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For over a thousand years, various substances have been applied to the skin to treat pain. Some of these substances have active ingredients that we still use today. However, some have been discontinued due to their harmful effect, while others have been long forgotten. Recent concerns regarding the cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. There is increasing evidence of the efficacy and safety of topical agents in pain control. Topical analgesics are great alternatives for pain management and are an essential part of multimodal analgesia. This review aims to describe essential aspects of topical drugs that physicians should consider in their practice as part of multimodal analgesia. This review describes the mechanism of popular topical analgesics and also introduces the most recently released and experimental topical medications.

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. We defined responders as patients who experienced a pain reduction ≥2 NRS points from baseline and ≥1 NRS point difference in pain reduction in favour of phenytoin 10% cream compared with placebo cream within 30 minutes after application. We also evaluated the percentage of pain reduction and frequency of 30% and 50% pain relief from baseline. Results Six patients (50%) were responders. Compared with placebo cream, pain reduction was higher in phenytoin 10% cream-applied areas with mean difference in pain reduction of 1.3 (95% CI: 1.1 to 1.8; p

Neuropathische Schmerzen sind eine therapeutische Herausforderung. Topisch wirksame Analgetika haben zwar den Vorteil geringer Nebenwirkungen, allerdings fehlen weitgehend Daten uber ihre Langzeiteffektivitat. Folglich wurden mit Topika behandelte Patienten in der eigenen Klinik befragt. Ethik: 16-5690, DRKS: 00011877. In den Jahren 2008–2017 erhielten 265 Patienten mit neuropathischem Schmerz mindestens eine Therapie mit Capsaicin 8 % (C), Lidocain 5 % (L) und/oder perineuralem Botulinumtoxin‑A (B), von denen 205 (77 %) telefonisch standardisiert zu Schmerz (erste/letzte Therapie: gering/mittel/sehr gut), moglicher Analgetikareduktion sowie evtl. Abbruchgrunden befragt wurden (Interviewzeitpunkt C: 26 ± 19, L: 61 ± 23, B: 11 ± 6 Monate nach Beginn). Daten zur Vorbehandlung sowie Diagnosen wurden dem hauseigenen Dokumentationssystem entnommen. Als Responder bzw. Langzeitresponder wurden Patienten mit mindestens „mittlerer“ Schmerzreduktion bei der ersten Behandlung bzw. der letzten Behandlung eingestuft, sofern diese eine adaquate Zeit anhielt. In allen Behandlungsgruppen (56 ± 13 Jahre, 62 % mannlich; C: 80, L: 84, B: 58 Patienten) uberwogen Patienten mit langer Schmerzanamnese (C: 60 ± 73, L: 59 ± 66, B: 67 ± 71 Monate) und hoher Schmerzintensitat (C: 7 ± 2, L: 7 ± 2, B: 6 ± 2 NRS). Unter L war die primare und langfristige Responderrate am hochsten (57 %/60 %, B: 52 %/37 %, C: 23 %/15 %). Unter B konnten Langzeitresponder am haufigsten Analgetika reduzieren (74 %, C: 58 %, L: 38 %). Trotz langer Krankheitsdauer hatten die zumeist im „off label use“ angewendeten Topika L und B im Gegensatz zu C eine hohe primare Ansprechrate, wobei die meisten von einer Dauertherapie profitierten.

Pain is a complex and unique experience. It encompasses several pathways, involving nociceptive signal generation (transduction) and propagation (transmission), as well as perception and modulation of the nociceptive stimuli. Nonsteroidal anti-inflammatory drugs (NSAIDs) primarily exert their analgesic effects through inhibition of cyclooxygenase (COX) enzymes, thereby attenuating prostaglandin synthesis. The COX-2 selective NSAIDs (coxibs) and aspirin have also been shown to reduce colorectal cancers, presumably by prostaglandin-inhibition mechanisms. Paracetamol appears to have both peripheral and central effects. The postulated mechanism for its peripheral effects is indirect COX inhibition, while the central effects are thought to be mediated by modulation of descending pain inhibition pathways. Topical analgesics are available in various formulations. The topical NSAIDs have the same mechanism of action as the systemic formulations, but with less systemic absorption and effects. The local anaesthetics provide a dense sensory block via inhibition of nerve impulse transmission, and are available in percutaneous and transdermal preparations. Capsicum is effective for neuropathic pain, and acts by stimulating and then desensitising peripheral sensory nerves.

Topical analgesics are a non-opioid option for the treatment of chronic pain conditions including neuropathic pain, musculoskeletal pain, and osteoarthritis. There are many topical medications available; however their efficacy is variable. This article reviews the various topical analgesics, their mechanisms of action, and their efficacy. Studies have found topical NSAIDs are useful in treating acute musculoskeletal pain syndromes (strains and sprains) and show some efficacy in treating hand and knee osteoarthritis (Derry et al. Cochrane Database Syst Rev 5:CD008609, 2017). Topical capsaicin 8% has been shown to be efficacious in the treatment of postherpetic neuralgia, painful diabetic peripheral neuropathy, and HIV-neuropathy (Derry et al. Cochrane Database Syst Rev 1:CD007393, 2017). Topical lidocaine has been widely studied and found to reduce pain in patients with postherpetic neuralgia (Knezevic et al. Pain Manag 7:537–58, 2017). Although many other topical analgesics are available, there is limited data to support the efficacy of other agents. Topical analgesics are a relatively benign treatment for chronic pain conditions including neuropathic pain, musculoskeletal, and myofascial pain. There is evidence to support the use of topical NSAIDs, high concentration topical capsaicin, and topical lidocaine for various painful conditions.

The discovery and development of effective analgesics is greatly lagging behind the steadily rising prevalence of chronic pain. Currently prescribed analgesics for chronic pain are lacking in efficacy mainly due to their narrowly-targeted mechanism of action. Driving neuronal hyperexcitability that underlies symptoms of chronic pain are multiple non-neuronal processes, among which are tissue hypoxia and oxidative stress. Here we demonstrate the design, synthesis, and activity of new multi-component bi-functional analgesic crystalline solids, co-crystals, and salts, based on pairing of vasodilatory anti-hypoxic drugs pentoxifylline, clonidine and linsidomine with antioxidant nutraceuticals protocatechuic acid, &alpha, lipoic acid, and caffeic acid. After validation, chemical and structural characterization of these novel salts and co-crystals, topical formulations of the products were tested in a rat model of complex regional pain syndrome. Analgesic effects achieved with the salts and co-crystal exceeded the efficacy and/or potency of constituent compounds indicating that more effective, advanced analgesics can readily be developed by careful pairing of compounds that simultaneously target multiple neural and non-neural processes driving chronic pain.

Adequate pain control is a major concern in the immediate postoperative period. In multiple strategies for postoperative pain management, topical analgesics have significant advantages of minimizing severe side effects caused by oral and parenteral administration and drug-drug interactions. Therefore, we studied the effect of lidocaine patch on postoperative pain control in laparoscopic appendectomy.This randomized double-blind prospective controlled study enrolled 40 acute appendicitis cases that were treated by laparoscopic appendectomy and randomly divided into two groups. Lidocaine patches containing lidocaine 175 mg was applied to the umbilical trocar site of each patient, and pain intensity was assessed with the visual analog scale every 6 hours up to 48 hours after laparoscopic appendectomy.There was no significant difference in age, gender, body mass index, the American society of anesthesiologists score, comorbidity, or underlying disease between the lidocaine patch and control groups. The postoperative pain scores were lower in the lidocaine patch group than in the control group, but statistical significance was not noted at the trocar site or the right lower quadrant of the abdomen (P = .320 and P = .903, respectively). The mean amounts of pethidine used after surgery were significantly smaller in the lidocaine patch group than in the control group (0.10 ± 0.31 mg versus 0.25 ± 0.79 mg, P .001).The results of this study suggest that lidocaine patch application to the trocar site after laparoscopic appendectomy may have a positive effect on the management of postoperative pain and can eliminate the need to inject additional analgesics for further postoperative pain control.

Osteoarthritis prevalence is expected to increase markedly in the Asia-Pacific region due to rapid population aging. Identifying effective and safe therapeutic options to manage osteoarthritic pain is viewed as a priority. The Asia-Pacific Experts on Topical Analgesics Advisory Board developed consensus statements for use of topical NSAIDs in musculoskeletal pain. Evidence supporting these statements in osteoarthritic pain was reviewed. Best available evidence indicates that topical NSAIDs have a moderate effect on relief of osteoarthritic pain, comparable to that of oral NSAIDs but with a better risk-to-benefit ratio. International clinical practice guidelines recommend topical NSAIDs on par with or ahead of oral NSAIDs for pain management in patients with knee and hand osteoarthritis, and as the first-line choice in persons aged ≥75 years.

Topical analgesics are effective and alternative means to systemic therapy, often minimizing the adverse drug effects and complications of systemic analgesic use. Despite the number of available topical analgesics, there is little direction provided in practice guidelines on their appropriate use and little is known about patterns of their prescribing. To begin understanding these knowledge gaps, we sought provider perspectives on topical analgesic use at a large academic medical center. This electronic survey seeks to explore the perceptions and prescription patterns of topical analgesics among prescribers in a large academic medical center, where the availability of topical analgesics varies. Among topical analgesics, lidocaine (78%) is prescribed more frequently than nonsteroidal anti-inflammatory drugs (NSAIDs; 41%) or morphine (3%). Formulations and indications of use varied between faculty physicians and nonfaculty providers. Reasons for prescribing were largely based on anecdotal experience. Based on the survey results, it is clear that more topical agents are needed to manage pain; however, so too is guidance on appropriate prescribing.

The Cochrane Library of Systematic Reviews is published monthly online ( http://www.thecochranelibrary.com ). The library currently contains 7332 complete reviews and 2520 protocols for reviews in production. In addition, there are citations of 1,055,253 randomized controlled trials and 15,764 cited papers in the Cochrane Methodology Register. The Health Technology Assessment database contains some 17,000 citations. The impact factor of the Cochrane Library stands at 6.1. This report attempted to identify all relevant reviews published in the 2 months to May 31, 2017. Eight reviews have been identified that have potential relevance for practitioners in pain and palliative medicine. Readers are encouraged to access the full report for any articles of interest, as only a brief commentary is provided.

David Castel,1 Itai Sabbag,2 Sigal Meilin3 1The Neufeld Cardiac Research Institute, Sheba Medical Centre, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 2Lahav Research Institute, Kibutz Lahav, Negev, 3Neurology R&D Division, MD Biosciences, Nes-Ziona, Israel Abstract: Interest in the development of new topical/local drug administration for blocking pain at peripheral sites, with maximum drug activity and minimal systemic effects, is on the rise. In the review article by Kopsky and Stahl, four critical barriers in the process of research and development of topical analgesics were indicated. The active pharmaceutical ingredient (API) and the formulation are among the major challenges. The road to the development of such drugs passes through preclinical studies. These studies, if planned correctly, should serve as guidance for choosing the right API and formulation. Although rodent models for pain continue to provide valuable data on the mechanisms driving pain, their use in developing topical and localized treatment approaches is limited for technical (intraplate injection area is small) as well as mechanical reasons (non-similarity to human skin and innervation). It has been previously shown that pigs are comparable to humans in ways that make them a better choice for evaluating topical and local analgesics. The aim of this study was to summarize several experiments that used pigs for testing postoperative pain in an incisional pain model (skin incision [SI] and skin and muscle incision [SMI]). At the end of the surgery, the animals were treated with different doses of bupivacaine solution (Marcaine®), bupivacaine liposomal formulation (Exparel®) or ropivacaine solution (Naropin). Von Frey testing demonstrated a decrease in the animals’ sensitivity to mechanical stimulation expressed as an increase in the withdrawal force following local treatment. These changes reflect the clinical condition in the level as well as in the duration of the response. These data indicate a good resemblance between pig and human skin and suggest that use of these animals in the preclinical phase of developing topical analgesics can, to some extent, release the bottleneck. Keywords: postoperative pain, de-risk clinical trials, local treatment, swine&nbsp

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. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.

Mint species are widely used in traditional and conventional medicine as topical analgesics for osteoarthritic pain and for disorders of the gastrointestinal and respiratory tracts which are all associated with chronic inflammation. To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a selected group of monoterpenes especially abundant in mint species was screened by measuring bacterial lipopolysacharide (LPS)-induced nitric oxide (NO) production in murine macrophages. Nine compounds significantly decreased LPS-induced NO production by more than 30%. IC50 values were calculated showing that the order of potency is: (S)-(+)-carvone > (R)-(−)-carvone > (+)-dihydrocarveol > (S)-8-hydroxycarvotanacetone > (R)-8-hydroxycarvotanacetone > (+)-dihydrocarvone > (−)-carveol > (−)-dihydrocarveol > (S)-(-)-pulegone. Considering the carbon numbering relative to the common precursor, limonene, the presence of an oxygenated group at C6 conjugated to a double bond at C1 and an isopropenyl group and S configuration at C4 are the major chemical features relevant for activity and potency. The most potent compound, (S)-(+)-carvone, significantly decreased the expression of NOS2 and IL-1β in macrophages and in a cell model of osteoarthritis using primary human chondrocytes. (S)-(+)-carvone may be efficient in halting inflammation-related diseases, like osteoarthritis.

Background:In chronic osteoarticular pain, especially knee osteoarthritis, topical analgesics and topical non-steroidal anti-inflammatory drugs represent an interesting therapeutic alternative for patients with several comorbidities in order to avoid side effects and medical interactions.Objectives:The aim of this work was to assess how patients apply a topical analgesic.Methods:A prospective study has been conducted over a period of 4 weeks. Sixty-six patients followed for knee osteoarthritis at different stages of the disease and under topical analgesic treatment were integrated into this study. Epidemiological data, physical examination and x-ray data were collected. The impact of knee osteoarthritis was evaluated by the Lequesne and WOMAC indices. Patients were asked about how long they apply the treatment, how often they use the treatment per week and whether they are massaging the aching area while applying the treatment.Results:In the studied population, the majority of patients were women (87%) with an average age of 55 years. Forty percent of the patients were illiterate as long as 21% received a college education. Patients’ occupations were distributed as follows: 59% housewives, 21% retirees, 12% manual occupations and 8% non-manual occupations.The most common comorbidities were high blood pressure (61%), diabetes (38%) and osteoporosis (36%).The average duration of development of osteoarthritis of the knee was 9 years. The most common radiological stage was stage 1 (58%). The site was femorotibial in 88% of cases, patellofemoral in 4% of cases and bi or tri-compartmental in 8% of cases. The osteoarthritis most often affected both knees: 86% of casesThe average of the Lequesne index was 11. The average WOMAC index was 12 for pain, 1.5 for stiffness and 48 for dysfunction.All the interviewed patients were on topical analgesics for an average of 5 years.The average frequency of application of topical analgesics was 9 times per week. Housewives and retirees used the treatment on average 14 times per week while working patients use the treatment on average 5 times per week. Seventy-two percent of patients reported that they performed an average massage lasting 11 minutes with each application.Among patients with secondary and university education, 64% of patients reported that they performed a massage on the painful knee while applying the medication.Patients followed for knee osteoarthritis for more than 10 years tend to apply the local analgesic for a shorter period of time (an average of 5 minutes).Conclusion:Patients followed for osteoarthritis of the knee who are taking topical analgesics tend to make misuse, including massaging for a long time and applying treatment less frequently than recommended. The level of education does not seem to play a role in knowing the right way to apply. However, patients who have been followed for a longer period for knee osteoarthritis use the treatment more correctly.References:[1]Flores MP, Castro AP, Nascimento Jdos S. Topical analgesics. Rev Bras Anestesiol. 2012 Mar-Apr;62(2):244-52. doi: 10.1016/S0034-7094(12)70122-8. PMID: 22440379.[2]Barkin RL. The pharmacology of topical analgesics. Postgrad Med. 2013 Jul;125(4 Suppl 1):7-18. doi: 10.1080/00325481.2013.1110566911. PMID: 24547599.Disclosure of Interests:None declared.

This investigation aimed to assess the pandemic impact on the incidence of newly prescribed dermatological agents compared to the pre-pandemic period TrinetX is a real-time, federated healthcare database that was used in the retrospective review comprised of 61 million patient records at the time of the analysis This database was used to identify the incidence of newly prescribed drugs each month for two periods of the pandemic Medications were categorized by LOINC codes and categorized into groups The first period was from April-July 2020, and the second was from August-November 2020 The mean for each drug group was then compared with the pooled monthly incidence from similar periods between 2018-2019 before the pandemic Descriptive analyses were performed, and comparisons were made using a student's t-test 11 groups of dermatological agents were analyzed in both periods In the early pandemic period, 7 of 11 groups of agents showed a statistically significant reduction of up to 32 1% in prescription These agents included anti-psoriatic, anti-acne, topical anti-neoplastic, topical anti-viral, topical anti-inflammatory, topical anti-fungal, and all dermatological agents as a whole Newly prescribed topical analgesics, keratolytic, anti-perspirant, and anti-bacterial agents did not show a statistically significant decrease in prescription During the later pandemic, five of the dermatological agents showed a statistically significant decrease in prescription Anti-psoriatic, topical analgesics, topical antineoplastics, topical keratolytic, topical anti-perspirant, and topical anti-bacterial agents did not show a significant reduction This study shows that there has been a significant reduction in incidence of prescribed dermatological agents during the COVID19 pandemic Further research is needed to determine the future impact of this disruption in the dermatological care

Simple Summary The majority of dogs and cats are fearful during veterinary visits, and some individuals may show aggression as a result. We review ways to avoid negative experiences and promote positive emotions in animals visiting the veterinarian. Whenever an animal is in the practice, the veterinary team should endeavour to make the visit as pleasant as possible, by using non-threatening body language and by creating positive associations. High-value food (unless an animal needs to be fasted) or toys should be used generously throughout the visit. In the interaction with the animals, low-stress handling methods, brief pauses and adjusting the procedure based on the animal’s body language help them to feel secure. Distractions can be used to minimise perceived pain such as from injections. If a known painful area needs to be treated, pain killers are advised. For animals that are very fearful, several medication options are available that can be given prior to the veterinary visit to help them with their fears. With reward-based training, animals can learn to accept veterinary procedures. A stress-free veterinary visit benefits all involved parties—the animals, their owners, as well as the veterinary team. Abstract A high proportion of dogs and cats are fearful during veterinary visits, which in some cases may escalate into aggression. Here, we discuss factors that contribute to negative emotions in a veterinary setting and how these can be addressed. We briefly summarise the available evidence for the interventions discussed. The set-up of the waiting area (e.g., spatial dividers; elevated places for cat carriers), tailoring the examination and the treatment to the individual, considerate handling (minimal restraint when possible, avoiding leaning over or cornering animals) and offering high-value food or toys throughout the visit can promote security and, ideally, positive associations. Desensitisation and counterconditioning are highly recommended, both to prevent and address existing negative emotions. Short-term pain from injections can be minimised by using tactile and cognitive distractions and topical analgesics, which are also indicated for painful procedures such as ear cleanings. Recommendations for handling fearful animals to minimise aggressive responses are discussed. However, anxiolytics or sedation should be used whenever there is a risk of traumatising an animal or for safety reasons. Stress-reducing measures can decrease fear and stress in patients and consequently their owners, thus strengthening the relationship with the clients as well as increasing the professional satisfaction of veterinary staff.

Oral mucosa is the most common site for ulcers, and severely painful ulcers of traumatic origin prompt the patient to visit an oral physician to seek necessary treatment. Currently, numerous topical analgesics and anti-inflammatory medications are prescribed to reduce pain and accelerate healing. An alternative to this is low-level laser therapy which is a drug-free and noninvasive therapy and has shown potential results in treatment of oral ulcers. In this paper, we report a case of a patient with palatal ulcer which was successfully treated using a 660-nm (red) laser.

Background: Acute musculoskeletal pain is one of the common causes of emergency admissions. Topical analgesics are an easily tolerated option in the treatment of these pains. Objective: This study aimed to compare the efficacy of topical capsaicin and topical non-steroidal anti-inflammatory drugs in acute musculoskeletal injuries. Methods: In this prospective, randomized, controlled, double-blinded study, patients were allocated to two groups—the topical non-steroidal anti-inflammatory drug (n = 60) and topical capsaicin (n = 59). For both groups, the first dose treatment was applied as a thin layer in the emergency department to a maximum area of 5 × 5 cm. The remaining doses were administered at home by the patients for 72 h. The initial visual analog scale scores were compared with the 60th and 120th minute as well as the 24th and 72nd hour values. Differences between the visual analog scale scores, clinical response to the treatment, and side effects were evaluated. Results: The proportional reduction in visual analog scale scores for topical capsaicin was significantly higher, especially at 36 and 72 h. These rates were 0.75 (95% confidence interval: 0.77–1.42; p = 0.029) and 9.08 (95% confidence interval: 1.02–17.14; p = 0.028) at 36 h, respectively. At 72 h, they were 1.27 (95% confidence interval: 0.48–2.05; p = 0.002) and 17.07 (95% confidence interval: 8.39–25.76; p Conclusion: Topical capsaicin can be used safely in patients presenting to the emergency department with acute pain with its high analgesic efficacy and absence of systemic side effects.

Hidradenitis suppurativa (HS) is a chronic, relapsing, and painful inflammatory disease. HS patients' quality of life is severely impaired, and this impairment correlates strongly with their pain. Pain in HS can be acute or chronic and has both inflammatory and noninflammatory origins. The purpose of this review is to provide a summary of the existing literature regarding pain management in patients with HS. While there are no formal studies investigating pain management in HS, existing recommendations are based on general pain guidelines and expert opinion. Documentation of pain requires an assessment of the severity and timing of the pain. Although anti-inflammatory drugs and surgery for HS can alleviate pain, adjunctive pain medications are typically necessary. Topical analgesics, oral acetaminophen, and oral nonsteroidal anti-inflammatory drugs are considered first-line agents for the treatment of pain in patients with HS. If pain management is ineffective with those agents, oral opiates can be considered. In addition, anticonvulsants and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors possess neuropathic pain-relieving properties that offer not only control of HS-associated pain but beneficial effects on itch and depression. There is clearly a need for additional studies on pain management in patients with HS.

Pain management should be individualized for each patient as much as possible, and the use of a placebo in the clinical practice can help. The treatment with compounded topical analgesics holds a great promise for such individualized therapy, due to the fast response of patients after applying cream containing adequate concentrations of an active pharmaceutical ingredient. We present and discuss a new single-blinded placebo-controlled test paradigm, enabling the physician to quickly differentiate between responders and non-responders, and to further explore the concentration-effect response. This way the placebo assists in selecting the optimal pain treatment, and such use should be regarded as beneficial for patients and ethical correct.

In Part One of this two-part series, we discussed skin physiology and anatomy as well as generalities concerning topical analgesics. This modality of therapy has lesser side effects and drug–drug interactions, and patients tolerate this form of therapy better than many oral options. Unfortunately, this modality is not used as often as it could be in chronic pain states, such as that from neuropathic pain. Part Two discusses specific therapies, local anesthetics, and other drugs, as well as how a clinician might use specific aspects of a patient’s neuropathic pain presentation to help guide them in the selection of a topical agent.

Jeffrey A Gudin,1 Michael J Brennan,2 E Dennis Harris,3 Peter L Hurwitz,3 Derek T Dietze,4 James D Strader5 1Pain Medicine and Palliative Care, Englewood Hospital and Medical Center, Englewood, NJ, 2The Pain Center of Fairfield, Fairfield, CT, 3Clarity Science, Austin, TX, 4Metrics for Learning, LLC, Queen Creek, AZ, 5Safe Harbor Compliance and Clinical Services, LLC, Austin, TX, USA Background: Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics.Methods: This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls.Results: The unmatched intervention group (unmatched-IG) included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG). Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P

Corneal abrasions are one of the most common ocular injuries seen in the emergency department. While most patients with corneal abrasions complain of excruciating pain, permanent sequelae may develop if not managed properly. The use of topical antibiotics and other standards of treatment have greatly reduced the incidence of complications. However, there is still a lack of consensus regarding the proper management of pain in corneal abrasions. Proposed analgesics for the control of corneal abrasion pain include topical nonsteroidal anti-inflammatory drugs (NSAIDs), topical anesthetics, and topical cycloplegics. For this review, ten published randomized controlled trials were identified, focusing on the efficacy and safety of different topical analgesics used in treating corneal abrasions. Six of the trials focused on topical NSAIDs, three on topical anesthetics, and one on topical cycloplegics. There were mixed results regarding the efficacy of topical analgesics in reducing pain in patients with corneal abrasions. This review of the literature revealed that topical NSAIDs produced reductions in pain symptoms, whereas topical anesthetics and cycloplegics did not demonstrate significant improvements in either healing rates or pain control. Thus, this evidence supports the use of topical NSAIDs in the standard management of corneal abrasions. Unfortunately, the power of these studies is largely limited by small sample sizes. Larger studies must be conducted before topical analgesics can be recommended or discouraged for pain management in corneal abrasions. However, based on this review of the literature, the use of topical NSAIDs does not appear to complicate wound healing, and thus remains a safe option in patients desiring medical treatment.

Scar management using laser phototherapy continues to evolve as it gains wide acceptance among patients and providers. Despite widespread use of laser therapy, there are no guidelines or consensus published regarding optimal pre- and post-procedure patient management. Our objective is to gain insight into the best laser practices; we decided to poll colleagues nationwide. An online survey was distributed to members of the American Society of Plastic Surgeons. The survey consisted of 34 questions regarding pre- and post-procedure protocols related to laser scar therapy. Forty plastic surgeons responded to the survey. The survey demonstrated that ten types of lasers are currently used to treat scars. The most commonly used lasers are fractional Er:YAG (44.7%), pulsed dye (42.1%), and fractional CO2 (36.8%). On a Likert 3-point scale, providers favored the use of pre-procedural sunblock (2.12), topical analgesics (1.91), and oral antivirals (1.83). They also preferred the use of topical moisturizer (2.45), oral analgesics (2.29), and oral antivirals (1.97) as a part of the post-laser treatment regimen. The study verified there is no consensus regarding peri-procedure laser scar therapy regimens. As laser scar management continues to grow in popularity, this lack of consensus suggests the need for experts in the field to come together and propose agreeable protocols to be used as guidelines. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Camphor is a colorless substance available in solid and liquid form. Volatile oil form of camphor is the active ingredient of Vicks Vaporub, and Tiger Balm ointments. These ointments are commonly used as home remedies for treatment of cough, cold and for topical analgesics. They are inexpensive, over the counter remedies, hence widely used in India. Neurological complication due to camphor toxicity reported is headache, mental confusion and seizures. Here we report, a case of diffuse white matter lesions in a young female due to accidental camphor inhalation while working in factory that manufactures vicks and tiger balm. The case highlights camphor as a possible cause of toxic demyelination hence potentially exposed workers should be educated about health and safety measures to prevent such complication.

Topical analgesics applied locally to skin or to specialized compartments modify pain by actions on sensory nerve endings and/or adjacent cellular elements. With this approach, there are low systemic drug levels, good tolerability and few drug interactions, and combination with oral formulations is feasible. The goal of this review is to provide an overview of the potential for topical analgesics to contribute to improved management of neuropathic pain. Mechanistic and preclinical studies indicate much potential for development of novel topical analgesics for neuropathic pain. In humans, two topical analgesics are approved for use in post-herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8% patch), and there is evidence for efficacy in other neuropathic pain conditions. Comparative trials indicate similar efficacy between topical and oral analgesics. Not all individuals respond to topical analgesics, and there is interest in determining factors (patient factors, sensory characteristics) which might predict responsiveness to topical analgesics. There is a growing number of controlled trials and case reports of investigational agents (vasodilators, glutamate receptor antagonists, α2-adrenoreceptor agonists, antidepressants, centrally acting drugs), including combinations of several agents, indicating these produce pain relief in neuropathic pain. There is interest in compounding topical analgesics for neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of neuropathic pain.

Simple lacerations that need suture repair are a common occurrence encountered by nurse practitioners in practice. Clinicians often wonder which form of analgesia is best when repairing a minor skin laceration. Pain management during the procedure is often undertreated, allowing negative patient consequences to arise. This integrative review examines what is known about the differences of topical versus local injection of analgesia products. The review also examines the advantages and disadvantages of each application and highlights findings for nurse practitioners to make evidence-based decisions regarding laceration repair.

Steven P Stanos Rehabilitation Institute of Chicago, Center for Pain Management, Chicago, IL, USA Abstract: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events. Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, guidelines, topical analgesics, diclofenac

Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In severe cases, the most important step is stabilizing and maintaining vital functions. With some differences between species, there seems to be evidence and consensus on oral/topical analgesics, hot water and ice packs as effective painkillers and on 30 s application of domestic vinegar (4%-6% acetic acid) to prevent further discharge of unfired nematocysts remaining on the skin. Conversely, alcohol, methylated spirits and fresh water should be carefully avoided, since they could massively discharge nematocysts; pressure immobilization bandaging should also be avoided, as laboratory studies show that it stimulates additional venom discharge from nematocysts. Most treatment approaches are presently founded on relatively weak evidence; therefore, further research (especially randomized clinical trials) is strongly recommended. Dissemination of appropriate treatment modalities should be deployed to better inform and educate those at risk. Adequate signage should be placed at beaches to notify tourists of the jellyfish risk. Swimmers in risky areas should wear protective equipment. © 2013 by the authors.

OBJECTIVES Intravenous catheter placement is one of the most common sources of pain for children in inpatient settings. We sought to compare the efficacy of 2 cryotherapeutic treatments for this procedure: vapocoolant spray versus topical ice pack. METHODS We prospectively enrolled 95 patients, aged 9 to 18 years, in a pediatric emergency department who required intravenous (IV) catheters as part of their treatment. Subjects were randomly assigned to receive vapocoolant spray or topical ice pack for 3 minutes, before IV catheter placement. Subjects completed visual analog scale (VAS) scores for 3 time points: baseline, pretreatment with ice or spray, and IV insertion. The principal investigator and 2 physicians viewing video recordings of the procedure also completed VAS scores for observed pain levels. Visual analog scale scores were compared using the Wilcoxon rank sum test. RESULTS Although median VAS scores were similar, the change in VAS from baseline was of greater magnitude in the Painease group, indicating that it may be more effective. More subjects in the Painease group (76%) felt their treatment worked well, compared with 49% in the ice group. Physician-assigned VAS scores were lower and less variable than those of subjects. Most IV insertions were successful (83%). CONCLUSIONS Vapocoolant spray may be more effective than ice as an analgesic for IV insertion. Subjects were more satisfied with vapocoolant spray. Neither agent caused a decrease in successful IV insertion rates.

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. Although the literature supporting the efficacy and safety of analgesic creams (mostly compounded) is growing since the last decade, most pain physicians have not yet noticed and appreciated the therapeutic potential and clinical value of these creams. This is most probably due to a prejudice that topical application should need to act transdermally, more or less as a slow-release formulation, such as in patches delivering opioids. We will discuss this prejudice and show that there are multiple important targets in the skin to be reached by topical analgesic or anti-inflammatory compounds, and that the keratinocyte is one of those targets. By specifically targeting the keratinocyte, analgesia seems possible, effective, and safe, and thus topical analgesic creams may hold promise as a novel treatment modality for neuropathic pain.

Athletes may use topical analgesics to warm the muscles or to relieve exercise-induced aches and pains. But researchers question how much these substances actually do what athletes think they do.

Alcohol neurolysis is a well-established treatment in chronic pain management, often used in cases of intractable cancer-related pain that is refractory to other management therapies. We describe a 76-year-old woman with chronic toe neuritis who failed multiple treatments, including oral and topical analgesics, nerve blocks, and radiofrequency ablations. Alcohol neurolysis was performed via digit block of the toe resulting in 100% pain relief.

Ori Segal,1,2 Yael Segal-Trivitz,1,3 Arie Y Nemet,1,2 Noa Geffen,1,2 Ronit Nesher,1,2 Michael Mimouni4 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, 3Department of Psychiatry, Geha Psychiatric Hospital, Petah Tikva, 4Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel Purpose: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results: Overall, 66% (52/79) completed the survey. Most (98%) do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71%) usesterile surgical draping. All respondents apply topical analgesics and a majority (69%) measure the distance from the limbus to the injection site. A minority (21%) displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%). Less than half routinely assess postinjection optic nerve perfusion (44%). A majority (92%) apply prophylactic antibiotics immediately after the injection. Conclusion: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques that combine safety and efficacy while causing as little discomfort to the patients as possible. Keywords: retina, intravitreal, injection, practices, techniques, patterns

Background: Topical analgesics are important products in the armamentarium for pain relief. Methods and Findings: This study compared a topical analgesic product containing menthol to the same product with the addition of oxygenated glycerol triesters (OGTs) (also called essential oxygen oil) in 66 healthy adult subjects with acute musculoskeletal pain. Patients were randomized in a single-center, double-blind study to receive mentholated cream (MC) only or MC containing OGTs. Patients self-reported their pain intensity, lifestyle limitations, and evaluation of the mobility of the painful joint or muscle at baseline and three times daily over a seven-day course on a 100-mm visual analog scale (VAS). Patients in both groups experienced statistically significant pain relief on Day 8 over baseline, with the MC plus OGT-treated group reporting statistically significantly greater pain relief than the MC group (P = 0.016). In addition, patients treated with the combination product experienced an incremental decrease in pain during each of the 7 days of treatment in addition, and they had lower VAS scores and greater lifestyle and mobility improvements than the MC group. Both products were well tolerated with no serious adverse events reported and no signs of significant skin reactions in either group. Conclusion: Based on this study, a MC containing OGTs is safe, effective, and provided significantly better pain relief than MC alone. The combination of oxygenated glycerol trimesters and MC provided significant pain relief and offered continued improvement in pain relief over time.

This article offers conservative treatment strategies for patients suffering from musculoskeletal causes of neck pain. Basic pharmacology is reviewed, including that of opioids, nonsteroidal anti-inflammatory drugs, adjuvants, and topical analgesics. Moreover, indications for therapeutic exercise, manual therapy, and modalities are reviewed, along with any supporting literature. Treatment considerations with each category of medication and physical therapy are discussed. This article is meant to serve as a resource for physicians to tailor conservative treatment options to their individual patients.

Objectives: The aims of this study were to (i) investigate the parental beliefs about teething signs and symptoms, (ii) investigate the parents’ practices used to alleviate teething troubles and (iii) provide an educational basis for dental healthcare providers to better educate parents on this subject. Methods: A cross-sectional survey was conducted in a random sample of 1500 parents attending Maternity and Child Health Care Centers. The self-administered questionnaire contained three sections: Section I surveyed parents’ and their children’s demographic characteristics, Section II aimed to assess the general knowledge and beliefs of parents regarding their children’s teething. Section III aimed at investigating the practices that the parents would do to manage teething problems and relieve pain. The analysis of data was carried out using spss computer software. Descriptive statistics and Chi-squared test were utilized. Results: Almost 75% of the participants incorrectly attributed fever, diarrhoea and sleep disturbances to teething, and more than 50% believed systemic symptoms are not related to the process. More than 50% of the participants allowed their children to bite on chilled objects, (76.1%) used systemic analgesics and (65.6%) rubbed the gums with topical analgesics to relieve the symptoms associated with teething. Conclusions: This study shows a common lack of knowledge about teething among parents. Parents should be better educated about the teething process and the proper management of teething troubles by the dental health care providers.

One of the common complaints of nerve entrapment syndrome (NES) is neuropathic pain. Timely and effectively controlling pain is an important goal of NES treatment. Pharmacological treatment of painful NES provides noninvasive and effective pain relief, in both acute and chronic NES settings. It can be utilized as independent therapy or as an adjunct therapy along with interventional procedures or surgical treatment.

Lichen planus is a chronic mucocutaneous autoimmune disease, predominantly affects middle aged females, predisposing factors include psychological stress, drugs and various systemic conditions. A case reports of Sudanese male 32 years old. Chief complain, burning sensation in the oral cavity associated with generalized pruritis, diagnosed as lichen Planus and had been treated with systemic prednisolone, topical analgesics and chlorhexidine oral rinse. The lesions showed excellent improvement within two weeks.

Topical analgesics are in need to be differentiated from transdermal formulations of analgesics. Topical analgesics are characterized by local analgesic effects in the absence of systemic effects, and do not require a transdermal delivery formulation. There are two key issues in the development of topical analgesics. 1. For optimal clinical effects specific characteristics for the vehicle (a cream base or gel base) are required, depending on the physicochemical characteristics of the pharmaceutical active ingredient in the carrier. 2. One cannot and should not skip well designed phase II dose-finding studies, and this unfortunately happens often, as we will discuss in this paper. In fact, we will demonstrate underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. In the case of gels or creams containing ketamine, amitriptyline and baclofen, the dose-finding most probably needs to start at 10% for ketamine and amitriptyline and 2.5% for baclofen, while the doses tested were much lower: 4%, 2% and 1% respectively. Topical analgesics are promising inroads for the treatment of neuropathic pain, once sufficient attention is given to aspects such as formulation and concentration.

Ethyl chloride can be used as a cryoanalgesic, but with the availability of alternative and relatively safer topical analgesics, its use has decreased. However, it still has the advantage of being quicker to apply compared with other topical analgesics, making it ideal for use in the outpatient departments. We wanted to compare the effectiveness of ethyl chloride as an analgesic during venipuncture in children.Venipuncture was carried out using either no analgesia (NO), ethyl chloride spray (EC), or application of the topical anesthetic Ametop (TA) on children attending the phlebotomy outpatient service by experienced pediatric phlebotomists. A pain score was recorded using either the Faces scoring system or the Faces, Legs, Activity, Cry Consolability scoring system.A total of 55 patients were included in the study, 18 from group EC, 18 from group TA, and 19 from group NO. Thirteen patients from both groups EC and TA and 17 from group NO scored 2 or less on the pain scores.The use of ethyl chloride was as effective as topical anesthetics in preventing distress to children in venipuncture. However, in the appropriate situations, the use of NO could also be comfortable to the child if venipuncture was done by specialist pediatric phlebotomists.

This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are Aspirin, NSAIDs, and COX-2 inhibitors; glucosamine and chondroitin, Neurontin for pain, antidepressants for pain, and topical analgesics.

The recent recognition of the magnitude of cardiovascular risk of both nonselective nonsteroidal anti-inflammatory drugs and COX-2 selective inhibitors, in addition to the persistent concerns about the use of opioids, has brought increased attention to nonsystemic, topical analgesics. These agents have a favorable safety profile and there is increasing evidence indicating their efficacy for a variety of pain disorders. The use of topical analgesics in the treatment of the most prevalent musculoskeletal pain syndromes is described, with a focus on mechanisms for drug delivery and clinical trials data.

Topical cocaine is used by many otorhinolaryngologists because of its good local anaesthetic and vasoconstrictive properties. A review of the available literature suggests a risk/benefit analysis would suggest that in the out-patient setting local anaesthetic agents which do not contain cocaine should be used. For rhinosurgical procedures, preparations containing cocaine and adrenaline in the appropriate concentrations and doseage are safe in the vast majority of patients without previous cardiac disease. The relative benefit of using cocaine in relation to other topical analgesics and vasoconstrictors in surgery remains unproven and alternative preparations should be used wherever there is concern over the cardiac status of the patient.It is important to be alert to the possibility that patients presenting with a septal perforation or destructive midfacial lesions may be suffering from an addiction to cocaine. It is important to arrive at the correct diagnosis in a destructive process and even in the presence of raised antineutrophilic cytoplasmic antibodies (ANCA) a diagnosis of cocaine abuse should actively be excluded.