Article

Sex similarities and differences in pain-related periaqueductal gray connectivity

Linnman, Clas^a,b,*,1; Beucke, Jan-Carl^b,c,1; Jensen, Karin B.^b,c; Gollub, Randy L.^b,c; Kong, Jian^b,c

Author Information

^aP.A.I.N. Group, McLean Hospital, Belmont, MA, USA

^bAthinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA

^cDepartment of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA

^*Corresponding author at: Department of Psychiatry, Massachusetts General Hospital, Suite 2106, 75 13th Street, Charlestown, MA 02129, USA. Tel.: +1 857 284 2816.

E-mail: [email protected]

¹The first two authors contributed equally to this study.

E-mail: [email protected]

Submitted May 13, 2011; revised October 7, 2011; accepted November 3, 2011.

Pain 153(2):p 444-454, February 2012. | DOI: 10.1016/j.pain.2011.11.006

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Abstract

Summary

Pain induces changes in the functional connectivity between the periaqueductal gray and the cingulate, and, in men more than women, connectivity changes to the amygdala.

This study investigated sex similarities and differences in pain-related functional connectivity in 60 healthy subjects. We used functional magnetic resonance imaging and psychophysiological interaction analysis to investigate how exposure to low vs high experimental pain modulates the functional connectivity of the periaqueductal gray (PAG). We found no sex differences in pain thresholds, and in both men and women, the PAG was more functionally connected with the somatosensory cortex, the supplemental motor area, cerebellum, and thalamus during high pain, consistent with anatomic predictions. Twenty-six men displayed a pain-induced increase in PAG functional connectivity with the amygdala caudate and putamen that was not observed in women. In an extensive literature search, we found that female animals have been largely overlooked when the connections between the PAG and the amygdala have been described, and that women are systematically understudied with regard to endogenous pain inhibition. Our results emphasize the importance of including both male and female subjects when studying basic mechanisms of pain processing, and point toward a possible sex difference in endogenous pain inhibition.