Pain reduces sexual motivation in female but not male mice

Abstract

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected.

Keywords: motivation; paced mating; pain; sex difference; sexual behavior.

Figure 1.

Reduction of sexual behavior in female but not male mice by inflammatory pain. A, Decreased mounting behavior in a paced mating (F-PM) paradigm when female mice receive zymosan (ZYM) or carrageenan (CARR) injections to the vulva, hind paw, tail, or cheek, compared with uninjected female mice (No Inj.). Bars represent mean ± SEM mounts with (shaded) or without (open) intromissions; n = 7–12 mice/condition. B, Female mice with genital (vulvar; n = 6) or nongenital (combined hind paw, tail, and cheek; n = 23) pain spend less time on the side containing the male in a paced-mating chamber compared with mice receiving uninjected or vehicle injected mice (No Pain; n = 43). Bars represent mean ± SEM time on male side (s). C, No decreases in mounting behavior in an open field (M-OF) when male mice are treated similarly to female mice. Bars as in A; n = 6–10 mice/condition. D, No sex difference in mechanical allodynia produced by hind paw zymosan. Symbols represent mean ± SEM threshold (g) to withdraw from von Frey fibers before (BL) and after (Post-Inj.) bilateral zymosan injection; n = 6 mice/sex. E, No sex difference in facial grimacing produced by hind paw zymosan. Symbols represent mean ± SEM Mouse Grimace Scale (MGS) score before (BL) and after (Post-Inj.) bilateral zymosan injection; n = 4 mice/sex; *p < 0.05, **p < 0.01, ***p < 0.001 compared with vehicle (A, C), No Pain (B), or BL (D, E).

Figure 2.

Reversal of hind paw carrageenan (CARR)-induced reduction in female sexual behavior (all F-PM) by the analgesic, pregabalin (PGB; A), and the libido-enhancing drugs apomorphine (APO; C) and melanotan-II (MT-II; E). The analgesic efficacy of PGB against was confirmed (B), as was the lack of effect on pain by APO (D) and MT-II (F). Bars in A, C, E represent mean ± SEM mounts with (shaded) or without (open) intromissions; n = 4–8 mice/condition. Symbols in B, D, F represent mean ± SEM Mouse Grimace Scale (MGS) score before carrageenan (BL), after carrageenan but before drug (CARR), and after drug (+PGB/+APO/+MT-II); n = 6–8 mice/drug; *p < 0.05, ***p < 0.001 compared with Veh/Veh group (A, C, E) or vehicle (B, D, F); ^•p < 0.05 compared with CARR/Veh group.