Musculoskeletal Pain and Brain Morphology: Oxytocin’s Potential as a Treatment for Chronic Pain in Aging

Abstract

Chronic pain disproportionately affects older adults, severely impacting quality of life and independent living, with musculoskeletal pain most prevalent. Chronic musculoskeletal pain is associated with specific structural alterations in the brain and interindividual variability in brain structure is likely an important contributor to susceptibility for the development of chronic pain. However, understanding of age-related structural changes in the brain and their associations with chronic musculoskeletal pain is currently limited. Oxytocin (OT), a neuropeptide present in the periphery and central nervous system, has been implicated in pain attenuation. Variation of the endogenous OT system (e.g., OT receptor genotype, blood, saliva, and cerebrospinal fluid OT levels) is associated with morphology in brain regions involved in pain processing and modulation. Intranasal OT administration has been shown to attenuate pain. Yet, studies investigating the efficacy of OT for management of chronic musculoskeletal pain are lacking, including among older individuals who are particularly susceptible to the development of chronic musculoskeletal pain. The goal of this focused narrative review was to synthesize previously parallel lines of work on the relationships between chronic pain, brain morphology, and OT in the context of aging. Based on the existing evidence, we propose that research on the use of intranasal OT administration as an intervention for chronic pain in older adults is needed and constitutes a promising future direction for this field. The paper concludes with suggestions for future research in the emerging field, guided by our proposed Model of Oxytocin's Anagelsic and Brain Structural Effects in Aging.

Age and intranasal oxytocin effects on trust-related decisions after breach of trust: Behavioral and brain evidence.

“…The literature discusses that age-related differences in socioemotional proficiency (Hoppmann, et al, 2018; Mather & Carstensen, 2005; Sze et al, 2012) and associated neurobiological processes, including changes in brain structure and function (Ebner et al, 2016; Horta et al, 2019), gonadal hormones (Ebner et al, 2015; Grace et al, 2018; MacDonald, 2013; MacDonald & Feifel, 2013), baseline oxytocin levels (Plasencia et al, 2019), and gene expression (Quintana et al, 2019), could explain why oxytocin intervention does not exert the same effects in younger and older adults’ brains and behaviors. The examination of mechanisms involving age variations is a necessary and promising future direction for research on oxytocin (Ebner, Maura, Macdonald, Westberg, & Fischer, 2013; Ebner et al, 2015, 2018; Huffmeijer, van Ijzendoorn, & Bakermans-Kranenburg, 2013; Lussier, Cruz-Almeida, & Ebner, 2019; Sannino, Chini, & Grinevich, 2017), including in the context of trust-related decision making and prosociality.…”

“…Finally, interactions between endogenous (naturally occurring) oxytocin levels on functional effects of exogenous oxytocin are not yet well understood (see also Lussier et al, 2019, for a discussion). We did not find an effect of endogenous plasma oxytocin on trust-related decision making or evidence of an interaction with intranasal oxytocin administration.…”

“…al., 2019), could explain why oxytocin intervention does not exert the same effects in younger and older adults' brains and behaviors. The examination of mechanisms involving age variations is a necessary and promising future direction for research on oxytocin (Ebner, Maura, Macdonald, Westberg, & Fischer, 2013;Ebner et al, 2015Huffmeijer, van Ijzendoorn, & Bakermans-Kranenburg, 2013;Lussier, Cruz-Almeida, & Ebner, 2019;Sannino, Chini, & Grinevich, 2017), including in the context of trust-related decision making and prosociality. Insula activity was not modulated by age or oxytocin.…”

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial

“…In particular, various pathways to central and peripheral targets via intranasal OT administration have been proposed for the modulation of social cognition (Quintana et al 2015 ; Martins et al 2020 ). OT has also been considered for the treatment of conditions such as autism spectrum disorder (ASD) (Yamasue 2016 ), pain (Rash et al 2014 ; Lussier et al 2019 ), schizophrenia (MacDonald and Feifel 2012 ), and drug addiction (Sarnyai and Kovács 1994 ). Intranasal OT has also recently received attention as a candidate for improving function across social and emotional domains in late adulthood (Huffmeijer et al 2013 ; Ebner et al 2014 ).…”

Intervenções não medicamentosas na promoção da saúde

“…As regiões mais prevalentes são os membros inferiores e tronco. Aproximadamente 82% das dores musculoesqueléticas ocorrem nesses segmentos, podendo variar de acordo com o tipo de profissão e comorbidades relacionadas (FAORO et al, 2018;LUSSIER et al, 2019;CARDOSO et al, 2009). Com o envelhecimento populacional, a carga musculoesquelética das doenças está aumentando, especialmente em países em desenvolvimento (BLYTH; NOGUCHI N. 2017).…”