PMID- 25807259 OWN - NLM STAT- MEDLINE DCOM- 20160304 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model. PG - e0122924 LID - 10.1371/journal.pone.0122924 [doi] LID - e0122924 AB - Unilateral ligation of the tendon of anterior superficial part of rat masseter muscle (TASM) leads to long-lasting allodynia. Sex differences in peripheral mu-opioid receptor (MOR)-mediated analgesia under persistent myogenic pain are not well understood. In this study, we examined (1) whether locally applied MOR agonists attenuate persistent pain following TASM ligation in a sex dependent manner, (2) whether there are sex differences of MOR expression changes in rat trigeminal ganglia (TG). The effects of MOR agonist, D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate salt (DAMGO), were assessed 14 days after TASM ligation in male, female and orchidectomized (GDX) male rats. MOR mRNA and protein levels in TG 14 days following tendon ligation were also determined. The mechanical thresholds of the injured side were significantly decreased in both male and female rats, from 3 days to 28 days after TASM ligation. A10 mug DAMGO significantly attenuated allodynia in male rats. A 10-fold higher dose of DAMGO was required in female and GDX male rats to produce the level of anti- allodynia achieved in male rats. The level of MOR mRNA in TG from male rats was significantly greater 14 days after TASM ligation compared with the sham-operated male rats, but not from female and GDX male rats. After TASM ligation, males had significantly more MOR immunoreactivity in TG compared to sham-operated males. The MOR levels increased to 181.8% of the sham level in male rats receiving tendon injury. But there was no significant change in female rats receiving tendon injury compared to the sham female rats. Taken together, our data suggest that there were sex differences in the effects of peripheral MOR agonists between male and female rats under TASM ligation developing long-lasting pain condition, which is partly mediated by sex differences in the changes of MOR expressions and testosterone is an important factor in the regulation of MOR. FAU - Bai, Xiaofeng AU - Bai X AD - Associate Professor, Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002. FAU - Zhang, Xia AU - Zhang X AD - Associate Professor, Department of Anesthesiology, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002. FAU - Li, Yanshu AU - Li Y AD - Assistant Professor, Department of Cell Biology, China Medical University, 92 Bei'er Road, Shenyang, P. R. of China, 110001. FAU - Lu, Li AU - Lu L AD - Professor, Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002. FAU - Li, Bo AU - Li B AD - Associate Professor, Department of Oral Anatomy and Physiology, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002. FAU - He, Xiaofan AU - He X AD - Assistant Professor, Department of Anesthesiology, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Analgesics, Opioid) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Opioid, mu) RN - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-) SB - IM MH - Analgesics, Opioid/pharmacology/*therapeutic use MH - Animals MH - Behavior, Animal/drug effects MH - Disease Models, Animal MH - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology/*therapeutic use MH - Facial Pain/*drug therapy/etiology/veterinary MH - Female MH - Hyperalgesia/drug therapy/etiology/pathology MH - Immunohistochemistry MH - Male MH - Orchiectomy MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Receptors, Opioid, mu/agonists/genetics/*metabolism MH - Sex Characteristics MH - Tendon Injuries/complications/pathology MH - Trigeminal Ganglion/metabolism/pathology PMC - PMC4373836 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/03/26 06:00 MHDA- 2016/03/05 06:00 PMCR- 2015/03/25 CRDT- 2015/03/26 06:00 PHST- 2014/08/30 00:00 [received] PHST- 2015/02/16 00:00 [accepted] PHST- 2015/03/26 06:00 [entrez] PHST- 2015/03/26 06:00 [pubmed] PHST- 2016/03/05 06:00 [medline] PHST- 2015/03/25 00:00 [pmc-release] AID - PONE-D-14-39023 [pii] AID - 10.1371/journal.pone.0122924 [doi] PST - epublish SO - PLoS One. 2015 Mar 25;10(3):e0122924. doi: 10.1371/journal.pone.0122924. eCollection 2015.