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Comparative Study
. 2012 Dec;13(12):1224-31.
doi: 10.1016/j.jpain.2012.09.009. Epub 2012 Nov 10.

In vivo and in vitro comparison of female and male nociceptors

Jan Hendrich  1 , Pedro Alvarez, Elizabeth K Joseph, Luiz F Ferrari, Xiaojie Chen, Jon D Levine
Affiliations
Comparative Study

In vivo and in vitro comparison of female and male nociceptors

Jan Hendrich et al. J Pain. 2012 Dec.

Abstract

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.

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Conflict of interest statement

DISCLOSURES

All research was funded by the NIH. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Behavioral experiments show a reproducibly lower mechanical nociceptive threshold in female rats. A. Cutaneous mechanical threshold in skin displays sexual dimorphism. Mechanical threshold was significantly higher in male rats compared to females B. Lower mechanical thresholds were measured in muscle of female rats compared to male. ** represents P<0.01, *** represents P<0.001 (two-tailed t-test).
Figure 2
Figure 2
Action potential properties of female and male nociceptors. A. Representative action potential traces, obtained at rheobase, from female (left) and male (right) nociceptors. The dotted lines represent RMP in both neurons for comparison. B. Resting membrane potential is significantly more hyperpolarized in female neurons than in male neurons. C. However, the membrane potential threshold for action potential generation was not significantly different between the two populations. *** represents P<0.001 (two-tailed t-test)
Figure 3
Figure 3
A. The mechanical threshold of muscle afferents from male and female rats (one tailed t-test). B. The conduction velocity of muscle afferents from male and female rats. t-test, two-tailed. C. Responses of muscle afferents to 10g stimulation from male and female rats. * represents P<0.05 (one-tailed t-test).
See this image and copyright information in PMC

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