Purpose: Chronic pain affects more than 80% of individuals with spinal cord injury (SCI), profoundly impairing mobility, rehabilitation, and quality of life. Conventional pharmacologic and non-pharmacologic treatments often fail to achieve adequate relief. Spinal cord stimulation (SCS) has emerged as a potential neuromodulatory therapy for neuropathic pain; however, its role in SCI remains insufficiently defined. Patients and methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered with PROSPERO (CRD42024541622). Comprehensive searches of PubMed, Embase, Web of Science, and the Cochrane Library were performed through April 2024. Eligible studies evaluated SCS for chronic pain in adults with SCI and reported validated pain or patient-reported outcomes. Screening, eligibility assessment, and data extraction were performed in duplicate. Risk of bias and certainty of evidence were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and the MethodologicAl STandards for Epidemiological Research (MASTER) tool. Results: From 1064 records, 10 studies involving 43 participants met inclusion criteria. Most were case reports or small case series, with one prospective cohort study. All studies reported pain improvement after SCS using heterogenous outcome formats; minor adverse events were reported in 3 studies, and the remaining 7 studies reported none. The overall certainty of evidence was rated very low due to small sample sizes, heterogeneity in study design, and methodological limitations. Three ongoing clinical trials evaluating SCS for pain in SCI were also identified. Conclusion: Preliminary, very low-certainty evidence indicates that SCS may be a promising option for chronic pain after SCI, with limited reported complications in the available literature. Higher-quality studies are required to confirm benefit, characterize risks, and guide patient selection and programming. Prospero Registration Number: CRD42024541622.

Spinal cord stimulation (SCS) is a promising therapy for the management of spinal cord injury. Following SCS, this patient experienced a significant reduction in pain and decreased spasticity, which ultimately led to improved upper extremity function.

Epitalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide developed from the amino-acid composition of epithalamin, a chemically distinct pineal-derived polypeptide preparation. This narrative review evaluates the mechanistic, preclinical, and human evidence for synthetic epitalon in the context of regenerative and longevity medicine, while considering epithalamin studies separately as historical context. PubMed and Google Scholar were searched through 22 September 2026, with primary experimental and clinical studies prioritized and evidence appraised by study design, model, sample size, intervention, outcomes, safety reporting, and independent replication. Epitalon has been reported to modulate telomere-maintenance pathways, circadian and neuroendocrine function, oxidative stress, and cellular aging markers. Preclinical studies suggest biological activity, but direct evidence in musculoskeletal disease models is lacking. Human evidence is limited to small physiological or biomarker studies and an older controlled study in retinitis pigmentosa; no adequately powered randomized trial has established therapeutic efficacy. Pharmacokinetic, dose-ranging, and long-term safety data remain inadequate, while oncologic, immunogenicity, product-quality, and regulatory uncertainties following a 2026 FDA advisory review remain unresolved. Epitalon is therefore biologically active but clinically unproven, and further standardized pharmacologic, safety, and disease-specific studies are needed before clinical translation.

Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed from the amino-acid composition of epithalamin, a pineal-derived polypeptide preparation. Although historically related, the two preparations are chemically distinct and their evidence should not be considered interchangeable. This narrative review examines the mechanistic, preclinical, and human evidence for epitalon, with epithalamin studies considered separately as historical context. The strongest mechanistic evidence for epitalon involves telomerase activation and telomere elongation in human cell lines. These findings were independently replicated in 2025, with telomere extension occurring through hTERT/telomerase upregulation in normal cells and alternative lengthening of telomeres in cancer cell lines.[1] Preclinical studies have also reported age-dependent neuroendocrine effects, antioxidant-associated activity, and tissue-protective effects. In female mice, epitalon did not increase mean lifespan but increased maximum lifespan by 12.3%.[2] Human epitalon evidence remains limited to small physiological or biomarker studies and an older report in retinitis pigmentosa; no adequately powered randomized trial has established therapeutic efficacy.[1,3,4] Historical epithalamin studies have reported neuroendocrine, antioxidant, cardiovascular, and longevity-associated outcomes, but these findings cannot be directly extrapolated to epitalon. Human pharmacokinetic, dose-ranging, and dedicated prospective safety studies remain unavailable, while telomere-maintenance effects raise theoretical but unresolved questions regarding long-term oncologic safety. FDA reviewed epitalon free base and acetate through the 2026 PCAC compounding process, which does not constitute therapeutic approval. [5] Overall, epitalon demonstrates biologically relevant activity but remains clinically unproven. Independent replication, pharmaceutical characterization, pharmacokinetic and safety studies, disease-specific preclinical models, and appropriately designed human trials are needed before its role in regenerative or longevity medicine can be established.

Epitalon is a synthetic tetrapeptide derived from the amino acid composition of Epithalamin, a polypeptide extract derived from the bovine pineal gland. Current preclinical evidence suggests that Epitalon may activate telomerase by upregulating human telomerase reverse transcriptase (hTERT). In aged primates, Epitalon has also been associated with restoring evening melatonin synthesis and circadian cortisol rhythms. It has also been shown to enhance endogenous antioxidant defenses, including the activity of superoxide dismutase (SOD) and glutathione peroxidase. These mechanisms may be relevant to the future of regenerative medicine, as dysregulation of these pathways has been independently implicated in common musculoskeletal conditions, including osteoarthritis, disc degeneration, osteoporosis, and impaired tissue repair. In female mice, although Epitalon did not affect mean lifespan, the maximum lifespan increased by 12.3%. Evidence suggests that it may preserve retinal integrity in hereditary retinitis pigmentosa without reported adverse effects.[1] No human randomized controlled trials, pharmacokinetic studies, or registered trials of Epitalon have been reported at the time of this publication. The related polypeptide preparation Epithalamin, however, does have limited human studies in elderly patients. Epithalamin treatment was associated with a reduced incidence of cardiovascular and musculoskeletal disease, as well as decreased mortality over 6-8 years of follow-up.[2] This review synthesizes the available evidence on Epitalon in the context of regenerative medicine.