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. Author manuscript; available in PMC: 2022 Apr 1.
Published in final edited form as: Pain. 2021 Apr 1;162(4):1116–1125. doi: 10.1097/j.pain.0000000000002116

Figure 7. HMWH attenuates LMWH hyperalgesia in ovariectomized female rats and in female rats treated with ODN antisense to GPR30 mRNA.

Figure 7.

A. Ovariectomy. Female rats underwent ovariectomy 14 days prior to administration of HMWH (1 μg/5 μL) or vehicle (5 μL), injected intradermally on the dorsum of the hind paw, 10 min after LMWH (1 μg/5 μL) was injected in the same site. Magnitude of mechanical hyperalgesia, evaluated over 30 min after intradermal LMWH, in ovariectomized females was attenuated by HMWH (in contrast to intact females (see Figure 2)) (F(1,10)=33.37, **p=0.0073, when the LMWH-induced hyperalgesia is compared between HMWH- and vehicle-treated groups 10 min after intradermal LMWH; *p=0.0143, when the LMWH-induced hyperalgesia is compared between HMWH- and vehicle-treated groups 15 min after intradermal LMWH; **p=0.0018, when the LMWH-induced hyperalgesia is compared between HMWH- and vehicle-treated groups 20 min after intradermal LMWH; ***p=0.0003, when the LMWH-induced hyperalgesia is compared between HMWH- and vehicle-treated groups 30 min after intradermal LMWH; two-way repeated-measures ANOVA followed by Holm-Šídák multiple comparison test). n=6 paws per group.

B. GPR30 ODN-treated. Female rats were treated daily with spinal intrathecal injections of antisense or mismatch ODN (120 μg/20 μL) to GPR30 mRNA, for 3 consecutive days. On the fourth day, HMWH (1 μg/5 μL) was injected intradermally, on the dorsum of the hind paw, and 10 min later, LMWH (1 μg/5 μL) was injected in the same site. The magnitude of mechanical hyperalgesia, evaluated over 30 min after intradermal LMWH, was significantly attenuated in rats treated with antisense, compared to mismatch, GPR30 ODN (F(1,10)=33.59, **p=0.0071, when the LMWH-induced hyperalgesia is compared between GPR30 antisense ODN- and GPR30 mismatch ODN treated groups 10 and 30 min after intradermal LMWH; *p=0.0142, when the LMWH-induced hyperalgesia is compared between GPR30 antisense ODN and GPR30 mismatch ODN treated groups 15 min after intradermal LMWH; ****p<0.0001, when the LMWH-induced hyperalgesia is compared between GPR30 antisense ODN- and GPR30 mismatch ODN-treated groups 20 min after intradermal LMWH; two-way repeated-measures ANOVA followed by Holm-Šídák multiple comparison test). n=6 paws per group.

C. Ovariectomy plus 17β-estradiol. A group of female rats that underwent ovariectomy received 17β-estradiol replacement, 14 days prior to administration of HMWH (1 μg/5 μL) or vehicle (5 μL), injected intradermally on the dorsum of the hind paw, 10 min after LMWH (1 μg/5 μL) was injected in the same site. The magnitude of mechanical hyperalgesia was evaluated over 30 min after intradermal LMWH. Ovariectomized females with 17β-estradiol replacement show similar response to gonad intact female group, HMWH did not attenuate LMWH hyperalgesia (F(1,10)=1.471, p=0.2531; two-way repeated-measures ANOVA followed by Holm-Šídák multiple comparison test). n=6 paws per group.