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Neuropathic Corneal Pain: Approaches for Treatment

Neuropathic Corneal Pain: Approaches for Treatment
Publication Type
Journal Article
Research Type
Reported as
October 18, 2017
Dieckmann G, Goyal S, Hamrah P
Tufts University, University of Arkansas

Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage, and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuroregenerative and anti-inflammatory agents, and first-line systemic pharmacotherapy includes tricyclic antidepressants and an anticonvulsant. Second-line oral treatments recommended include an opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and gluten-free diet, may have additional benefits, as do potential noninvasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.

Regarding LDN, the article indicates: "Second Line Agents. Low-DoseNaltrexone (LDN). Low dose naltrexone (LDN) is an opioid antagonist for the m-opioid and k-opioid receptors. It has been shown to be an antagonist to toll-like receptor 4 that has been linked to neuropathic pain, reducing the release of pro-inflammatory cytokines and modulating microglial activity. LDN (3-5 mg) has recently been used effectively as an off label treatment in patients with chronic neuropathic pain, including fibromyalgia, complex regional pain syndrome, low-back pain, and painful diabetic neuropathy. In an RCT of 31 patients with fibromyalgia, use of LDN 4.5 mg resulted in significant decrease of pain and improved satisfaction with life as compared with placebo. Another recent paper reported a single case of successful treatment with LDN in a patient with refractory painful diabetic neuropathic pain. Common side effects include headache, tachycardia, and vivid dreams. LDN is recommended by us in NCP patients at 1.5 mg at bedtime with gradual biweekly increase of 1.5 mg to a final maximum dose of 4.5 mg taken at bedtime."