Caspases, or cysteine-aspartic acid proteases, are a family of cysteine proteases, which play an essential role in apoptosis (programmed cell death), necrosis and inflammation. Translocation of NFkβ to the nucleus has been reported to result in activation of the endogenous proteolytic enzyme system caspases [69]. Joseph & Levine [71] suggested that activity in signaling pathways that ultimately lead to apoptosis plays a critical role in the generation of neuropathic pain, before death of sensory neurones becomes apparent. Activator and effector caspases, defining components of programmed cell death signalling pathways, also contribute to pain-related behaviour in animals with small fibre peripheral neuropathies. The death receptor ligand, tumour necrosis factor α, and its downstream second messenger, ceramide, also produce pain-related behaviour via this mechanism.
- The first step in treating alcoholic neuropathy includes stopping alcohol use altogether.
- In general, it takes years for alcoholic neuropathy to develop, so a long-standing history of heavy alcohol use is typical.
- A person should speak with a doctor if they are experiencing any symptoms of alcoholic neuropathy or if they are concerned about their alcohol use.
- However, the limitations of those studies include the lack of the possibility to measure the amount of vitamin B1 in the serum; further, patients who were involved in the study have received an unrefined form of the supplement.
- You may need to be sedated for more than a week until the alcohol withdrawal symptoms go away.
- Injection of (S)-2,6-diamino-N-[[1-(oxotridecyl)-2-piperidinyl]methyl] hexanamide dihydrochloride (NPC15437), a selective PKC inhibitor, once a day for a week after 4 weeks of ethanol treatment.
The Symptoms of Alcoholic Neuropathy and Treatment Options
A review of the human literature implicates nutritional deficiencies, most often thiamine deficiency, that are common in alcoholic patients, as commonly accompanying complicating factors in the development of this neuropathy. Persons with alcoholism may consume smaller amounts of essential nutrients and vitamins and/or exhibit impaired gastrointestinal absorption of these nutrients secondary to the direct effects of alcohol. In general, the nerves in lower limbs were more affected than the upper limbs [3, 37–39].
Management of alcoholic neuropathy
A smaller number of publications do attribute thiamine deficiency, but generally speaking these studies were older or of lower quality evidence [4, 6, 30, 58, 76, 77]. Of all the deleterious effects of excessive alcohol consumption, neuropathy is the most common. The true incidence of alcoholic neuropathy in the general population is unknown, and figures vary widely depending on the definition of chronic alcoholism and the criteria used to detect and classify neuropathy.
How to Prevent Alcoholic Neuropathy
Moreover, phosphorylated PKC was significantly increased in the spinal cord following chronic ethanol consumption. These findings constitute direct evidence that spinal PKC plays a substantial role in the development and maintenance of an ethanol-dependent neuropathic pain-like state in rats. Females, generally tend to drink less alcohol, are better abstainers, and present the smaller probability of the development of alcohol-related diseases [127, 128].
Alcoholic Neuropathy Treatment & Management
Physical therapy and orthopedic appliances (such as splints) may be needed to maintain muscle function and limb position. Motor nerves are the nerves responsible for all voluntary skeletal and somatic movement such as moving the leg or arm. This is a summary of independent research carried out at the NIHR Sheffield Biomedical Research Centre (Translational Neuroscience). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
- It’s important to speak with a healthcare professional if you experience any symptoms of peripheral neuropathy.
- An 8 week, randomized, multicentre, placebo-controlled, double-blind study compared the effect of benfotiamine alone with a benfotiamine complex (Milgamma-N) or placebo in 84 alcoholic patients.
The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine (vitamin B1). A deficiency of vitamin B1 in chronic alcoholics can be due to inadequate dietary intake, reduced capacity for hepatic storage, inhibition of intestinal transport and absorption or decreased formation of the active coenzyme form. In an animal study, it has been found that chronic alcohol consumption in rats resulted in a significant depletion in thiamine diphosphate (TDP), the active coenzyme form of thiamine. Supplementation with benfotiamine significantly increased concentrations of TDP and total thiamine compared with supplementation with thiamine HCl [96]. An 8 week, randomized, multicentre, placebo-controlled, double-blind study compared the effect of benfotiamine alone with a benfotiamine complex (Milgamma-N) or placebo in 84 alcoholic patients.
The US National Library of Medicine (NLM) warns that around 50 percent of long-term heavy drinkers will suffer from alcoholic neuropathy. Clinical features of alcoholic peripheral neuropathy develop slowly, extending over alcohol neuropathy stages a period of months and include abnormalities in sensory, motor, autonomic and gait functions. Painful sensations with or without burning quality represent the initial and major symptom of alcoholic neuropathy [2, 4].
Computed tomography (CT) scans showed that among alcohol-dependent patients, the brain volumes were reduced to increase the volume of cerebrospinal fluid; these changes were induced in females in less time [135, 136]. The mouse model of the injection of β-estradiol in males resulted in higher activity of cytosolic alcohol dehydrogenase (ADH), microsomal aniline hydroxylase (ANH), and aldehyde dehydrogenase (ALDH) which are crucial in ethanol metabolism [138]. Female mouse with injected testosterone showed the decreased activity of cytosolic isoform of ALDH which implies that those enzymes are sensitive to estrogen and testosterone and alcohol metabolism is greater in females. Ethanol and its toxic metabolites affect neural metabolism including metabolic activities in the nucleus, lysosomes, peroxisomes, endoplasmic reticulum, and cytoplasm [104].
- It is likely to get worse if the person continues to use alcohol or if nutritional problems are not corrected.
- Alcohol abuse treatment might lead to a resolution of neuropathic pain and alleviation of its symptoms.
- Call for an appointment with your provider if you have symptoms of alcoholic neuropathy.
- It has previously been considered in relationship to nutritional, especially thiamine, deficiencies seen in alcoholics.
This suggests that these pathways are potential targets for novel pharmacological agents for the treatment of inflammatory as well as neuropathic pain [71]. Based on these studies, it can be determined that there is a high rate of peripheral neuropathy amongst chronic alcohol abusers. It also appears that the addition of NCS may improve the identification of alcohol-related peripheral neuropathy. Electrical nerve stimulation sends a small electrical current through the skin and nerves that can help with sensitivities and pain, making it an option for treatment. Alternative therapies like chiropractic care, body manipulation, acupuncture, meditation, and massage therapy can be helpful in managing pain and symptoms of alcoholic polyneuropathy. The main goal of a treatment program for alcoholic polyneuropathy is to improve quality of life and offer relief from symptoms.
Parameters measured included vibration perception in the great toe, ankle and tibia, neural pain intensity, motor function and paralysis, sensory function and overall neuropathy score and clinical assessment. Although benfotiamine therapy was superior to Milgamma-N or placebo for all parameters, results reached statistical significance only for motor function, paralysis and overall neuropathy score. The reason for better results in the benfotiamine alone group than in the Milgamma-N group, despite the fact that the benfotiamine dosage was equivalent, is not completely understood. The authors hypothesized that vitamins B6 and B12 might have competed with the effects of vitamin B1 in the Milgamma-N group [97].