ascorbic-acid and Neuralgia

Neuropathic pain is a chronic pain condition, which is resistant to therapy. Ascorbate was released because of the activation of glutaminergic neurons. Due to the important role of N-methyl-D-aspartate (NMDA) receptors in the pathophysiology of neuropathic pain, this study investigated the analgesic efficacy of ascorbic acid (AA) in neuropathic pain condition and the role of NMDA receptors in this effect.. For this purpose, adult male rats were randomly allocated to experimental groups (n=8 in each group). Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. During the second week after CCI, animals received a single injection of 1, 3, 5, or 10 mg/kg of AA intraperitoneally and pain threshold was determined 15 and 60 min later. The antinociceptive effect of chronic administration was also evaluated by intraperitoneal injection (IP) of 3 mg/kg AA for 3 weeks. To determine the role of NMDA receptors, separate groups of animals 30 min after single injection of AA (1 mg/kg) animals received i.p. injection of ketamine (5 mg/kg), MK-801 (0.01 mg/kg), or glutamate (1000 nmol) and were tested 20 min afterwards. Data analyzed by ANOVA and Newman-Keuls tests and p<0.05 were considered as significant.. IP of 3, 5 and 10 mg/kg increased the pain threshold during the second week after CCI (p<0.05, F=3 in tactile allodynia and p<0.01, F=3.2 in thermal and mechanical hyperalgeisa). Chronic administration of AA also produced antinociceptive effect. Ascorbic acid (1 mg/kg, i.p.) inhibited MK-801 and ketamine-induced antinociception response significantly (p<0.001, F=2). It also prevented the analgesic effect of glutamate administration (p<0.001, F=2).. The results indicated that AA produced a dose-dependent antinociceptive effect that seems to mediate through its interaction with NMDA receptors.

Topics: Analgesics; Animals; Ascorbic Acid; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Ketamine; Ligation; Male; Neuralgia; Pain Threshold; Peripheral Nerve Injuries; Rats; Receptors, N-Methyl-D-Aspartate; Sciatic Nerve

N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been associated partly with its antioxidant properties. However, the effect of NAC on the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic acid (a key antioxidant molecule of nervous tissue) and total antioxidant capacity (TAC) is unknown. Thus, our study assessed these parameters in the lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve, one of the most commonly employed animal models of neuropathic pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve). All rats received intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7 days after surgery. NAC treatment prevented the CCI-induced increase in lipid hydroperoxide levels only at day 1, although the amount was higher than that found in naive rats. NAC treatment also prevented the CCI-induced increase in ascorbic acid content, which occurred at days 1, 3, and 7. No significant change was found in TAC with NAC treatment. The changes observed here may be related to the antinociceptive effect of NAC because modulation of oxidative-stress parameters seemed to help normalize the spinal cord oxidative status altered by pain.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Constriction; Free Radical Scavengers; Lipid Peroxides; Male; Neuralgia; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Reproducibility of Results; Sciatic Neuropathy; Spinal Cord; Time Factors; Treatment Outcome

Gabapentin (Gap) relieves neuropathic pain, but it has several adverse effects as well. We aimed to investigate whether vitamin C (VitC) supplementation would reduce the effective dose of Gap for analgesia in rats with chronic constriction injury (CCI).. Rats were randomly assigned to Sham, CCI, VitC, Gap, and VitC+Gap treatment groups. CCI, involving the left sciatic nerve, was induced in all animals except the Sham group. VitC (500mg/kg (body weight)), Gap (10, 30, or 100mg/kg), or VitC (500mg/kg)+Gap (10, 30, or 100mg/kg) were injected intraperitoneally twice daily for a week from 7days after sham or CCI surgery. Mechanical paw withdrawal threshold (PWT), thermal paw withdrawal latency (PWL) and malondialdehyde (MDA) content in serum or spinal cord tissues were all measured. The expression of sodium dependent vitamin C transporter 2 (SVCT2) and glucose transporter 3 (GLUT3) in dorsal root ganglion (DRG) were detected by quantitative real-time PCR, Western blot and immunohistochemistry.. No more than 30mg/kg Gap could restore the decrease of PWT or PWL induced by CCI so long as combined with 500mg/kg VitC. For mechanism study, we found that VitC supplementation would remarkedly ameliorate oxidative stress in peripheral blood, and possibly cause a positive feedback in VitC uptake of neurons in DRG by promoting SVCT2 expression.. Vitamin C can enhance gabapentin's analgesic effect. And the underlying mechanism may be concerned with antioxidative responses which were more obvious in peripheral blood than in the neurons.

Topics: Amines; Analgesics; Animals; Ascorbic Acid; Cyclohexanecarboxylic Acids; Drug Synergism; Gabapentin; gamma-Aminobutyric Acid; Male; Neuralgia; Oxidative Stress; Rats; Rats, Sprague-Dawley

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Calcium Channels, T-Type; Dinoprostone; Humans; Hydrogen Sulfide; Molecular Targeted Therapy; Neuralgia; Paclitaxel; Peripheral Nervous System Diseases

Ca(v) 3.2 T-type calcium channels, targeted by H(2) S, are involved in neuropathic hyperalgesia in rats and ascorbic acid inhibits Ca(v) 3.2 channels. Therefore, we evaluated the effects of intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbate derivative on hyperalgesia induced by NaHS, an H(2) S donor, and on neuropathic hyperalgesia.. In rats mechanical hyperalgesia was evoked by i.pl. NaHS, and neuropathic hyperalgesia was induced by L5 spinal nerve cutting (L5SNC) or by repeated administration of paclitaxel, an anti-cancer drug. Dermal ascorbic acid levels were determined colorimetrically.. The NaHS-evoked Ca(v) 3.2 channel-dependent hyperalgesia was inhibited by co-administered ascorbic acid. Topical application of DI-VCP, but not ascorbic acid, prevented the NaHS-evoked hyperalgesia, and also increased dermal ascorbic acid levels. Neuropathic hyperalgesia induced by L5SNC or paclitaxel was reversed by i.pl. NNC 55-0396, a selective T-type calcium channel blocker, ascorbic acid or DI-VCP, and by topical DI-VCP, but not by topical ascorbic acid. The effects of i.pl. ascorbic acid and topical DI-VCP in the paclitaxel-treated rats were characterized by the faster onset and greater magnitude, compared with their effects in the L5SNC rats. Dermal ascorbic acid levels in the hindpaw significantly decreased after paclitaxel treatment, but not L5SNC, which was reversed by topical DI-VCP.. Ascorbic acid, known to inhibit Ca(v) 3.2 channels, suppressed neuropathic hyperalgesia. DI-VCP ointment for topical application may be of benefit in the treatment of neuropathic pain.

Topics: Administration, Topical; Animals; Ascorbic Acid; Calcium Channel Blockers; Calcium Channels, R-Type; Cation Transport Proteins; Disease Models, Animal; Hyperalgesia; Male; Neuralgia; Ointments; Pain Threshold; Patch-Clamp Techniques; Rats; Rats, Wistar; Sensory Receptor Cells; Skin; Skin Absorption

Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.

Topics: Analgesics; Animals; Ascorbic Acid; Behavior, Animal; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Freund's Adjuvant; Ganglia, Spinal; Hyperalgesia; Inflammation; Injections, Spinal; Male; Mice; Mice, Inbred C57BL; Neuralgia; p38 Mitogen-Activated Protein Kinases; Peripheral Nerve Injuries; Phosphorylation; Reactive Oxygen Species; Spinal Cord; Time Factors; Vitamin E

Topics: Adult; Aged; Arthritis, Rheumatoid; Ascorbic Acid; Drug Synergism; Female; Humans; Male; Middle Aged; Muscular Diseases; Neuralgia; Pain; Salicylamides; Spinal Diseases; Surveys and Questionnaires; Triamcinolone

Topics: Adolescent; Adult; Aged; Anemia; Ascorbic Acid; Cachexia; Child; Female; Herpes Zoster; Humans; Liver Diseases; Male; Middle Aged; Neuralgia; Neuritis; Vascular Diseases; Vitamin B Complex

Topics: Ascorbic Acid; Neuralgia; Rheumatic Diseases; Salicylates; Succinates; Vitamins