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Review Article | DOI: https://doi.org/10.31579/2767-7370/112
1 Former, Associate Professor, S.D.N.B. Vaishnav College for Women, Chennai,
2 Former, Director Grade Scientist, Centre for Cellular and Molecular Biology, Hyderabad, India
*Corresponding Author: PD Gupta, Former, Director Grade Scientist, Centre for Cellular and Molecular Biology, Hyderabad, India.
Citation: K Pushkala and PD Gupta, (2024), Efficacy of Faecal transplant technique (FMT) to manage Neuropathic pain, J New Medical Innovations and Research, 5(6); DOI:10.31579/2767-7370/112
Copyright: © 2024, PD Gupta. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 07 July 2024 | Accepted: 20 July 2024 | Published: 08 August 2024
Keywords: somatosensory; dysesthesia; neuropathic pain; faecal transplant technique
Disorders of the somatosensory nervous system or neuropathic pain are associated with abnormal sensations called dysesthesia. Somatic symptom disorder is diagnosed when a person has a significant focus on physical symptoms, such as pain, weakness or shortness of breath, to a level that results in major distress and/or problems functioning. There is no specific treatment available, only intended to help control symptoms and to allow the person to function as normally as possible. Lately, FMT treatment showing some promising results.
Neuropathic pain or nerve pain (neuralgia) is a particular type of shooting, stabbing or burning sensation caused by damage or injury either to the nerves that send messages to your brain to signal pain, or to the brain itself may be worse at night, can be mild or severe but difficult to treat. At times a feeling is as sharp and sudden as an electric shock, very sensitive to touch or cold and also experience pain due to touch that would not normally be painful, such as something lightly brushing the skin. Neuropathic pain is characterized by abnormal hypersensitivity to stimuli (hyperalgesia) and nociceptive responses to non-noxious stimuli (allodynia) [1]. The conditions and the pathophysiological states that determine the onset of neuropathic pain are heterogeneous, such as metabolic disorders, viral infections and autoimmune diseases affecting the central nervous system (CNS). Nerve pain can affect any nerve in our body, but it commonly affects some nerves more than others such as post-herpetic pain, trigeminal pain, occipital pain and pudendal pain [2].
Nerve pain is associated with Sciatica ( pressure on the nerves of the lower back that causes pain down your leg accompanied by pins and needles, numbness or weakness in your leg), Fibromyalgia ( a chronic pain syndrome associated with burning or aching pain in different parts of your body due to unknown cause but triggered by emotional distress and poor sleep and genetic factors too), peripheral neuropathy developed by the peripheral nerves (nerves that that connect the brain and spinal cord to the rest of the body) are damaged due to diabetes, autoimmune diseases and other conditions. In addition an injury to brain, spine or nerves, poor blood supply to your nerves, heavy alcohol use, phantom pain after an amputation, vitamin B12 or thiamine (vitamin B1) deficiency, medicines, infections such as shingles and HIV/AIDS, multiple sclerosis, diabetes, stroke, cancer and its treatment with radiation, surgery, or chemotherapy, trapped nerves, such as in carpal tunnel syndrome could be also the causal factor for the prognosis of neuropathic pain especially fibromyalgia [3].
Diabetic neuropathy (DN) is painful if sugar is not under control ultimately resulting in the increase of morbidity and mortality. It often characterized by loss of sensation, pain, numbness, gait disorder, even amputation. The pathological mechanism involved in the development of DN remains unknown in spite of high prevalence rate. In the present scenario early detection of DN can only be achieved by assessing the nerve fibers, limited treatment with certain non-specific drugs with side effects and possibility of abuse [4].
Fibromyalgia affects up to 2% of general population. However, fatigue, chronic widespread pain non-refreshed sleep, mood disturbance and cognitive impairment such as forgetfulness, concentration difficulties, loss of vocabulary and mental slowness, among others are common, and have an important influence on quality of life that is challenging to diagnose and difficult to treat. In recent past this disorder is also associated with altered intestinal microbiota, suggesting that modulating gut microbiota could be an effective therapeutic treatment [5].
Global burden
Incidence and prevalence of neuropathic pain are difficult to estimate due to the lack of consensus on the definition of neuropathic pain globally. According to a systematic review of epidemiology of chronic pain, prevalence between 3% and 17% was recorded, while the incidence was calculated in 3.9–42.0/100,000 person-years for post-herpetic neuralgia; 12.6–28.9/100,000 person-years for trigeminal neuralgia; 15.3–72.3/100,000 person-years for peripheral diabetic neuropathy (PDN), and 0.2–0.4/100,000 person-years for glossopharyngeal neuralgia. Moreover, neuropathic pain was more prevalent among women (60.5% of patients), reached a peak at 50–64 years of age, and was more frequently reported by manual workers, as well as among people from rural areas.
Management of Neuropathic pain
Most of the available treatments for neuropathic pain have moderate efficacy and present side effects that limit their use. Natural compounds have been investigated for their efficacy for the management of neuropathic pain similar to other diseases.
Several clinical studies suggest the efficacy of Cannabis sativa with around 100 cannabinoids was found to modulate neuropathic pain. Xie et al. [6] evaluated the effect of Puerarin a compound isolated from Radix puerariae, a potent antioxidant and anti-inflammatory agent used in traditional Chinese medicines for the myocardial and cerebral ischemia treatment [6]. Similarly, Qin, et al. in the same year investigated the analgesic effects of Gastrodin, a bioactive constituent of the traditional Chinese herbal medicine, in peripheral neuropathy [7]. Antihyperalgesic effect of the D-limonene (LIM-monocyclic monoterpene extracted from oranges and lemons) alone or complexed with β-cyclodextrin (βCD) was evaluated in an animal model of fibromyalgia. Kandhare and colleagues showed from their studies the possible involvement of the Azadirachta indica (AI), a tree of the Meliaceae family, in the treatment of peripheral neuropathy. The study results gave a promising hope for the possibility of the neuroprotective effect of AI for the treatment of neuropathic pain [8].
First-line treatments are based on the use of antidepressants and antiepileptic drugs. second- and third-line treatment are generally recommended to use Opioids due to their adverse related effects, while the strong opioids, oxycodone, and morphine are used in the third-line treatment [9].
FMT and neuropathy
Wealth of data now indicates that the gut microbiota has a connection with the central nervous system (CNS) and also participates in the regulation of cognition and pain, in addition to regulating peripheral and central sensitization [10]. The lipid metabolites of the gut microbiome has been linked to peripheral immune regulation, visceral pain, chemotherapy-induced pain), and fibromyalgia.
Development of Visceral hypersensitivity in patients is due to reduction in the abundance of butyrate‐producing Lachnospiraceae, which is beneficial for the intestinal barrier. The members of this family of bacteria utilize lactate and acetate to produce butyrate via the butyryl‐CoA or acetate CoA transferase pathways or the butyrate kinase pathway. Roseburia hominis, one such member proved to be a potential probiotic for treating stress‐induced visceral hypersensitivity. In addition, by verifying the beneficial effect of butyrate‐producing R. hominis on WAS rats, the results suggest that specific bacterial taxa or their metabolites are associated with visceral sensitivity and colonic barrier function. Roseburia has been considered to be a potential indicator of intestinal health, since alleviation of visceral hypersensitivity and increased caecal butyrate concentration after Roseburia administration. Prevotellaceae and Coriobacteriaceae increased, whereas that of Peptococcaceae decreased significantly after stress treatment. Prevotellaceae is reportedly involved in several intestinal diseases [11]. The literature survey indicates that only few studies have reported on the clinical application of microbes in neurogenic disorders.
The gut microbiota in diabetic neuropathy patients differ significantly from that of healthy controls [12]. Bäckhed F. et al. [12]. endorsed that FMT increased the insulin resistance from conventionally reared germ-free mice. Later Vrieze A. et al., [13] found an increase (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota, six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients. The authors anticipated that intestinal microbiota could be developed as therapeutic agents to increase insulin sensitivity in humans also. Subsequently, Shen S., et al. [14] suggested that when FMT was performed on the appellate mice, the pain would be restored, indicating that the gut microbiota has an effect on neuropathic pain. Castelli V., et al. [15]. from another study found that probiotics alleviated the characteristics of paclitaxel-induced neuropathic pain in vitro, although their efficacy is dependent on the type of neuropathic pain. For instance, Lactobacillus Reuteri or Bifidobacterium were not effective against the neuropathic pain induced by chronic compression injury in rats.
Limited references are available for the efficacy of FMT on DN patients though they all gave the clue for positive results. Xu, HM. et al., [16] from their study reported a case of FMT to reach palliation of diabetic neuropathic pain and glycemic homeostasis.
Researchers showed from more than 8,000 gut microbiome profiles sampled from people in eight different countries abnormal changes in 19 bacterial species that are linked to increased risk of developing type 2 diabetes. Out of the 19 gut bacteria species identified, five were linked with type 2 diabetes alone and 14 with prediabetes and type 2 diabetes [17]. As reported in Nature Medicine, examples of the bacteria present at abnormal levels were higher levels of Clostridium bolteae and depleted Butyrivibrio crossotus. Low levels of the latter have been linked to obesity. This study included microbiomes sampled from 8,117 people (54
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