ascorbic-acid and Pain--Intractable

Low-voltage-activated T-type Ca(2+) channels (T-channels), especially Cav3.2 among the three isoforms (Cav3.1, Cav3.2, and Cav3.3), are now considered to play pivotal roles in processing of pain signals. Cav3.2 T-channels are functionally modulated by extracellular substances such as hydrogen sulfide and ascorbic acid, by intracellular signaling molecules including protein kinases, and by glycosylation. Cav3.2 T-channels are abundantly expressed in both peripheral and central endings of the primary afferent neurons, regulating neuronal excitability and release of excitatory neurotransmitters such as substance P and glutamate, respectively. Functional upregulation of Cav3.2 T-channels is involved in the pathophysiology of inflammatory, neuropathic, and visceral pain. Thus, Cav3.2 T-channels are considered to serve as novel targets for development of drugs for treatment of intractable pain resistant to currently available analgesics.

Topics: Analgesics; Ascorbic Acid; Calcium Channels, T-Type; Glutamic Acid; Glycosylation; Humans; Hydrogen Sulfide; Intracellular Signaling Peptides and Proteins; Molecular Targeted Therapy; Neurons, Afferent; Pain, Intractable; Protein Isoforms; Protein Kinases; Signal Transduction; Substance P; Up-Regulation

Patients with chronic pancreatitis (CP) typically suffer intractable abdominal pain that is resistant to most analgesic strategies. Recent research indicates that the pain of CP may be in part due to oxygen free radical induced pancreatic damage. Using a randomized, double-blind, placebo-controlled crossover trial, we evaluated the efficacy of a combined antioxidant preparation in the management of CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to receive treatment with either Antox, which contains the antioxidants selenium, betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each group of patients then switched to receive the alternative treatment for a further 10 weeks. Markers of antioxidant status were measured by blood sampling, whereas quality of life and pain were assessed using the SF-36 questionnaire. Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox was associated with significant improvements in quality of life in terms of pain (+17 antioxidant vs. -7 placebo), physical (+9 vs. -3) and social functioning (+8 vs. -7), and general health perception (+10 vs. -3). We conclude that treatment with antioxidants may improve quality of life and reduce pain in patients suffering from chronic pancreatitis.

Topics: Abdominal Pain; Adult; Aged; Antioxidants; Ascorbic Acid; Attitude to Health; beta Carotene; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Methionine; Middle Aged; Pain Measurement; Pain, Intractable; Pancreatitis; Placebos; Quality of Life; Selenium; Treatment Outcome; Vitamin E