A Review on Stem Cell Therapy For Facial Neuropathic Pain

Pain is a complicated concept with physiological, neurobiological and psychological aspects which makes it a different experience to any individual. Normally, pain occurs as an answer to a tissue damaging condition. Face and oral cavity contain many important sensory centers which are required for survival. Nervous responses in head and face are mainly performed by the trigeminal nerve (TN). TN divides to three major branches: v1 is known as ophthalmic division and is responsible for upper structures such as nose, orbit, forehead and sculp V2 branch is associated with maxillary senses and eventually, the mandibular sensation is related to v3 or mandibular division.

First division trigeminal postherpetic neuralgia, burning tongue/ mouth syndrome, phantom tooth pain, persistent idiopathic facial pain, neurovascular odontalgia, persistent dentoalveolar pain disorder, neuropathic trigeminal pain, and neuropathic orofacial pain are all explained by trigeminal nerve condition.

Orofacial pain occurs due to divergent origins including dental, mucosal, musculoskeletal, neurovascular, and neuropathic pain . Odontogenic and periodontal conditions are the most prevalent causes of pain.

Psychological conditions can also initiate habits like bruxism and clenching that might lead to chronic orofacial pains. Based on epidemiological investigations, nearly 25% of the population have reported nondental orofacial pain which 11% of them is chronic orofacial pain. In addition, different studies indicated a prevalence of 6.9-10% for neuropathic pain. Patients suffering from chronic orofacial pain (COFP) indicate deteriorated factors associated to quality of life. The International Association for the Study of Pain describes neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”.

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Neuropathy has an incoherent essence although its lesions can be classified in four major categories: focal or multifocal lesions of the peripheral nervous system, generalized lesions of the peripheral nervous system (polyneuropathies), lesions of the central nervous system, and complex neuropathic disorders.

Neuropathic pain, regardless of its chronic nature, is more severe than other types of chronic pains which is because of increased exacerbation of physical and mental aspects of life quality. Pain features an exceptionally complex nature. These days, there are no conclusive drugs for neuropathic pain management, however, some pharmacological drugs are used to relief the pain such as lidocaine, lamotrigine, acetaminophen, dextromethorphan, carbamazepine, gabapentin, valproic acid, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants. Molecular methods including gene therapy and viral vector for biological anti-nociceptive molecules transfer are treatment plans that have been introduced to achieve pain relief. As mentioned above, pain is a response to a tissue injury, therefore, the repair mechanism is related to the proliferation and differentiation of cells that leads to restoring the function. The exact mechanism is not understood yet but it can be associated with nonhemopoietic progenitor cells in damaged tissue which can induce the reparative potential.

Recent studies indicate that stem cell transplantation can lead to decelerate or even ceasing of different nervous system injury models, therefore, neuropathic pain as a neurodegenerative condition can also response to stem cell therapy stem cells are undifferentiated cells which are able to differentiate to different tissues cells. In an adult body, stem cells can be found in various tissues, although their number is limited, they have a major role in repairing and renewing damaged tissues. Adult stem cells depending on their origins are divided into placenta and umbilical cord stem cells, hematopoietic stem cells, bone marrow-derived mesenchymal stem cells (MSCs), and adipose-derived MSCs. Mesenchymal stem cells (MSC) have a mesodermal origin and can be found in adult bone marrow followed by skeletal muscle cells, blood, fat, vascular and urogenital systems and connective tissues all over the body. they are one of the regenerative-potent cells that can act as undifferentiated cells and also multilineage differentiation as a result of a cell signaling system.

These particular stem cells have several advantages including stable genetic and phenotype, easy harvest method, and compatibility to various delivery procedures and formulations from laboratory to bedside. There are two remarkable features that make MSCs a good choice for stem cell therapy first, the capability of migration to damaged tissue sites and second, possessing significant immunosuppressive mechanisms that can be used for both positive autologous and heterologous transplants. Therefore, MSCs are considered to be appropriate for allografts since they do not have a considerable Class 2 histocompatibility molecule and only have a low Class 1. This indicates that MSCs are not immunologically protected and can only be known as ‘immune evasive.’ However, many studies indicate that MSCs are not immunogenic and do not induce alloreactivity, but instead they can escape from cytotoxic T-cells and natural killer-cells lysis.

stem cells ‘potential to release neurotrophic factors, as well as providing a cellular basis to substitute the damaged neural cells, is the key idea of using stem cells toward neuropathic pain. These abilities make them perfect candidates for modulating and potentially reversing irresolvable neuropathic pain. In the developing of neuropathic pain both the neurotrophic factors and the neuroinflammatory cascades triggered by immune and glial cells play a significant role. If the equilibrium is broken between both factors, and the inflammatory side is prominent, neuropathic pain occurrence is more likely.

Stem cells inhibit the threat of the inflammatory cytokines with Secretion of neurotrophic factors and anti-neuroinflammatory cytokines which have a neuroprotective as well as regenerative effect. Nerve growth factor (NGF) and neurotrophic glial cell line-derived factor are particular neurotrophic components, helping the damaged nerve to repair itself by function preservation, regeneration increase and neural plasticity adjustment as a reaction to harm. In conclusion, neuropathic pain is a complicated disease affecting quality of life without any actual treatment. The treatment plan used for this disease usually includes variety of painkillers which do not solve the problem and is highly expensive to the health system. Stem cell therapy is a new approach to achieve the definite cure for pain in the future.