Comment on "exploring the relationship between pain, cognition, and chronic conditions: insights from the HAALSI study in rural South Africa".

Dear Editor, We read with great interest the article titled “Exploring the relationship between pain, cognition, and chronic conditions: insights from the HAALSI study in rural South Africa” by Dixon et al.1 While previous studies have mainly examined the relationship between pain and cognition in high-income countries, this study addresses a socioeconomically and culturally diverse population residing in rural South Africa. Furthermore, it provides a significant contribution not only by examining the relationship between pain and cognition but also by assessing the potential moderating effects of chronic diseases, such as hypertension, diabetes, HIV, depressive symptoms, and pain management, on this relationship. However, there may be some potential unmeasured confounding factors when interpreting these results. In this study, treatment of pain was classified according to whether the participants received pain medication. While the authors adjusted for pain treatment status, further differentiation of medication classes (e.g., opioids, NSAIDs, gabapentinoids) may clarify whether the treatment type contributes to the observed cognitive effects. A systematic review of opioid use in adults with cancer and chronic non-cancer pain, focusing on older adults, demonstrated that opioid use is associated with impairments in attention, language, orientation, psychomotor function, and verbal working memory, as well as short-term and delayed episodic memory.2 Moreover, a recent study reported that executive function impairment is prevalent among individuals with long-term opioid use.3 A 7-year prospective study examining the effects of NSAID use on cognitive function in older individuals reported no significant association between NSAID exposure and the incidence of dementia or cognitive decline.4 In contrast, a prospective cohort study of 4409 older adults demonstrated that long-term ibuprofen use was associated with a slower rate of cognitive decline.5 Anticonvulsants, such as gabapentin and pregabalin, are also prescribed for pain management and warrant evaluation with respect to cognitive outcomes. A randomized controlled trial in healthy volunteers showed that 12 weeks of pregabalin treatment resulted in negative effects on cognition.6 A recent study of 480 older adults with normal baseline cognition found that initiation of gabapentin was significantly associated with clinically meaningful decline in cognitive and functional status.7 On the other hand, studies have shown that opioid prescriptions are often associated with poorer baseline health status. Therefore, it should be kept in mind that while medication use may directly cause cognitive decline, it may also reflect pain severity or the burden of the comorbidities. The lack of specific types of medications used in pain treatment may limit the interpretation of the mediating mechanisms. Thus, considering the types of drugs used may help identify different mechanisms and potential targets for preserving cognitive function in individuals with chronic pain.