In vivo and in vitro comparison of female and male nociceptors

While it is generally accepted that women have lower pain thresholds for diverse forms of noxious stimuli, the mechanistic basis for this sexual dimorphism in nociceptive pain remains to be elucidated. We confirmed, in the rat, that females have lower cutaneous mechanical nociceptive thresholds and established a similar sexual dimorphism in muscle. To determine if a peripheral mechanism underlies this sexual dimorphism in pain threshold, we compared biophysical properties of cultured dorsal root ganglion (DRG) neurons that innervated the gastrocnemius muscle in female and male rats. DRG neurons from female rats, which innervated the gastrocnemius muscle, had a more hyperpolarized resting membrane potential. To determine if this was associated with a higher mechanical nociceptive threshold, in contradiction to our working hypothesis, we compared the function, in vivo, of nociceptive afferents innervating the gastrocnemius muscle in male and female rats. C-fiber nociceptors innervating muscle in female rats had higher mechanical thresholds than those in males. Other response characteristics of these nociceptors were not significantly different. Thus, both in vitro and in vivo electrophysiology experiments support the idea that lower mechanical nociceptive threshold in females may be due to sexual dimorphism in central nervous system mechanisms, a difference large enough to overcome an opposing difference in peripheral pain mechanisms.

Perspective: This article unifies in vivo and in vitro electrophysiology with behavioral data examining the differences in mechanical nociceptive threshold between male and female rats. The data provide a novel perspective on the peripheral and behavioral outcomes of noxious mechanical stimulation.