Chronic pain, analgesic prescribing, and cognitive decline

Background: 

Chronic pain, typically defined as pain lasting more than 3 months, is the leading cause of disability worldwide [1]. Chronic pain, which increases substantially with age, is consistently associated with lower cognitive function and it is increasingly associated with elevated rates of cognitive decline and dementia [2]. The mechanisms connecting chronic pain to cognitive decline remain poorly understood.

Opioids and other analgesics, which are commonly prescribed to manage pain, are often proposed as potential contributors to cognitive decline, possibly via their adverse effects on respiratory, cardiovascular and inflammatory systems as well as their direct impact on the central nervous system [2]. The evidence linking analgesics to cognitive outcomes is mixed. Some studies find that certain types of analgesics, particularly opioids, exacerbate cognitive decline. Others find no significant association or even potential protective effects [3,4]. These studies are often small, examine short-term analgesic use, and focus on only one type of analgesic at a time, despite the common long-term and combined use of multiple analgesics in the management of chronic pain. 

Chronic pain is complex. It can manifest as a symptom of disease (chronic secondary pain) and as a disease in its own right (chronic primary pain) and is shaped by, and in turn influences, a wide range of sociodemographic, biological and psychological factors. Despite this complexity, chronic pain is often treated as one homogenous group in research. The mixed evidence linking analgesic use and cognitive decline may partly stem from variations in cognitive trajectories arising from differences in the nature of the chronic pain, the patterns of pain prescribing, as well as the interactions between pain and analgesic drugs with other factors such as comorbidities, genetic risk factors, epigenetic modifications, and alterations in brain structure.