The Implementation of Stem Cells in Neuropathic Pain Therapy
Chronic neuropathic pain (NP) is considered to be on the rise, especially with the increase in diabetes prevalence among the United States population. NP is pain that results subsequently from a lesion or disease affecting the somatosensory system. NP was described to have a prevalence of 3% to 17% of the adult life population. Overall, 20% to 25% of all chronic pain is associated with NP. Stem cell therapy is a novel method of treatment that is gaining attention. The classic qualities of NP were noted to be burning, shooting, and sharp. NP can be classified as a peripheral or central origin. Trigeminal neuralgia, radiculopathy, polyneuropathy, peripheral nerve injury, and postherpetic neuralgia are all subtypes of peripheral origin NP. On the other hand, subtypes of central origin NP include brain injury, multiple sclerosis, spinal cord injury, and central poststroke pain. All of the previously mentioned subtypes accompany chronic NP that consequently follows the lesion or the disease. The cell-based method of treatment was described by Chakravarthy et al. to be a novel therapeutic approach in the chronic pain associated with neuropathies and degenerative joint disease. Replacement of cells that were previously injured has an impactful role along with delivering trophic factors. MSCs have been shown to be capable of self-renewing and have the potential to differentiate into various cell types including neurons, adipocytes, osteoblasts, and more. As of now, there is no definite treatment of NP syndrome with the concurrent promotion of nervous system repair. Despite that, the novel treatment with the use of stem-cell transplant repairs the nervous system instead of isolated palliation. NP related to disorders including sciatic nerve injury, neuropathies associated with diabetes, and spinal cord injury was demonstrated to be successfully treated with stem cell therapy.
Stem Cell Therapy in Diabetic Neuropathy
The term diabetic neuropathy refers to the occurrence of clinical signs and symptoms resulting from a dysfunction in the peripheral nerves in patients with diabetes mellitus. Diabetic neuropathy is considered to be the most common complication of diabetes mellitus, with a rate of 30% to 50% of affected individuals. Investigations on the utilization of stem cells in diabetic neuropathy were done in three studies conducted on animal models described by Vadivelu et al., where administration of stem cells was through the intramuscular route in the hind leg. MSCs were used due to their ability to differentiate into multiple cell types and their cytokine secretion ability. Moreover, a recent study suggests that MSCs can promote neurotrophic factors. The loss of these factors was reported to be partly attributable to diabetic neuropathy, making the use of these stem cells an advantageous point. One of these studies has conducted a trial with the use of marrow mononuclear cells, due to the easy accessibility to this type of cells. These studies have concluded that improvement was noted in two to 15 weeks duration following the injury. Furthermore, these studies have reported this novel approach as a successful treatment method for neuropathic associated pain. The neurotrophic factors secreted by stem cells were reported to accommodate neuronal protection along with providing neuronal regeneration. Although not the routine treatment for diabetic neuropathy, the use of MSC treatment is indicated in patients with diabetic foot ulcers, acute relapses, intractable symptoms, and critical limb ischemic disease. Thereby, this novel treatment targets both vascular and neural components. The benefit of using MSC therapy is known to be attributed to the modulation of the immune response by the short-term effects of the paracrine and juxtacrine roles rather than by lesion site engraftment of the MSCs as a long-term effect. Generating anti-inflammatory MSCs has been shown to alleviate diabetic neuropathy pain. In a mice treatment module, MSC therapy has been shown to reduce pro-inflammatory cytokine concentrations in the mice’s serum. Prior to and after receiving MSC therapy, the mice were evaluated for painful diabetic neuropathy through two established behavioral assays. Growth factor therapy has shown to be beneficial in diabetic neuropathy due to its ability to promote regeneration of neural tissue and angiogenesis, overall improving nerve function. Bone marrow-derived stem cells were found to produce both angiogenic factors along with neurotrophic growth factors, supplementing selective cells in order to sequent the neuronal regeneration process, and having a more beneficial effect than the growth factor treatment.
Stem Cell Therapy in Trigeminal Neuralgia
Trigeminal NP encompasses variable states of diagnosis, this includes trauma resulting in maxillofacial NP, odontalgia which is atypical, and burning mouth syndrome. Trigeminal NP is considered to be a localized pain. Thereby, its patient population forms an ideal group to investigate the innovative novel therapy. NP is associated with poor response to over-the-counter analgesia and opioids, along with moderate pain relief in 40% of patients in response to anticonvulsant medications and tricyclic antidepressants. MSCs were found to exert anti-inflammatory impacts via cytokine secretion, combatting the ongoing inflammation manifesting as the NP. The previously proposed hypothesis has been studied on animal models with trigeminal NP showing a notable reduction in the inflammatory symptoms and promising outcomes. Sacerdote et al. conducted a study on an animal model with hind paw NP. He reported that utilizing MSCs derived from adipose tissue resulted in the reduction of interleukin-1b pro-inflammatory cytokine and increased levels of IL-10, which is an anti-inflammatory cytokine in injured nerve tissue. A notable decrease in mechanical allodynia and the accompanied thermal hyperalgesia was noticed. MSC therapy administration was previously evaluated and well established to be safe in trials involving both humans and animal models. No abnormal transformations were reported on the cranial nerve-associated nerve physiology. Also, there were no changes in the distribution area of sensation for the trigeminal nerve branches (V2 and V3) and lastly, no notable changes in the injection site. In addition, there were no abnormal reports on motor nerve abnormalities of the face or the jaw involving the seventh cranial nerve or the trigeminal nerve’s motor branch respectively.
Stem Cell Therapy in Spinal Cord Injury
Two experimental studies were conducted on mouse models to study spinal cord injury treatment with the use of stem cell therapy. Embryonic stem cell oligosphere culture derivatives such as oligodendrocyte progenitor cells were selected to be utilized by one study group to cause remyelination in the lesioned nerve leading to NP inhibition. Neuregulin was downregulated afterward through an interfered RNA. Thereafter, the myelinating process was noted to be reduced along with an increment in the allodynia functional measures. The other study used nanoparticles in correlation with co-cultured human stem cells that are derived from adipose tissue. Both in vivo and in vitro studies resulted in an increase in the expansion and self-renewing process of the administered stem cells. This was especially noted in the GABAergic neurons with a reported significant decrease in the inflammatory cells and the inflammatory mediators along with allodynia improvement after an interval duration of four weeks.
Precision Pain Care and Rehabilitation has two convenient locations in Richmond Hill – Queens and New Hyde Park – Long Island. Call the Richmond Hill office at (718) 215-1888, or (516) 419-4480 for the Long Island office, to arrange an appointment with our Interventional Pain Management Specialist, Dr. Jeffrey Chacko.
