Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial
| Autor: | Wei Liu, Romà Solà, W.R. Duan, Charles Locke, Jordi Serra, Wolfram Nothaft |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Time Factors Lidocaine Adolescent medicine.drug_class Analgesic T-type Calcium Channel Blocker ABT-639 Calcium channel blocker Placebo Heterocyclic Compounds 2-Ring Young Adult Diabetic Neuropathies Double-Blind Method Reaction Time Medicine Humans Aged Pain Measurement Nerve Fibers Unmyelinated Sulfonamides business.industry Microneurography Middle Aged Calcium Channel Blockers Anesthesiology and Pain Medicine Nociception Neurology Anesthesia Neuropathic pain Female Neurology (clinical) business medicine.drug |
| Zdroj: | Pain. 156(11) |
| ISSN: | 1872-6623 |
| Popis: | T-type calcium channels are a potential novel target for treatment of neuropathic pain such as painful diabetic neuropathy. ABT-639 is a peripherally acting highly selective T-type Cav3.2 calcium channel blocker that has demonstrated analgesic efficacy in preclinical models and may have the potential to reduce spontaneous fiber activity. Microneurography is a unique technique that directly assesses the function of peripheral sensory afferents and measures abnormal spontaneous activity in single peripheral nociceptive C fibers. Abnormal spontaneous activity in C-nociceptors functions as a marker for spontaneous pain, as reduction of this activity could indicate analgesic efficacy. This randomized, double-blind controlled study evaluated the effects of a single 100-mg oral dose of ABT-639, compared with placebo, on abnormal spontaneous activity in peripheral C-nociceptors, measured for the first time by microneurography in adult patients with painful diabetic neuropathy. Lidocaine was included in this study and compared with placebo. Pharmacokinetics and safety of ABT-639 were evaluated. Thirty-nine patients were randomized, and a total of 56 analyzable C-nociceptors with spontaneous activity were identified in 34 patients. There were no significant differences in C-nociceptor activities after ABT-639 treatment vs placebo. Similar findings were observed for lidocaine vs placebo. There were no clinically significant findings in the safety of ABT-639. Further research of T-type Cav3.2 calcium channels as potential treatment targets for painful diabetic neuropathy is warranted. The utilization of microneurography as a means to measure abnormal activity in C-nociceptors in human clinical studies opens new possibilities for future studies of compounds targeting peripheral nerve hyperexcitability. ClinicalTrials.gov identifier: NCT01589432. |
| Databáze: | OpenAIRE |
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