Pain and cognitive performance in adults with multiple sclerosis: A systematic review

Introduction: Pain and cognitive dysfunction are separately known to be important manifestations of multiple sclerosis (MS). Although pain is a complex subjective phenomenon with affective and cognitive aspects, it is not known if people with MS reporting pain are at greater risk of reduced performance in objective tests of cognition. The presence or direction of any association remains to be clarified, as do the roles of confounders such as fatigue, medication and mood. Methods: We conducted a systematic review of studies examining the relationship between pain and objectively measured cognition in adults with confirmed MS, according to a pre-registered protocol (PROSPERO 42020171469). We carried out searches in MEDLINE, Embase and PsychInfo. We evaluated the role of potential confounders (medication, depression, anxiety, fatigue and sleep) and described findings by eight pre-specified cognitive domains. Results: 11 studies (n=3714, range 16 to 1890 participants per study) were included in the review. Four studies included longitudinal data. Nine studies identified a relationship between pain and objectively measured cognitive performance. In seven of these studies, higher pain scores were associated with poorer cognitive performance. However, no evidence was available for some cognitive domains. Heterogeneous study methodology precluded meta-analysis. Studies infrequently controlled for the specified confounders. Most studies were judged to be at risk of bias. Discussion: Several studies, but not all, identified a negative relationship between pain severity and objectively measured cognitive performance. Our ability to further characterise this relationship is limited by study design and lack of evidence in many cognitive domains. Future studies should better establish this relationship and delineate the neurological substrate underpinning it.