blind fashion, 12 consecutive adult patients with symmetrical painful polyneuropathy and equal pain intensity of ≥4 on the 11-point numerical rating scale (NRS) applied phenytoin10% cream on one painful area and a placebo cream on the corresponding contralateral area.

Phenytoin Cream for the Treatment of Sciatic Pain: Clinical Effects and Theoretical Considerations: Case Report.

Chronic sciatic pain is difficult to treat. Patients often suffer from considerable pain and are severely hampered in their everyday activities. Most pharmacologic analgesic treatments have disappointing effects, and often are limited due to adverse events.

Topical loperamide for the treatment of localized neuropathic pain: a case report and literature review.

Peripheral nerve damage can result in neuronal hyperexcitability, resulting in neuropathic pain. Localized neuropathic pain is confined to a specific area not larger than a letter-size piece of paper. Topical analgesics are increasingly popular for the treatment of localized neuropathic pain because systemic agents for managing neuropathic pain often produce undesirable and intolerable side effects.

Podiatric Adverse Events and Foot Care in Cancer Patients and Survivors .

Cancer is one of the leading causes of mortality and morbidity worldwide. Recent improved therapies have resulted in more patients surviving cancer and living longer. Despite these advances, the majority of patients will develop adverse events from anticancer therapies.

Ethical justification of single-blind and double-blind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings.

At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests.

Single-Blind Placebo-Controlled Response Test with Phenytoin 10% Cream in Neuropathic Pain Patients.

Background: Phenytoin cream applied topically has been explored in neuropathic pain conditions. In several case series, phenytoin 5% and 10% cream could reduce pain in a clinically relevant way with a fast onset of action within 30 min, and with positive effects on sleep.

Objective: To evaluate a single-blind placebo-controlled response test (SIBRET) for use in clinical practice.

Phenytoin Cream for the Treatment for Neuropathic Pain: Case Series.

Background: Neuropathic pain can be disabling, and is often difficult to treat. Within a year, over half of all patients stop taking their prescribed neuropathic pain medication, which is most probably due to side effects or disappointing analgesic results. Therefore, new therapies are needed to alleviate neuropathic pain.

Phenytoin: neuroprotection or neurotoxicity?

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis.

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design.

Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient.

Topical phenytoin for the treatment of neuropathic pain.

We developed and tested a new putative analgesic cream, based on the anticonvulsant phenytoin in patients suffering from treatment refractory neuropathic pain. The use of commercial topical analgesics is not widespread due to the facts that capsaicin creams or patches can give rise to side effects, such as burning, and analgesic patches (e.g.

Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action.

In 1908 phenytoin (5,5-diphenylhydantoin) was first synthesized as a barbiturate derivative in Germany by professor Heinrich Biltz (1865-1943) and subsequently resynthesized by an American chemist of the pharmaceutical company Parke-Davis in 1923 in Detroit. Screening phenytoin did not reveal comparable sedative side effects as barbiturates and, thus, Parke-Davis discarded this compound as a useful drug. In 1936, phenytoin's anticonvulsive properties were identified via a new animal model for convulsive disorders, developed by Putnam and Merritt, who also evaluated its clinical value in a number of patients in the period 1937-1940.

Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics.

Treatment of neuropathic pain using topical formulations is still in its infancy. Only few topical analgesic formulations have become available for clinical use, and among these, analgesic creams are still rare. This is unfortunate because analgesic creams offer a number of advantages over patches, such as convenience, ease of adapting the frequency of application, and dose, and "rubbing cream where it hurts" involves the patient much more in the therapeutic process compared to patches and other localized treatment modalities.

Autologous tumor immunizing devascularization of an invasive colorectal cancer: A case report and literature review.

Colorectal cancer is the third most common cancer. Approximately 20% of patients have at the time of presentation metastasized colorectal cancer, which is incurable in ~80% of cases. The present case report describes a typical case diagnosed with an advanced invasive colorectal adenocarcinoma, with two suspect hypodense lesions in the liver, as revealed by sonography.

New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells.

Topical treatments of localized neuropathic pain syndromes in general are mostly neglected, mainly due to the fact that most pain physicians expect that a topical formulation needs to result in a transdermal delivery of the active compounds. On the basis of the practical experience, this study brings forth a new, somewhat neglected element of the vulvodynia pathogenesis: the cross talk between the nerve endings of nociceptors, the adjacent immunocompetent cells, and vaginal epithelial cells. Insight into this cross talk during a pathogenic condition supports the treatment of vulvodynia with topical (compounded) creams.

Autologous tumor immunizing devascularization in cancer therapy.

Tumor vaccination depending on specific antigens, autologous tumor vaccination involving wide range of antigens, immunomodulating cytokines and bacterial agents have been studied extensively with the purpose of stimulating the antitumor immune response. Unfortunately these therapies showed disappointing results mainly due to undesirable mechanisms tending to dampen the antitumor immune response. We will discuss a novel approach of autologous tumor immunization using a surgical technique: autologous tumor immunizing devascularization (ATID).

Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy.

Retinopathy is a threat to the eyesight, and glaucoma and diabetes are the main causes for the damage of retinal cells. Recent insights pointed out a common pathogenetic pathway for both disorders, based on chronic inflammation. Palmitoylethanolamide (PEA) is an endogenous cell protective lipid.