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.
Highlights
Pain constitutes a multidimensional experience that includes cognitive, affective, and sensory characteristics in response to noxious stimuli
We developed our proposal of the beneficial effects of intranasal OT administration for pain alleviation in aging based on an integrative review of currently parallel lines of research
In consideration of literature supporting OT’s analgesic effects, as reviewed we propose that intranasal OT constitutes a promising candidate for the management of chronic pain, via mechanisms that impact brain morphology in regions associated with chronic pain
Summary
Pain constitutes a multidimensional experience that includes cognitive, affective, and sensory characteristics in response to noxious stimuli. The specific relationships between chronic pain, brain morphology, and OT in the context of aging are currently not understood This focused narrative review addresses an existing gap in the literature by synthesizing studies that support associations of chronic musculoskeletal pain, given its high prevalence, with brain morphology in regions that constitute critical targets of intranasal OT administration in aging. Our model integrates the associations between chronic muskuloskeletal pain, brain structure (e.g., gray matter morphology and white matter integrity), and the endogenous OT system [e.g., circulatory levels, OT receptor (OXTR) genotype and expression, OT binding site locations] within the context of aging and proposes that the three may interact to increase age-related chronic pain susceptibility Based on these interactions, we propose intranasally administered OT as a treatment for chronic pain in older individuals constitutes a promising research direction. This proposal is based on evidence of a significant overlap between brain regions relevant in pain processing with brain regions identified as crucial targets of the OT system (Figure 2)
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