Molecular and Cellular Mechanisms of Neuropathic Pain in Aging

Neuropathic pain is a chronic condition that tends to worsen over time, leading to a significant decline in patients' quality of life. The elderly population is disproportionately affected by this burden, as evidenced by the high prevalence of this condition in such a demographic. While previous studies have demonstrated the involvement of various signaling pathways critical to neuropathic pain, the relationship between aging and the onset or persistence of this condition has been overlooked. Greater focus was placed on the efficacy and tolerability of medications, as well as new protocols for assessing pain in patients with cognitive impairment, with less regard for reasons underlying the increased susceptibility of elderly individuals to pain. This Review thus aims to summarize the contributions of aging to neuropathic pain, covering weakened repair function, increased intracellular calcium signaling, enhanced oxidative stress, dysfunctional brain function, impaired descending inhibition, alterations in the innate immune cell population, and the effects of comorbidity caused by aging. A better understanding of these aspects could drive new treatment options thereby yielding better outcomes for elderly patients in pain.