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Free PDF Download Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2014; 18: 2766-2771 Peripheral neuropathy in obstetrics: efficacy and safety of α-lipoic acid supplementation M. COSTANTINO, C. GUARALDI 1, D. COSTANTINO 2, S. DE GRAZIA 3, V. UNFER 3 Chemistry and Pharmaceutical Technologies, University of Ferrara, Ferrara, Italy 1Obstetrics and Gynaecology Unit, Ospedale di Valdagno (VI), Italy 2Female Health Centre, Azienda USL, Ferrara, Italy 3A.G.UN.CO. Ostetric and Gynecological Center, Rome, Italy Abstract. – OBJECTIVE : Neuropathic pain more prone to the development of neuropathic during pregnancy is a common condition due to syndromes. First and foremost, the physical the physical changes and compression around changes caused by the enlargement of the uterus pregnancy and childbirth that make pregnant women more prone to develop several medical and the development of the foetus cause postural conditions such as carpal tunnel syndrome, sci - changes and nutation of the pelvic girdle that fa - atica, meralgia paraesthetica and other nerve en - cilitate the development of low back pain and en - trapment syndromes. Most of the treatments trapment neuropathies. The mutation of the usually performed to counteract neuropathic pelvic girdle is favoured during pregnancy also pain are contraindicated in pregnancy so that, by the presence of high concentrations of relaxin, the management of these highly invalidating conditions remains an issue in the clinical prac - which is produced from the tenth week of gesta - tice. We aimed to review the efficacy and safety tion and causes a laxity in the joints not only in of alpha lipoic acid supplementation in the treat - the pelvis, but also on a vertebral level, which ment of neuropathic pain. makes pregnant women more prone to low back DISCUSSION: Lipoic acid is a co-factor essen - pain, sciatica and pelvic pain. tial in the regulation of mitochondrial energy. It The data available in literature suggest there is has been demonstrated that lipoic acid supple - mentation is involved in several biochemical a close relationship between low back or pelvic processes and actions, exerting important an - pain during and after pregnancy and physically tioxidant and anti-inflammatory activity and sig - demanding jobs, the presence of low back pain nificantly improving pain and paraesthesia in pa - before pregnancy and pelvic pain during preg - tients with sciatica, carpal tunnel syndrome and nancy. On the other hand, there would not appear diabetic neuropathy. to be any significant relationship with weight CONCLUSIONS: Efficacy of lipoic acid is com - 1 bined with a high safety profile, making this mol - gain during pregnancy . ecule a novel candidate for the management of Most of the analgesic medications usually several diseases. Data reported so far are used to treat neuropathic pain are contraindicated promising and dietary supplementation with in pregnancy, as is surgery to resolve the nerve lipoic acid seems a useful tool to contrast neuro - impingement. The best approach to these often pathic pain during pregnancy. highly invalidating conditions during pregnancy, Key Words: therefore, remains a matter for debate. Neuropathic pain, Nerve entrapment syndromes, To restrict the administration of potentially Pregnancy, Lipoic acid . dangerous medication, it is appropriate to inter - vene with rehabilitation therapies and consider administration of neuroprotectors, which are not Introduction contraindicated during pregnancy and have been seen to be efficacious in the treatment of pain Neuropathic pain is common during pregnan - and paraesthesia in peripheral neuropathies 2. cy . Pregnant women are particularly prone to the Alpha-lipoic acid (ALA), also known as thioc - development of neuropathies such as carpal tun - tic acid, and its reduced form, dihydrolipoic acid nel syndrome, sciatica, meralgia paraesthetica (DHLA) are naturally occurring compounds with and other nerve entrapment syndromes. There are one chiral centre (Figure 1). The R form is the a number of factors that make pregnant women only enantiomer synthetized and used in the bio - 2766 Corresponding Author: Demetrio Costantino, MD; e-mail: [email protected] Peripheral neuropathy in obstetrics: efficacy and safety of α-lipoic acid supplementation IκB, a protein that inhibits NF- κB, and in direct - ly reducing the expression of NF- κB and of MMP-9s (matrix metalloproteinase-9), an en - α-Lipoic Acid (ALA) Oxidized zyme responsible for the degradation of the ex - tracellular matrix 5. On the basis of these mechanisms, ALA sup - plementation has been seen to exert important antioxidant and anti-inflammatory activity and to Dihydrolipoic acid (DHLA) significantly improve pain and paraesthesia in Reduced patients with sciatica, carpal tunnel syndrome and diabetic neuropathy 6-9 . Figure 1. The oxidized and reduced forms of lipoic acid. Low Back Pain and Sciatica Epidemiological studies have shown that 49- logical system as a co-factor essential to α-ke - 56% of pregnant women suffer from low back toacid dehydrogenase activity, playing a funda - pain; in most cases the pain appears between the mental role in regulating mitochondrial energy 5th and 7 th month of pregnancy. Another interest - metabolism. In addition to being synthesised in - ing fact is that the pain often does not disappear side the body, ALA can also be taken in through after childbirth, rather it tends to become chronic. food or dietary supplements and it has been ob - The causes of low back pain include the in - served that, following absorption, it is involved in crease in the biomechanical load that alters the a number of biochemical processes and actions, normal load balances on the spine and the in - rather than being used as a co-factor 3. crease in the laxity of the collagen tissue, due to Several studies indicate that the intake of ALA the action of relaxin, which acts above all on the supplements provides various therapeutic op - sacroiliac joint and on the pubic symphysis, but tions, given its potent antioxidant and detoxify - may also affect the spine, causing articular prob - ing actions, which help to overcome cardiovascu - lems also in the lumbar region. lar, cognitive and neuromuscular deficits and In some cases, simple low back pain can be as - modulate various inflammatory pathways. ALA sociated with a radicular syndrome, sciatica. Sci - inhibits the production of vascular and intracellu - atica is a form of peripheral neuropathy charac - lar adhesion molecules (VCAM-1 and ICAM-1), terised by pain in the lumbar and lumbosacral reduces the expression of CD4 on the surface of spine that irradiates to the lower limb in the sciat - blood mononuclear cells, reduces the secretion of ic nerve territory. Sciatica is the most common tumour necrosis factor (TNF)- α and inhibits the cause of neuropathic pain. The involvement of activation and cytotoxicity of natural killer (NK) the sciatic nerve, due to the impingement of the cells 4. In addition, given inflammation’s oxida - sensory nerve roots in the intervertebral disk tive nature and considering that the events related spaces (primarily L4-L5 or L5-S1), characterises to it are associated with the activation of the tran - the clinical presentation of the sciatica. In this scription factor NF- κB, ALA’s anti-inflammatory case, the low back pain irradiates to the gluteus action has also been evaluated in terms of its di - and leg. The pain caused by nerve impingement rect inhibitory action against this factor. NF- κB (radicular pain) is associated with numbness, tin - plays a fundamental role in the expression of var - gling, weakness and movement difficulties, par - ious genes involved in inflammatory response ticularly after long periods of sitting. The most and in cell apoptosis processes. Its activation is common cause is the loss of the intervertebral connected to the cell’s exposure to lipopolysac - disks’ cushioning function. The intervertebral charides, inflammatory cytokines (TNF- α and in - disks are essential for absorbing the pressure pro - terleukin-1), growth factors, lymphokines, free duced by spine movements and their degenera - radicals and many other physiological and non- tion greatly reduce spinal mobility and favours physiological stimuli. It has been observed that friction between vertebral bodies and the crush - treatment with ALA causes a down-regulation of ing of the nerve roots passing through the inter - 10,11 NF- κB, which, being a redox-sensitive molecule, vertebral foramens . suffers its oxidative effects. In particular, acute In sensitive/motor radiculopathies, the clinical treatments with ALA have been found to be ef - presentation is characterised by acute pain symp - fective both in inhibiting the degradation of the toms that often require the use of nonsteroidal 2767 M. Costantino, C. Guaraldi, D. Costantino, S. De Grazia, V. Unfer anti-inflammatory drugs (NSAIDs ) or other types CTS is the most common canal syndrome and of painkillers. In these cases, once the acute is caused by an increase in the pressure on the phase has passed, or even in association with the median nerve inside the carpal tunnel; it has a same analgesics, it is useful to introduce sub - prevalence of 5-16% in the general population, stances with an antioxidant and, therefore, anti- with a female:male ratio of 3:1. Pregnant and inflammatory and neurotrophic action. perimenopausal women are particularly at risk, Supplementation with antioxidants and neu - given the water retention related to the hormonal
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