Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model

Xiaofeng Bai; Xia Zhang; Yanshu Li; Li Lu; Bo Li; Xiaofan He

doi:10.1371/journal.pone.0122924

Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model

PLoS One. 2015 Mar 25;10(3):e0122924. doi: 10.1371/journal.pone.0122924. eCollection 2015.

Authors

Xiaofeng Bai¹, Xia Zhang², Yanshu Li³, Li Lu⁴, Bo Li⁵, Xiaofan He⁶

Affiliations

¹ 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.
² Associate Professor, Department of Anesthesiology, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.
³ Assistant Professor, Department of Cell Biology, China Medical University, 92 Bei'er Road, Shenyang, P. R. of China, 110001.
⁴ Professor, Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.
⁵ Associate Professor, Department of Oral Anatomy and Physiology, School of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.
⁶ Assistant Professor, Department of Anesthesiology, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.

Abstract

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 μg 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics, Opioid / pharmacology
Analgesics, Opioid / therapeutic use*
Animals
Behavior, Animal / drug effects
Disease Models, Animal
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / therapeutic use*
Facial Pain / drug therapy*
Facial Pain / etiology
Facial Pain / veterinary
Female
Hyperalgesia / drug therapy
Hyperalgesia / etiology
Hyperalgesia / pathology
Immunohistochemistry
Male
Orchiectomy
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Receptors, Opioid, mu / agonists
Receptors, Opioid, mu / genetics
Receptors, Opioid, mu / metabolism*
Sex Characteristics
Tendon Injuries / complications
Tendon Injuries / pathology
Trigeminal Ganglion / metabolism
Trigeminal Ganglion / pathology

Substances

Analgesics, Opioid
RNA, Messenger
Receptors, Opioid, mu
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-

Grants and funding

These studies were supported by grants from the National Natural Science Foundation of China (81400530) and Technology Foundation for Selected Overseas Chinese Scholar, Ministry of Personnel of China ([2014]240). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.