Nonopioid Analgesic Agents

The Peripheral Neuropathy Solution

Peripheral Neuropathy Program By Dr. Randall Labrum

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Another relatively recent addition to pain therapy armamentarium is tramadol (Ultram(R); Ortho-McNeil-Janssen, Titusville, NJ), a centrally acting, synthetic, non-narcotic analgesic that has been available in the United States since 1995. Its two mechanisms of action are (1) low-affinity binding to mu opioid receptors and (2) weak inhibition of norepinephrine and serotonin reuptake. Tramadol is, therefore, a weak opioid agonist and mimics some of the properties of tricyclic antidepressants (TCAs). A recent double-blind, randomized, placebo-controlled trail in patients with painful diabetic neuropathy found that those receiving an average dose of 210 mg/day of tramadol had significant pain relief with better physical and social functioning compared with patients receiving placebo (Finnerup et al. 2005). Most frequently occurring side effects were headache, constipation, nausea, and somnolence.

Topical Agents

Topical analgesics for neuropathic pain are attractive treatment options because they deliver medication locally and are usually well tolerated. Topical lidocaine (5%) is a peripherally acting topical analgesic that exerts its effect by transdermally delivering small amounts of lidocaine sufficient to block sodium channels on small pain fibers but insufficient to interfere with normal conduction of larger sensory fibers. When applied to a painful area, it produces local analgesia, with minimal systemic absorption and, therefore, minimum risk of systemic side effects or drug-drug interactions. In double-blind randomized controlled studies the lidoderm patch was evaluated as an adjunctive add-on medication for the treatment of chronic peripheral neuropathic pain syndromes from various causes and found to be effective in reducing both ongoing pain and allodynia (Meier et al. 2003).

In addition to the FDA-approved 5% lidocaine patch, other topical treatments include capsaicin, a vanilloid compound isolated from chili peppers that is available in formulations that do not require a prescription. It is believed to elevate pain threshold through depletion of substance P from the membranes of c-nociceptive fibers and through induction of calcitonin gene-related peptide.

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