Topical clonidine for neuropathic pain.
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ABSTRACT:
SUBMITTER: Wrzosek A
PROVIDER: S-EPMC6489438 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Topical clonidine for neuropathic pain.
Wrzosek Anna A Woron Jaroslaw J Dobrogowski Jan J Jakowicka-Wordliczek Joanna J Wordliczek Jerzy J
The Cochrane database of systematic reviews 20150831
<h4>Background</h4>Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated recently in clinical trials.<h4>Objectives</h4>The objectives of t ...[more]
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Project description:BackgroundFirst-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients.Methods/designThis is a study protocol for a randomized, double-blind, placebo-controlled, phase II clinical trial with a cross-over design. It is a single-centered, 5-week study that will enroll a total of 32 patients with post-traumatic peripheral neuropathic pain. Patients will be treated topically with either a combination of clonidine and pentoxifylline or placebo for a period of 2 weeks each, in randomly assigned order across patients, with an intervening washout period of 1 week. The primary outcome measures of the study are the intensity of spontaneous pain recorded daily in a pain diary with a visual analog scale, and the degree of mechanical allodynia evoked by a brush stimulus. The secondary outcome measures of the study include scores of pain relief and change in the area of punctate hyperalgesia. This trial has been prospectively registered with ClinicalTrials.gov on November 1, 2017. ClinicalTrials.gov Identifier: NCT03342950 .DiscussionThe analgesic use of topical treatment with clonidine and pentoxifylline in combination has not been investigated in post-traumatic neuropathic pain. This study could generate the first evidence for the efficacy and safety of the formulation in alleviating pain in patients with neuropathic pain. Furthermore, this trial will provide objective grounds for the investigation of other agents that enhance tissue oxygenation in the topical treatment of peripheral neuropathic pain.Trial registrationThis trial has been registered with ClinicalTrials.gov owned by NIH's US National Library of Medicine. ClinicalTrials.gov NCT03342950 . Registered on November 1, 2017 (trial was prospectively registered).Protocol version and identifiersThis is protocol version 5, dated June 2018. McGill University Health Center (MUHC) Reaseach Ethics Board (REB) identification number: TTNP 2018-3906.
| S-EPMC7890866 | biostudies-literature
Project description:Study designReview of the literature and semi-structured interviews.ObjectiveTo explore the possible use of topical analgesics for the treatment of neuropathic pain (NP) in spinal cord injury (SCI).SettingInstitute for Neuropathic Pain, Soest, The Netherlands.MethodsA review was performed of studies on topical analgesics for SCI-related NP published up to May 2019. In addition, eight persons with SCI-related NP who were treated with topical analgesics were interviewed in a semi-structured interview on their experience with topical analgesics.ResultsSeven studies (five case reports and two case series) were found that evaluated the use of topical analgesics for SCI-related NP. None of the studies used a control treatment. Topical analgesics included baclofen, ketamine, lidocaine, capsaicin, and isosorbide dinitrate. All studies reported a decrease in NP over time. Persons interviewed were 49-72 years of age and all but one had an incomplete SCI. They used topical agents containing phenytoin, amitriptyline, baclofen, ketamine or loperamide. All showed a decrease in pain of at least 3 points on the 11-point numeric rating scale during this treatment.Discussion/conclusionsEvidence on the use of topical analgesics in SCI is scarce. Case reports, case series and interviews suggest that the use of topical analgesics can be beneficial in treating SCI-related NP. Placebo-controlled studies are required to investigate the effect of topical analgesics on SCI-related NP.
| S-EPMC7426910 | biostudies-literature
Project description:We explored whether increased C-nociceptor excitability predicts analgesic effects of topical lidocaine in 33 patients with mono- (n = 15) or poly-neuropathy (n = 18). Excitability of C-nociceptors was tested by transcutaneous electrical sinusoidal (4 Hz) and half sine wave (single 500 ms pulse) stimulation delivered to affected and non-affected sites. Analgesic effects of 24 hrs topical lidocaine were recorded. About 50% of patients reported increased pain from symptomatic skin upon continuous 4 Hz sinusoidal and about 25% upon 500 ms half sine wave stimulation. Electrically-evoked half sine wave pain correlated to their clinical pain level (r = 0.37, p < 0.05). Lidocaine-patches reduced spontaneous pain by >1-point NRS in 8 of 28 patients (p < 0.0001, ANOVA). Patients with increased pain to 2.5 sec sinusoidal stimulation at 0.2 and 0.4 mA intensity had significantly stronger analgesic effects of lidocaine and in reverse, patients with a pain reduction of >1 NRS had significantly higher pain ratings to continuous 1 min supra-threshold sinusoidal stimulation. In the assessed control skin areas of the patients, enhanced pain upon 1 min 4 Hz stimulation correlated to increased depression scores (HADS). Electrically assessed C-nociceptor excitability identified by slowly depolarizing electrical stimuli might reflect the source of neuropathic pain in some patients and can be useful for patient stratification to predict potential success of topical analgesics. Central neuronal circuitry assessment reflected by increased pain in control skin associated with higher HADS scores suggest central sensitization phenomena in a sub-population of neuropathic pain patients.
| S-EPMC9282664 | biostudies-literature
Project description:In this experiment we compare the effect of tibial nerve transection on gene expression within the dorsal root ganglion (DRG) of rats.
2014-08-01 | E-MTAB-2260 | biostudies-arrayexpress
Project description: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. Commonly used agents for topical use are amitriptyline, baclofen, ketamine and lidocaine; however, these agents do not always give the desired analgesic effect in some patients. We report for the first time a patient with chronic idiopathic axonal polyneuropathy and intractable localized neuropathic pain treated successfully with loperamide 5% cream. After application of loperamide 5% cream, the patient reported a complete reduction of pain within 30 mins, lasting for 2.5 hrs. Subsequently, the patient was able to reduce his daily intake of oxycodone, while using topical loperamide for pain relief. Loperamide is a nonprescription opioid agonist, commonly used against diarrhea. As a topical formulation, it is preferable over other opioids due to its low systemic bioavailability and low risk of crossing the blood-brain barrier. Peripheral upregulation and sensitization of opioid receptors at peripheral nerve endings and perhaps at other cell populations in the epidermis might be targets of topical loperamide.
| S-EPMC6503502 | biostudies-literature
Project description:BackgroundCritically ill newborn infants undergo a variety of painful procedures or experience a variety of painful conditions during their early life in the neonatal unit. In the critically ill paediatric and neonatal population, clonidine is prescribed as an adjunct to opioids or benzodiazepines aiming to reduce the doses of these drugs that are required for analgesia or sedation, or to facilitate weaning from mechanical ventilation. It has been shown that clonidine premedication might have a positive effect on postoperative pain in children.ObjectivesTo assess the benefit and harms of clonidine for the prevention or treatment of procedural pain; postoperative pain; or pain associated with clinical conditions in non-ventilated neonates.Search methodsWe used the standard search strategy of Cochrane Neonatal to search the CENTRAL, MEDLINE via PubMed, Embase, and CINAHL to December 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We ran an updated search from 1 January 2018 to 11 March 2020 in CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.Selection criteriaRandomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing clonidine to placebo or no treatment, opioids, paracetamol, dexmedetomidine, or non-pharmacological pain-reducing interventions for the management of procedural pain, postoperative pain, and pain associated with clinical conditions in preterm and term newborns.Data collection and analysisTwo review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, modality of administration, and dose of clonidine) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcome considered was pain: for procedural pain, the mean values of each analgesia scale assessed during the procedure and at one to two hours after the procedure; for postoperative pain and for pain associated with clinical conditions, the mean values of each analgesia scale assessed at 30 minutes, three hours, and 12 hours after the administration of the intervention. We planned to use the GRADE approach to assess the quality of evidence.Main resultsOur search strategy yielded 3383 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. We excluded three trials where clonidine was administered for spinal anaesthesia.Authors' conclusionsWe did not find any studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates.
| S-EPMC7143321 | biostudies-literature
Project description:Activation of TRPM8, a cold-sensing receptor located on the cornea and eyelid, has the potential to relieve the neuropathic ocular pain (NOP) in dry eye (DE) by inhibiting other aberrant nociceptive inputs. We aimed to investigate the effect of a topical TRPM8 agonist, cryosim-3 (C3), on relieving DE-associated NOP. We conducted a prospective pilot study of 15 patients with DE-associated NOP. These patients applied topical C3 to their eyelid, 4 times/day for 1 month. The patients underwent clinical examinations. They also completed the Ocular Pain Assessment Survey (OPAS), which is a validated questionnaire for NOP, at baseline, 1 week, and 1 month after treatment. At 1 week, the OPAS scores of eye pain intensity, quality of life (driving/watching TV, general activity, sleep, and enjoying life/relations with other people), and associated factors (burning sensation, light sensitivity, and tearing) improved. The total OPAS scores of eye pain intensity, quality of life, and associated factors remained improved at 1 month. The Schirmer test scores also improved at 1 month. TRPM8 agonist (C3) could be a novel agent for treating patients with DE-associated NOP who are unresponsive to conventional treatments.
| S-EPMC7826705 | biostudies-literature
Project description:A length-dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy). It was hypothesized that pain may arise from sensitized-hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the ?(2)-adrenergic agonist, clonidine, to the painful area. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pretibial area of each subject for 30minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n=89) or placebo gel (n=90) applied 3 times a day to their feet for 12weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0-10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo-treated group (the primary endpoint; P=0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (P<0.05). In subjects with a capsaicin pain rating ?2 (0-10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo (P=0.01). Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain.
| S-EPMC3413770 | biostudies-literature
Project description:Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.
| S-EPMC5371025 | biostudies-literature
Project description:IntroductionNumerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in keratinocytes and provide proof-of-principle data to support clinical development of topical compounded formulations for peripheral neuropathic pain syndromes, such as postherpetic neuralgia (PHN).ObjectivesThe study intended to identify objective biomarkers in PHN skin on a patient-by-patient personalized medicine platform. The totality of biopsy biomarker data can provide a tissue basis for directing individualized compounded topical preparations to optimize treatment efficacy.MethodsReferencing 5 of the most common actives used in topical pain relief formulations (ketamine, gabapentin, clonidine, baclofen, and lidocaine), and 3 well-established cutaneous mediators (ie, neuropeptides, cannabinoids, and vanilloids), comprehensive immunolabeling was used to quantify receptor biomarkers in skin biopsy samples taken from ipsilateral (pain) and contralateral (nonpain) dermatomes of patients with PHN.ResultsEpidermal keratinocyte labeling patterns were significantly different among the cohort for each biomarker, consistent with potential mechanisms of action among keratinocytes. Importantly, the total biomarker panel indicates that the enriched PHN cohort contains distinct subgroups.ConclusionThe heterogeneity of the cohort differences may explain studies that have not shown statistical group benefit from topically administered compounded therapies. Rather, the essential need for individual tissue biomarker evaluations is evident, particularly as a means to direct a more accurately targeted topical personalized medicine approach and generate positive clinical results.
| S-EPMC10876238 | biostudies-literature