title: Chronic Pain in the Elderly: The Case for New Therapeutic Strategies.
abstract: BACKGROUND
  Elderly patients in general exhibit a higher incidence of chronic and neuropathic pain conditions. This group poses a particular clinical challenge due to age-related pharmacokinetic and pharmacodynamic issues, comorbid conditions, and polypharmacy, as well as frailty and cognitive decline. Poor control of pain has consistently been identified as an issue for older people. The identification of safe and efficacious treatments for chronic pain remains a critical public health concern, especially considering the progressive increase of the world's elderly population.
  
  
  OBJECTIVE
  This narrative review deals with the principal alterations of the somatosensory system together with changes in non-neuronal cells in the course of aging. The possibility to control chronic pain based on an innovative strategy which addresses non-neuronal cell dysregulation control will also be discussed.
  
  
  METHODS
  Narrative review.
  
  
  RESULTS
  Peripheral nerves display functional, structural, and biochemical changes with aging that mainly involve Aδ fibers. Alteration in the responses to heat pain in the middle insular cortex and primary somatosensory cortex are also observed in the elderly. In general, pain threshold increases with age while the threshold of pain tolerance remains unchanged or decreases. Additionally, other important modifications of the pain perception system in this age group consist in a clear reduction in the descending inhibitory capacity with an associated increase in central sensitization. Furthermore, different changes concern immune system cells, such as mast cells and microglia, that with age show an increase in their sensitivity to noxious stimuli and a decreased capability to be regulated by homeostatic endogenous systems. Since these cells are the primary interlocutors for pain neurons, their alterations lead to changes that promote persistent neuroinflammation, thereby impacting pain neuronal cell functionality.
  
  
  CONCLUSIONS
  This review is not an exhaustive review for the current evidence supporting the role of immune cells in influencing pain somatosensory neuron functions. It is also important to stress the small number of studies designed to determine the efficacy and safety of anti-pain therapies in elderly patients.
  
  
  CONCLUSIONS
  Non-neuronal cells of immune system origin such as microglia and mast cells, along with astrocytes, are capable of influencing pain somatosensory neuron functions. These nervous system non-neuronal cells may thus be viewed as innovative targets for persistent pain control. Among therapies aiming at preserving the functionality of non-neuronal cells, palmitoylethanolamide, with its high efficacy/risk ratio, may be an excellent co-treatment for the ever-growing elderly population with chronic pain.
authors.affiliation: Department of MESVA, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Paladini
authors.affiliation: Scientific Information and Documentation Center, Epitech Group, 35030 Saccolongo, Padua, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Fusco
authors.affiliation: Department of Medicine, Medical School, University of Perugia, 05100 Terni, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Coaccioli
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Skaper
authors.affiliation: University of L'Aquila, and Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Varrassi
mesh_terms: D000368:Aged / Q000706:statistics & numerical data*; D000369:Aged, 80 and over; D059350:Chronic Pain / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D009437:Neuralgia / Q000453:epidemiology / Q000628:therapy; D059408:Pain Management / Q000639:trends*