Topical Morphine Research Articles

Comparing the effect of local injection of combined morphine, triamcinolone and lidocaine and lidocaine injection on pain intensity after mastoidectomy-tympanoplasty; a triple-blind clinical trial

Introduction: Postoperative pain control is one of the patient’s rights and the challenges of surgeons and anesthesiologists since about 20% of patients experience severe pain in the first 24 hours after surgery. Mastoidectomy and tympanoplasty are common surgeries in the head and neck area, in which profound and long-term analgesia is essential. Objectives: The present study investigated the effect of the combination of topical morphine, triamcinolone, and lidocaine compared to the control group. Patients and Methods: In the current clinical trial, 68 patients’ candidates for mastoidectomy-tympanoplasty surgery were included and randomly divided into intervention and control groups. The variables of demographic, pain, hemodynamics, extubation time, and received opioids were measured. Results: The results of the current study indicated a significant reduction in the patient’s pain scores in both groups (P=0.001), while the patients of group 1 had significantly lower pain scores than group 2 after 8, 12, and 24 hours in the ward (P<0.05). Moreover, a significant reduction was observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in all patients during surgery (P<0.001). However, in patients who received morphine, triamcinolone, and lidocaine (group 1), SBP and MAP were significantly lower than group 2 after 40, 80, 100, 120, 140, and 160 minutes during surgery (P<0.05). Conclusion: The present study indicated that the combination of morphine, triamcinolone, and lidocaine compared to the control group could lead to better pain control, further reduction of SBP and MAP, reduction of post-operative opioid use, and delay during the first opioid administration. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20200825048515N39; https://irct.ir/trial/57931, ethical code; IR.MUI.MED.REC.1400.064).

MP80-03 OPIOID USE IN VETERANS WITH PROSTATE CANCER FOLLOWING SURGERY TREATMENT

You have accessJournal of UrologyCME1 Apr 2023MP80-03 OPIOID USE IN VETERANS WITH PROSTATE CANCER FOLLOWING SURGERY TREATMENT Sumedha Chhatre, S Bruce Malkowicz, Thomas Guzzo, Marilyn Schapira, and Ravishankar Jayadevappa Sumedha ChhatreSumedha Chhatre More articles by this author , S Bruce MalkowiczS Bruce Malkowicz More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , Marilyn SchapiraMarilyn Schapira More articles by this author , and Ravishankar JayadevappaRavishankar Jayadevappa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003357.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Opioid use for pain management in cancer patients is a challenge. Study objective was to determine the incidence of persistent opioid use in Veterans with early stage prostate cancer and treated with surgery. METHODS: Retrospective cohort study of Veterans diagnosed with prostate cancer between 2015 and 2016. Opioid exposure attributable to treatment was defined as the cumulative oral or topical Morphine Milligram Equivalents (MMEs) prescribed from 31 days prior to 14 days post index surgery. Outcome was any opioid use in the 13-month follow-up period. Eligibility criteria was Veterans receiving care at a VA Medical Center, aged ≥21 years, early stage prostate cancer, surgery treatment at VA Medical Center, and opioid naïve in the period 12 months to 31 days prior to index surgery. Logistic regression was used to model association between any opioid use in the follow-up period as a function of any baseline opioid use, baseline opioid use (MMEs), age, race, ethnicity, socio-economic status, dual enrollment-Medicare Part D, comorbidity, mental health conditions, chronic pain, non-opioid pain medications, cancer treatment (adjuvant chemotherapy, radiation, immunotherapy), and district. RESULTS: 2,594 Veterans with prostate cancer met our criteria. Proportion of Veterans with opioid use during the 13-moth follow-up period is shown in Table 1. The largest opioid use was observed in the first follow-up month (31.5%), and 42.5% had at least one month of opioid use in the follow-up period. Baseline opioid use (OR=5.3, 95% CI=4.1, 6.9), diagnosis year 2015 (OR=1.6, 95% CI=1.3, 1.9), Elixhauser comorbidity score of 1-3 (OR=1.9, 95% CI=1.4, 2.7), chronic pain (OR=1.4, 95% CI=1.2, 1.7), anxiety, depression or PTSD (OR=1.4, 95% CI=1.1, 1.8), and Pacific district were associated with higher risk of opioid use in the follow-up period. Dual Medicare enrollment (OR=0.73, 95% CI=0.57, 0.94), and cancer stage I (OR=0.44, 95% CI=0.30, 0.63) were associated with lower risk of opioid use in follow-up period. CONCLUSIONS: Opioid use immediately after surgery was associated with continued opioid use in the follow-up period. This has implications for optimizing pain management for Veterans with prostate cancer. Source of Funding: VA HSR&D PPO 20-121 and DoD W81XWH-19-1-0461 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1152 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sumedha Chhatre More articles by this author S Bruce Malkowicz More articles by this author Thomas Guzzo More articles by this author Marilyn Schapira More articles by this author Ravishankar Jayadevappa More articles by this author Expand All Advertisement PDF downloadLoading ...

Use of topical morphine gel in epidermolysis bullosa wounds-A series of case studies.

In recent years, the use of topical morphine gel has increased in the palliative care setting to reduce pain in chronic wounds and fungating tumours. However, there is a paucity of evidence to support its effectiveness. Epidermolysis bullosa (EB) is a rare genetic skin fragility disorder characterised by painful chronic wounds. Adequate control of wound pain can be challenging in this patient group due to other complexities associated with the more severe sub-types of the disease. Topical morphine gel has been used as an adjunct therapy in a small number of EB patients in our tertiary centre in an attempt to improve pain control and quality of life. The purpose of this paper is to demonstrate the efficacy of topical morphine gel used in a variety of EB wounds as well as patient reported reduction in pain through a series of case studies. The case studies suggest a positive effect of topical morphine gel on painful wounds across a spectrum of EB subtypes.

Clinicians' experience with topical benzydamine and morphine for the management of oral mucositis: adverse effects and barriers.

Among the evidence-based agents outlined in the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) mucositis guidelines, benzydamine and morphine are advised for the management of oral mucositis (OM) in certain cancer patients. This study is aimed to collect information from a group of highly experienced healthcare professionals in the field of oral mucositis about their clinical experience with these agents. A survey questionnaire about the clinical experience with topical benzydamine and morphine to manage oral mucositis and their related adverse effects (AEs) was electronically distributed to the members of the Mucositis Study Group of MASCC/ISOO. Eighty-eight entries were recorded (response rate 25%), and 54 entries submitted complete questionnaires about the drug-related AE (completion rate 65%) and were used for the data analysis. Of the respondents, 44% and 27.7% prescribed benzydamine and morphine to manage their patients' oral mucositis, respectively. Lack of availability in the respondent's country was the common reason for not prescribing benzydamine and morphine (18.9% and 5.4%, respectively); however, a large portion of the respondents indicated that 'another reason' stopped them from prescribing these agents (51.3% and 73%, respectively). AEs to benzydamine or morphine were observed by 25.9% and 12.9% of respondents, respectively, with mild numbness and tingling as the most common drug-related AE for both agents. The use of topical benzydamine and morphine for the management of OM varies between countries. While relatively common, the AEs related to these agents are mild. Mitigating the barriers for prescribing them may increase their use.

Efficacy and Safety of Topical Morphine: A Narrative Review.

Background. Opioids are the cornerstone of the therapy used in both acute and chronic pain syndromes to treat pain of moderate to severe intensity. The knowledge that opioid receptors also occur in other tissues outside the central nervous system has created a possibility for the topical use of opioids. Thus, local analgesia may be obtained without systemic adverse effects. Methods. A narrative review of scientific papers discussing the topical use of morphine was conducted. For this purpose, the PubMed, Google Scholar, Cochrane Library, and Mendeley databases were searched. Results. The current knowledge on topical morphine does not allow for its recommended use in everyday medical practice, but suggests it may be effective, particularly in the treatment of ulcers and erosions of inflammatory etiology and painful skin lesions including persistent post-mastectomy pain due to breast cancer. Conclusions. Topical morphine has its place beside other analgesics. An important issue is the practical possibility to meet the demand for topical formulations, which is limited by technical difficulties.

Topical Morphine Gel as a Systemic Opioid Sparing Technique

Use of topical morphine gel was explored retrospectively for treatment of painful chronic wounds in hospitalized adults. Systemic opioid use and pain intensity were characterized before and after morphine gel initiation using morphine equivalent daily dose (MEDD) and the Defense and Veterans Pain Rating Scale (DVPRS) score at 24 hours before compared to 24 hours, 48 hours, and one week after morphine gel initiation. Twenty-three patients received 371 applications of topical morphine gel. The median number of applications received was 8.0 [5.0 to 26.0] per patient. Median change in MEDD 24 hours after morphine gel initiation was 0.0 mg [−15.3 to 11.3] (n = 21), 48 hours after was −4.4 mg [−27.5 to 8.8] (n = 20), and one week after was −7.5 mg [−41.9 to −0.3] (n = 12). Median change in DVPRS score 24 hours after morphine gel initiation was 0.0 [−0.5 to 1.5] (n = 13), 48 hours after was −0.5 [−3.25 to 0.0] (n = 14), and one week after was 1.0 [−1.0 to 3.5] (n = 9). In this single-center analysis, patients with painful chronic wounds treated with morphine gel required lower doses of systemic opioids. Topical morphine gel may provide analgesia while sparing systemic opioid use.

Prevention, Evaluation, and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis

Oral mucositis is a frequent adverse effect of cancer treatment that includes radiotherapy (RT) and chemotherapy (CT). It is related to worse outcomes because of pain, nutritional problems, effects on quality of life, changes in cancer treatment, the risk of infection, and financial costs. It affects 20% to 80% of people receiving chemotherapy, and almost all patients receive head and neck radiation therapy. This review presents the current understanding and discusses evidence-based clinical management strategies for oral mucositis. The current model of mucositis pathogenesis is comprised of five broad stages. The two widely used grading systems for routine clinical care and research on mucositis are the WHO (World Health Organization) and Oral Mucositis Scale and the National Cancer Institute's Common Toxicity Criteria (NCI-CTC). The effective use of assessment scales, nonpharmacologic treatment modalities such as good professional oral hygiene, cryotherapy, and photobiomodulation, and pharmacologic therapies such as KGF-1 (palifermin) and benzydamine-containing mouthwash are important for mucositis prevention, and topical morphine is effective for the treatment of mucositis induced by radiotherapy or chemotherapy. Mucoadhesive hydrogel and anti-inflammatory medications such as celecoxib, misoprostol, and rebamipide are reported to be effective for radiation-induced mucositis. However, additional experimental studies are required to confirm the evidence.

Systematic literature review of topical local anaesthesia or analgesia to donor site wounds.

BackgroundTopical local analgesic and anaesthetic agents have been used both pre- and immediately post-harvest on split-thickness skin graft (STSG) donor site wounds (DSW). There is no systematic review of their effectiveness in providing post-harvest analgesia, or of the possible toxic effects of systemic absorption. This study is designed to address the question of which agent, if any, is favoured over the others and whether there are any safety data regarding their use.MethodsSystematic literature review of randomised controlled trials of topical agents applied to STSG DSWs, with a view to providing analgesia. Studies identified via search of Cochrane and EBSCO databases. No restrictions on language or publication year. Primary outcomes: pain at the time of (awake) STSG, and post-harvest pain (up to first dressing change). Secondary outcome was serum medication levels relative to published data on toxic doses. Cochrane risk of bias assessment tool utilised in assessment of included studies. At least 2 reviewers screened and reviewed included studies. A narrative review is presented.ResultsThere were 11 studies meeting inclusion criteria. Overall methodological quality and patient numbers were low. Topical eutectic mixture of lidocaine and prilocaine pre-harvest affords good local anaesthesia in awake STSG harvesting. Topical bupivacaine (5 studies) or lidocaine (1 study) gave significantly better post-harvest anaesthesia/analgesia than placebo. Topical morphine performs no better than placebo. Topical local anaesthetic agents at reported doses were all well below toxic serum levels.ConclusionsTopical local anaesthetics (lidocaine or bupivacaine) provide good analgesia, both during and after STSG harvest, at well below toxic serum levels, but there are no good data determining the best local anaesthetic agent to use. There is no evidence morphine performs better than placebo.

Topical opioid use in dermatologic disease: A systematic review.

Topical opioid formulations offer a potential solution to manage pain and decrease the use of systemic opioids. Synthesis of use and efficacy of topical opioids in dermatological conditions has not been well characterized. We conducted a systematic search of the PubMed, Embase, and Cochrane databases from 1980 to February 2021. This study analyzed data from 14 articles and 263 patients on the use of topical opioids for pain related to chronic ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts. Topical opioids included in this review were topical morphine and diamorphine. Common formulations consisted of 0.2-10mg of opioid compounded with hydrogel or IntraSite gel. Topical opioids were variably effective in the use for pain control related to chronic ulcers and other dermatologic conditions. For example, the use of topical opioids appears to be effective in the reduction of pain related to pressure ulcers. Topical opioids were generally well tolerated. Insufficient data exist to adequately evaluate the efficacy and safety of topical opioid use in the context of nonpressure ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts.

Morphine Versus Loperamide with Intrasite Gel in the Treatment of Painful Dermal Ulcers: A Randomized, Crossover Study

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application. OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel. STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups – group morphine or group loperamide – for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day. SETTING: Medical college and hospital. METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups. RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group. LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa. CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects. KEY WORDS: Loperamide, morphine, painful ulcer

Evaluation of topical morphine for treatment of oral mucositis in cancer patients.

Oral mucositis is a painful side effect to chemotherapy. Orally applied opioids may offer analgesia with fewer side effects than systemic opioids. A randomized trial comparing the analgesic effect of a morphine oromucosal solution (OM) to placebo and a positive control group receiving intravenous (IV) morphine as an add-on treatment to morphine patient-controlled analgesia (PCA) in a mixed population of paediatric and adult haematology patients. All patients in the study were equipped with a morphine PCA pump and the participating patients were instructed to use this pump as an escape. Primary outcome was morphine consumption (mg/kg/hour) on the PCA pump. Secondary outcomes included pain intensity difference at rest and when performing oral hygiene, time to first PCA bolus, nutrition intake and adverse events. A total of 60 patients (38 children <18 years) were randomized. Thirty patients were allocated to morphine OM/placebo IV (group MO), 15 patients to placebo OM/morphine IV (group MI) and 15 patients to placebo OM/placebo IV (group P). The median morphine consumption in the MO group (22.7 mcg/kg/hour 95% confidence interval (CI) 19.4-29.4 mcg/kg/hour, p = 0.38) was not significantly different from the placebo group (24.6 mcg/kg/hour 95% CI 16.8-34.4 mcg/kg/hour, p = 0.44) or the MI group (13.7 mcg/kg/hour 95% CI 9.7-37.8 mcg/kg/hour). For the secondary outcomes, the analysis of summed pain intensity difference after the first, third and fourth administrations of study medication indicated a reduction in pain for the MI group compared to the P and MO groups. No serious adverse events were reported. The findings indicate that the analgesic effect of peripherally applied morphine is not significantly different from placebo, and parenteral opioids should continue to be the standard of care.

Analgesic effect of topical and subconjunctival morphine in dogs after phacoemulsification: A pilot study.

To determine the efficacy of a single treatment of topical and subconjunctival 0.1% preservative-free morphine sulfate (PFMS) in providing analgesia following phacoemulsification in dogs. Ten diabetic and ten non-diabetic client-owned dogs treated with bilateral phacoemulsification. A prospective, randomized, masked, negative-controlled clinical trial was performed. All dogs received topical (0.2mL) and subconjunctival (0.1mL) 0.1% PFMS in one eye following phacoemulsification. The other eye received an equal volume and mode of administration of balanced salt solution (BSS). Ophthalmic examination, blinking rates, tearing, conjunctival hyperemia, aqueous flare, and central corneal esthesiometry (CCE) were evaluated in all eyes 1day prior to surgery and at 4, 24, and 48hours after surgery. Complete physical examination, ocular ultrasound, electroretinogram, hemogram, and serum biochemistry panel were performed in all dogs prior to phacoemulsification. All dogs received the standard of care treatment before and after surgery, including uniform anesthetic protocol. Baseline ophthalmic exams were unremarkable, except for the presence of cataracts, in all dogs. The mean CCE (±SD) at 4hours post-operatively was 1.76±1.27g/mm2 and 1.85±1.5g/mm2 for the negative control and PFMS groups, respectively. There were no statistical differences in blepharospasm, conjunctival hyperemia, tearing, aqueous flare, blinking rates, CCE, or intraocular pressure (IOP) between the treatment groups for any of the time points for the non-diabetic and diabetic dogs, or for all dogs combined (P>.05). Topical and subconjunctival 0.1% PFMS did not affect the evaluated parameters after phacoemulsification in the study dogs at the timepoints assessed.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients and clinical practice guidelines.

To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM). A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible. Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain.

Development of a sterile morphine hydrogel for the local treatment of painful skin ulcers

ObjectivesIt is often difficult to relieve the pain from skin ulcers. In several patients, topical morphine, applied as a hydrogel, has been described as useful. There is no such product...

Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye.

To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. Six healthy horses. Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia. Morphine quantification in serum, aqueous, and vitreous humor was performed by ELISA. Treated and control corneas were submitted for histopathology. Horses were monitored for adverse ocular and systemic effects throughout the study period. All horses developed mild mucoid ocular discharge in the treated eye. One horse developed a fever during treatment. Morphine was detected in the aqueous humor of the treated eye for all horses with mean ± standard deviation of 165.18 ng/mL ± 87.69 ng/mL. Morphine was detected in vitreous humor of the treated eye of 5 of 6 horses with mean ± standard deviation of 4.87 ± 4.46 ng/mL. Morphine was detected in the serum of 5 of 6 horses at varying time points. Maximum systemic concentration reached in a single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in microscopic appearance between morphine-treated and control corneas. Topical administration of 1.0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects. Topical ophthalmic morphine application resulted in both ocular and systemic absorption.

Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial.

IntroductionPainful mucosal and cutaneous lesions are often less responsive or even refractory to systemic opioid analgesics. There is evidence suggesting that the effectiveness of topical morphine be restricted to inflammatory pain. The studied groups were small and the observation period relatively short. The aim of this study was to assess the effectiveness and safety of topical morphine for pain related to mucosal lesions and skin ulcers.Material and methodsThe study was a 14-day randomized placebo-controlled cross-over trial (RCT) with a 28-day follow-up open phase (OP). The trial was conducted in adult patients with localized cancer-related pain and treated with systemic opioids in an oncology center or home hospice. The patients administered 0.2% gel on the mucosal lesion or 0.2% ointment on the skin lesion by themselves, without restrictions regarding the number of doses per day. The primary measurements were mean pain intensity (MPI) and mean pain relief (MPR) on the numeric rating scale (NRS 0–10), and ITT analysis was performed.ResultsThirty-five patients were randomized to the RCT, and all of them completed 14-day observation. The MPI before the treatment was NRS 5.9 and decreased to 2.5 after morphine (p < 0.0001 vs. placebo). The MPR was 57% after morphine, and 77% of the patients using topical morphine obtained clinically significant (at least 50% of the starting value) pain relief, statistically different from placebo. The analgesic effect was sustained over the 28-day OP period (p = 0.00001). There were only 2 cases of moderate pruritus, and no other side effects were reported.ConclusionsTopical morphine was found to be a fast acting, highly effective, and safe medication for mucosal and skin lesions in palliative patients, with a sustainable pain relief effect over the 28-day observation period.

Opioids and opioid receptors orchestrate wound repair

We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS-treated MOPr-KO mice compared with reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin. We next examined whether neuropeptide expression was involved in the mechanism of MOPr-mediated wound closure. Substance P (SP) and calcitonin gene-related peptide immunoreactivity (ir) was significantly increased in the skin of MOPr-KO mice as compared with WT mice. Neuropeptide-ir was increased significantly in PBS-treated wounds of MOPr and WT mice, but morphine treatment reduced neuropeptide immunoreactivity in both as compared with PBS. Wounding of keratinocytes led to the release of opioid peptide beta-endorphin (β-END) in conditioned medium, which stimulated the proliferation of endothelial cells. MOPr-selective (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, CTOP) and nonselective OPr antagonist naloxone-inhibited endothelial proliferation induced by wounded keratinocyte-conditioned medium. In addition, accelerated wound area closure invitro by morphine was suppressed by methylnaltrexone, a nonselective OPr antagonist with high affinity for MOPr. Morphine and its congeners stimulated the proliferation of endothelial cells from WT mice but not those from MOPr-KO mice. Furthermore, morphine-induced mitogen-activated protein kinase/extracellular signal-regulated kinase phosphorylation in endothelial cells was significantly decreased in MOPr-KO mice as compared with WT mice. Collectively, these data suggest that MOPr plays a critical role in the proliferation phase with the formation of granulation tissue during wound healing.

Effect of Topical Morphine on Cutaneous Leishmaniasis in an Animal Model: A Preliminary Report.

BackgroundPentavalent antimonials remain the choice of treatment for leishmaniasis, despite their toxicity, high cost, and difficult administration. As an alternative, morphine may induce the healing process of cutaneous leishmaniasis by its immunoregulatory characteristics.ObjectivesTo study the effect of morphine on the wound-healing process of cutaneous leishmaniasis (CL) in a mouse model.Materials and MethodsThis was an experimental study in which 40 BALB/c mice (female, 6 - 8 weeks) were divided into four groups (each n = 10) who received either placebo alone (group 1), morphine ointment after parasite inoculation (group 2), morphine ointment after wound occurrence (group 3), or placebo after wound occurrence (group 4). Wound size was measured weekly for eight weeks.ResultsOn the first day of treatment, the lesions measured ~1.5 mm in diameter. After eight weeks of treatment, the wound size was significantly smaller in the mice who received morphine ointment (4.81 ± 3.22 mm) compared to those who received placebo after parasite inoculation (8.95 ± 5.71 mm; P = 0.0001) or placebo after wound occurrence (P = 0.028).ConclusionsThe above data suggest that topical application of morphine accelerates the healing process of CL wounds. We are cautiously optimistic that the results of this study can be used clinically for potentiating CL wound-healing.

Wound Healing Society 2014 update on guidelines for arterial ulcers.

Wound Healing Society 2014 update on guidelines for arterial ulcers.

Evaluating topical opioid gel on donor site pain: A small randomised double blind controlled trial

BackgroundAutologous donor skin harvested for transplantation is a common procedure in patients with burns, and patients often feel more pain at the donor site than is justified by the extent of trauma. Topical morphine gels have been thought to have an effect on peripheral opioid receptors by creating antinociceptive and anti-inflammatory effects, which could potentially reduce the systemic use of morphine-like substances and their adverse effects. MethodsWe therefore did a paired, randomised, double-blind placebo study to investigate the effect of morphine gel and placebo on dual donor sites that had been harvested in 13 patients. Pain was measured on a visual analogue scale (VAS) 15 times in a total of 5 days. ResultsThe mean (SD) VAS was 1.6 (2.3) for all sites, 1.5 (2.2) for morphine, and 2.0 (2.5) for placebo. The pain relieving effects of morphine gel were not significantly better than placebo. ConclusionThe assessment of pain at donor sites is subjective, and more systematic and objective studies are needed.