Table 3 Identified gaps in sex/gender differences in knee OA

Gap 1

Are there sex differences in nociceptor innervation of the OA joint?

Gap 2

Do sex hormones modify knee joint nociceptor activity?

Gap 3

Do nociceptors innervating the OA joint respond differently to inflammatory stimuli between the sexes?

Gap 4

Does peripheral opioid peptide and receptor upregulation after knee OA differ between the sexes?

Gaps related to the central nervous system

Gap 5

Are there sex differences in processing of nociceptive information from knee in the central nervous system in the healthy or diseased knee?

Gap 6

Are there sex differences in brain activation patterns associated with knee OA pain?

Gap 7

Do sex hormones modulate central neuronal activity associated with nociception in the healthy or diseased knee?

Gap 8

Are there sex differences in OA patients for measures of temporal summation (central excitability) and conditioned-pain modulation (central inhibition)?

Gaps related to psychosocial factors

Gap 9

Are there sex differences in psychosocial variables in OA such as depression, anxiety, self-efficacy, pain catastrophizing, and fear of pain?

Gaps that encompass all factors

Gap 10

Are different pharmacologic and non-pharmacologic strategies needed to address treatment of adverse psychosocial variables between sexes?

Gap 11

Might effective pain management strategies to reduce pain in OA differ between women and men?

Gap 12

What is the influence of age on sex differences?