Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy

Campbell, Claudia M.; Kipnes, Mark; Stouch, Bruce C.; Brady, Kerrie L.; Kelly, Margaret M.; Schmidt, William K.; Petersen, Karin L.; Rowbotham, Michael C.; Campbell, James N.

doi:10.1016/j.pain.2012.04.014

Cited by 152 publications

(130 citation statements)

References 37 publications

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“…Applying 0.1% clonidine gel topically on the feet reduced the level of pain in patients with PDN (98). Furthermore, clonidine along with opioid is more effective than clonidine alone to relieve pain in patients with NP (99).…”

Section: Alpha 2-adrenoceptor Agonistsmentioning

confidence: 93%

Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches

Kumar¹,

Pottabathini²,

Bhatnagar³

et al. 2016

Arch Neurosci

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Context: Neuropathic pain (NP) is a chronic debilitating painful condition with complex pathophysiology and inadequate treatment. Conventional pharmacological approaches and currently available drugs only provide marginal pain relief and cause significant adverse effects. The present manuscript is an attempt to summarize the existing data and possible pharmacological approaches available for NP.Evidence Acquisition: Information was collected from Google Scholar, Cochrane and PubMed databases, Scopus and directory of open access journals. Neuropathic pain, chronic pain, diabetic neuropathy, pathophysiology and current recommendations were the terms used to search the literature. Data from relevant animal and randomized controlled studies were selected to get the up to date information of the currently available pharmacological approaches. A note on future approaches was added based on the recent animal and human studies. Results:The current review made a significant attempt to focus on the mode of action, required dosage, advantages and the side effect profiles of currently available drugs used, or in investigational phases and their possible combinations to manage NP. Efforts are made to cover arise of NP because of diabetes and its management. At the end, authors made an attempt to cover the various therapeutic options that are currently explored for future drug development. Conclusions:The available pharmacological approaches are effective on one or other types of chronic pain. But the inadequate pain relief and limitations with each class of drugs raises the need to develop better therapeutic approaches and also understand the pathology better. The present review may be helpful to researchers intending to focus on newer therapeutic strategies and targets to manage NP.Keywords: Chronic Pain, Antidepressants, Anti-Epileptics, Opioids, Therapeutic Management ContextNeuropathic pain (NP) is a severe debilitating form of pain which originates as a consequence of lesion or disease pertaining to somatosensory system. The term lesion refers to the actual/potential damage of neurons identified via laboratory diagnostic procedure, whereas the term disease refers to the known cause for the lesion. NP is a clinical description which helps to identify the possible underlying causes. Etiology of NP ranges from traumatic nerve damage/compression, diabetes, cancer and its chemotherapy, viral infections such as HIV, alcohol and other toxin exposure, surgical amputations, etc. Furthermore, pain originated from a lesion or disease in central or peripheral somatosensory nervous system leads to the categorization of NP into central NP or peripheral NP, respectively. NP is associated with a wide range of sensory changes as described in Table 1 (1). Currently available drugs provide only marginal pain relief and are associated with various adverse effects.Therefore, understanding the current knowledge about complex pathology of NP and available drugs helps the researchers to rationalize the therapeutic approaches. This also...

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Section: Alpha 2-adrenoceptor Agonistsmentioning

confidence: 93%

Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches

Kumar¹,

Pottabathini²,

Bhatnagar³

et al. 2016

Arch Neurosci

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“…Campbell et al 22 randomized 179 patients with painful diabetic neuropathy, 89 patients to receive 0.1% topical clonidine gel and 90 to receive placebo gel, both applied 3 times per day. After 12 weeks Topical clonidine gel reduced significantly the pain in the foot of those who had sensitized C fibers (measured using topical capsaicin) in comparison with the placebo gel.…”

Section: Topical Clonidinementioning

confidence: 99%

Promising treatments for neuropathic pain

Schestatsky

Vidor

Winckler

et al. 2014

Arq. Neuro-Psiquiatr.

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In the last few years the understanding of mechanisms and, consequently, the diagnosis of neuropathic pain (NP) has becoming progressively clearer in clinical practice. However, the treatment of such condition remains challenging so far. One of the reasons for such difficulty is the diversity of mechanisms involved in NP generation and its persistency. In the present review we discuss several treatment modalities for NP that are scantily applied in daily clinical practice. For that, we collected positive clinical evidence of unusual and SECS (Safe, Easy, Cheap, and Sensible) approaches for NP. The aim of this review is not to establish the "state of the art" or rigid guidelines for NP treatment. In a different way, we only want bring new possibilities of treatment to the readers and also to motivate investigators to confirm those positive preliminary but promising results for NP reliev.Keywords: neuropathic pain, treatment, unconventional, alternative, evidence-based medicine. RESUMONos últimos anos, a compreensão dos mecanismos e consequentemente do diagnóstico da dor neuropática (DN) têm se tornado cada vez mais claros na prática clínica. Entretanto, o tratamento desta condição continua sendo um desafio. Uma das razões para tal dificuldade é diversidade de mecanismos envolvidos na geração e perpetuação da DN. Na presente revisão, os autores discutem várias modalidades de tratamento para DN pouco utilizadas na prática clínica diária. Para isso, selecionamos evidências clínicas positivas de abordagens para DN consideradas não-convencionais e do tipo "SFBR" (Seguro, Fácil, Barato e Racional). O objetivo desta revisão não é estabelecer o "estado da arte" ou diretrizes rígidas para o tratamento da DN. Diferente disso, pretendemos apenas trazer aos leitores novas possibilidades de tratamento assim como motivar pesquisadores a confirmar estes resultados preliminares, mas promissores para o alívio da DN.Palavras-chave: dor neuropática, tratamento, alternativo, medicina baseada em evidência.Neuropathic pain is defined as pain caused by lesion or dysfunction of the somatosensory system 1 and is most commonly consequence from several clinical conditions, such as diabetes, chemotherapy, herpes zoster infection, chronic alcohol abuse and other idiopathic conditions, such as idiopathic small fiber neuropathy and trigeminal pain. Patients with NP usually complain of burning and tingling sensations over the skin that almost always correspond to a plausible body distribution. Antidepressants and antiepileptic drugs are the mainstay of therapy, but they usually relieve only 40-50% of the pain 2 . Since the diagnosis of NP has becoming clearer in the last few years with the advent of new neurophysiological and histological tools, it is believed that the diversity of pathophysiological mechanism might explain the refractoriness of NP to the conventional therapeutic approaches. Therefore, several lines of investigation have been developed in parallel with the sophistication of usual drugs used in NP patients. Some of these...

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“…Although α 2A receptor agonists 10,18,58 and NO donors 1,33,63 have been used topically to alleviate chronic pain, PDE and PA inhibitors have not been previously used topically to alleviate pain. Furthermore, these agents have neither been combined systemically, nor combined in topical preparations for the treatment of chronic pain.…”

Section: Introductionmentioning

confidence: 99%

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

Ragavendran

Laferrière

Xiao

et al. 2013

The Journal of Pain

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Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α 2 -adrenergic (α 2A ) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post- CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5-10 fold leftward when combined with non-analgesic doses of α 2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α 2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain.Perspective-This article presents the synergistic anti-allodynic effects of combinations of α 2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas.

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Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy

Cited by 152 publications

References 37 publications

Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches

Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches

Promising treatments for neuropathic pain

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

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