ascorbic-acid and Peripheral-Nerve-Injuries

Complex regional pain syndrome (CRPS) is a heterogenous and poorly understood condition that can be provoked by quite minor injuries. The symptoms and signs of CRPS persist, long after the patient has recovered from the inciting event. In some cases, there is a clear association with a peripheral nerve injury. The degree of disability produced by CRPS is often out of proportion to the scale of the original insult and the condition is associated with protracted recovery times and frequent litigation.. We have performed a PubMed literature search, referenced landmark papers in the field and included a national expert in peripheral nerve injury and repair in our team of authors.. The diagnostic criteria for CRPS have changed repeatedly over the last two centuries and much of the historical literature is difficult to compare with more recent research. In this review article, we consider how our understanding of the condition has evolved and discuss its pathogenesis, its apparent heterogenicity and the various investigations and treatments available to the clinician.

Topics: Amputation, Surgical; Anti-Inflammatory Agents; Anticonvulsants; Antioxidants; Ascorbic Acid; Botulinum Toxins, Type A; Complex Regional Pain Syndromes; Gabapentin; Glucocorticoids; History, 20th Century; History, 21st Century; Humans; Neuromuscular Agents; Peripheral Nerve Injuries; Physical Therapy Modalities; Risk Factors; Sympathectomy

Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen-containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro. We found impaired myelination and reduced collagen expression in Sodium-dependent Vitamin C Transporter 2 heterozygous mice (SVCT2

Topics: Animals; Ascorbic Acid; Cells, Cultured; Collagen; Demethylation; Disease Models, Animal; Female; Gait Disorders, Neurologic; Ganglia, Spinal; Male; Mice; Mice, Transgenic; Peripheral Nerve Injuries; Peripheral Nerves; Remyelination; RNA, Messenger; Rotarod Performance Test; Sensory Receptor Cells; Sodium-Coupled Vitamin C Transporters; Time Factors

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

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: Animals; Ascorbic Acid; Fasting; Nerve Regeneration; Peripheral Nerve Injuries; Pyridoxine; Rabbits; Radiation Injuries, Experimental; Thiamine