Older and Better: A Narrative Review of Successful Aging and Adaptation to Pain in Late Life.

"Invariably, the self-assessed QoL was far better than I, as a physician, would have anticipated from the diseases and disabilities that you reported." -Ben Eiseman, MD, based on a survey of his octogenarian Yale University classmates. BACKGROUND: Chronic pain control is a high priority for the elderly; it is one of the most frequently encountered medical problems in this group. Chronic pain affects 60%-75% of people aged 65 years and older. Chronic pain's prevalence is even higher in those living in assisted living or nursing homes. Based on epidemiological data, the prevalence of chronic pain is directly proportional to age and is especially so in women. At least one in 3 patients over age 65 report significant ongoing pain that is often inadequately treated. Despite this high prevalence of chronic pain in older persons, aging research sheds light on how this suffering may be reduced. Healthy aging is not an oxymoron. Successful aging and adaptation to chronic pain involve similar medical, temperamental, behavioral, and cultural factors. Older patients with chronic pain face well-documented cultural bias, fear, and clinical pessimism; but adaptive coping is a realistic expectation. OBJECTIVES: This narrative review aims to summarize the available literature on strategies used by older persons to optimize adaptation to late-life pain. STUDY DESIGN: This is a narrative review of a PubMed literature search 1947 to March 4, 2024. METHODS: A PubMed literature search covering years 1947 to March 4, 2024 was performed using permutations of the search terms pain, chronic pain, persistent pain, aging, elderly, and coping. Relevant articles were also obtained from careful review of the references in articles identified in the search. RESULTS: I summarized the available literature on strategies used by older persons to optimize adaptation to late-life pain. There are distinct differences between older persons and younger persons in the strategies they use to cope with chronic pain. Furthermore, I identified significant overlap between strategies and actions used by older persons to cope with pain and those strategies and actions used to successfully adapt to the aging process; these commonalities demonstrate a linkage of these adjustment processes and have clinical utility. Also presented are 2 cases that demonstrate the relevance of these factors for treating elderly patients with chronic pain. LIMITATIONS: The literature search was limited to PubMed, which excluded psychology databases. CONCLUSIONS: Chronic pain is common in the elderly and is not adequately treated. Data indicate that older persons can benefit from guidance toward distinct attitudes and actions they can employ to cope with persistent pain. Epidemiologic and aging literature describe attitudes and behaviors that facilitate health and wellbeing during aging. Data from gerontology and from research on chronic pain in elderly patients converge upon factors that are common to better adaptation to both aging and late-life pain. I describe these common factors, which I categorize as treatment-factors, traits, attitudes, and actions. Two cases are presented to demonstrate these concepts.

Medication-induced mood disorders following epidural steroid injections in patients with pain: A case series.

Key Clinical Message: Medication-induced mood disorders following epidural steroid injections are possible therefore should be disclosed to the patient. Abstract: Medication-induced mood disorders have been rarely reported following epidural steroid injections (ESI). This case series presents three patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for substance/medication-induced mood disorder after an ESI. In considering a candidacy for ESI, the rare but significant, side effects of psychiatric side effects should be disclosed to patients.

Is there an association between lumbosacral epidural lipomatosis and lumbosacral epidural steroid injections? A comprehensive narrative literature review.

BACKGROUND: Exogenous systemic steroid exposure is a well-established risk factor for spinal epidural lipomatosis (SEL), however the association between lumbosacral epidural steroid injections (LESIs) and lumbosacral epidural lipomatosis (LEL) is generally regarded as poorly understood. Our objective was to investigate the rationale and the evidence implicating LESI(s) as a potential cause of LEL as well as the evidence related to use of LESI(s) as a potential pain relieving treatment option for radicular pain in the setting of LEL. METHODS: PubMed, Embase, Google Scholar, OVID were searched from inception until April 2021. Three investigators identified literature that provided original descriptive patient clinical data attributing the development/progression of LEL to LESI(s) or described the use of LESI(s) as a pain relieving modality for radicular pain in the setting of LEL. RESULTS: Fourteen publications were included for review. Overall, the current level of evidence is of low-quality. There are significant methodological gaps on this subject matter and many studies do not account for confounding variables independently associated with LEL. CONCLUSIONS: This review has identified substantial limitations in the literature regarding that which is truly known regarding LESI(s) and LEL, as well as conservative management overall. To provide a well-rounded perspective, we synthesized literature as it pertains to: 1) current knowledge regarding SEL, notable associations and potential implications for corticosteroid exposure; 2) corticosteroid exposure and lipoatrophy; 3) current management recommendations for SEL and 4) areas for future focus. Although LESI(s) have been associated with LEL in the literature, presently due to a lack of rigorous, high-quality studies, the presence or absence of an independent causal relationship between LESI(s) and LEL cannot be stated with confidence.

Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia.

We have previously shown clinical activity of a mammalian target of rapamycin (mTOR) complex 1 inhibitor in Waldenstrom macroglobulinemia (WM). However, 50% of patients did not respond to therapy. We therefore examined mechanisms of activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR in WM, and mechanisms of overcoming resistance to therapy. We first demonstrated that primary WM cells show constitutive activation of the PI3K/Akt pathway, supported by decreased expression of phosphate and tensin homolog tumor suppressor gene (PTEN) at the gene and protein levels, together with constitutive activation of Akt and mTOR. We illustrated that dual targeting of the PI3K/mTOR pathway by the novel inhibitor NVP-BEZ235 showed higher cytotoxicity on WM cells compared with inhibition of the PI3K or mTOR pathways alone. In addition, NVP-BEZ235 inhibited both rictor and raptor, thus abrogating the rictor-induced Akt phosphorylation. NVP-BEZ235 also induced significant cytotoxicity in WM cells in a caspase-dependent and -independent manner, through targeting the Forkhead box transcription factors. In addition, NVP-BEZ235 targeted WM cells in the context of bone marrow microenvironment, leading to significant inhibition of migration, adhesion in vitro, and homing in vivo. These studies therefore show that dual targeting of the PI3K/mTOR pathway is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR signaling cascade, such as WM.

Novel therapeutic agents in Waldenström's macroglobulinemia.

Within the past few years, major advances in the preclinical and clinical testing of novel therapeutic agents have occurred in Waldenström's macroglobulinemia (WM). These include agents that target the PI3K/Akt/mTOR pathway, PKC pathways, NF-kB signaling pathway, as well as tyrosine kinases and histone deacetylase inhibitors. In this review, we summarize the current understanding of the clinical development of these agents in WM.