[show abstract][hide abstract] ABSTRACT: Voltage-gated calcium channels (VGCC) play obligatory roles in diverse physiological functions. Pathological conditions leading to changes in their biophysical properties and expression levels may cause malfunctions of VGCC-mediated activities, resulting in disease states. It is believed that changes in VGCC properties under pain-inducing conditions may play a causal role in the development of chronic pain, including nerve injury-induced pain or neuropathic pain. For the past several decades, preclinical and clinical research in developing VGCC blockers or modulators for chronic pain management has been fruitful, leading to some U.S. Food and Drug Administration-approved drugs currently available for chronic pain management. However, their efficacy in pain relief is limited in some patients, and their long-term use is limited by their side-effect profiles. Certainly, there is room for improvement in developing more subtype-specific VGCC blockers or modulators for chronic pain conditions. In this review, we summarized the most recent preclinical and clinical studies related to chronic pain medications acting on the VGCC. We also included clinical trials aiming to expand the application of approved VGCC drugs to different pain states derived from various pathological conditions, as well as drug combination therapies trying to improve the efficacies and side-effect profiles of current pain medications.
Journal of the American Society for Experimental NeuroTherapeutics 10/2009; 6(4):679-92. · 5.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ziconotide is a conopeptide intrathecal (IT) analgesic which is approved by the US Food and Drug Administration (FDA) for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness), dizziness or lightheadedness, weakness, visual problems (eg, double vision), elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverse effects. Subsequently, clinicians have gained appreciation for ziconotide's relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.
Therapeutics and Clinical Risk Management 07/2009; 5(3):521-34.
[show abstract][hide abstract] ABSTRACT: Lower-limb edema is recognized as an untoward side effect of intrathecal opioid therapy. Cellulitis, an acute, spreading pyogenic inflammation of the dermis and subcutaneous tissue, predisposed by persistent leg edema, can become problematic in patients on intraspinal opioid infusion therapy.
To present a case of recurrent cellulitis in an elderly lady with persistent leg edema associated with intrathecal morphine/hydromorphone infusion therapy.
Sixty-one-year-old woman with intractable chronic low back pain and bilateral leg pain treated with an intrathecal infusion of morphine up to 5 mg/day over 3 months with satisfactory pain control developed progressive lower extremity edema, complicated by recurrent cellulitis, requiring repeated hospitalization and intravenous antibiotic treatment. Switching to intrathecal hydromorphone helped minimally. Intrathecal baclofen and clonidine infusion resulted in complete resolution of leg edema and pain relief over the following 12 months.
Intrathecal Baclofen and Clonidine may be used as alternatives to provide spinally mediated antinociception when intraspinal opioid fails due to pharmacological side effects such as persistent edema.
Pain Medicine 04/2010; 11(6):972-6. · 2.46 Impact Factor
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