Table 4.

Central mechanisms of knee OA

Study	Male	Female	Findings
Arendt-Nielsen et al., 2010 [5]	Human	Human	Increased central excitability in OA subjects; greater excitability with greater OA pain; lack of correlation between radiographic findings and pain; no discussion of sex differences.
Arendt-Nielsen et al., 2008 [41]	Human	Human	Healthy men show greater decrease in central excitability in response to conditioned pain modulation.
Bajaj et al., 2001 [35]	Human	Human	Hypertonic saline infusion into tibialis anterior shows greater areas of referred pain; no discussion of sex differences.
Baliki et al., 2008 [43]	Human	Human	fMRI shows enhanced activity in thalamus, somatosensory cortex, cingluate cortex, and amygdala in OA patients in response to painful mechanical stimulation; decreased brain activity in response to intra-articular lidocaine.
Ge et al., 2005 [61]	Human	Human	Reduced pain ratings to a second intramuscular injection of glutamate in men compared to women.
Bwilym et al., 2010 [46]	Human	Human	Imaging study shows that atrophy of thalamus in hip OA is reversed by total hip replacement; no sex differences reported.
Gwilym et al., 2009 [48]	Human	Human	Imaging study shows patients with OA have increased activity in brainstem facilitation pathway that is correlated with neuropathic symptoms; no sex differences reported.
Kulkarni et al., 2007 [44]	Human	Human	Reduction in conditioned pain modulation in OA, that is reversed after total joint replacement in pain-free individuals; no sex differences reported.
LeBars et al., 1979 [37]	Rat		Activation of diffuse noxious inhibitory control pathways reduces activity of nociceptive neurons in spinal cord.
Loyd and Murphy, 2006 [62]	Rat	Rat	Review article including 141 references describing sex differences in central pain modulation.
Parks et al., 2011 [45]	Human	Human	fMRI in knee OA shows spontaneous pain activates prefrontal-limbic regions; COX-2 inhibitor decreases spontaneous pain and activity in prefrontal-limbic regions; no sex differences reported.
Sarlani and Greenspan, 2002 [39]	Human	Human	Greater temporal summation to heat and mechanical stimuli in healthy women than men.
Staud et al., 2003 [40]	Human	Human	Conditioned pain modulation is more effective in heathy men than women.
Tousignant-Laflamme and Marchand, 2009 [42]		Human	Menstrual cycle alters conditioned pain modulation in healthy women.
Yarnitsky et al., 2008 [38]	Human	Human	Lower conditioned pain modulation prior to surgery is predictive of postoperative chronic pain.