Sex-dependent roles of prolactin and prolactin receptor in postoperative pain and hyperalgesia in mice

• Published in: Neuroscience Vol. 253; pp. 132 - 141
• Main Authors: Patil, M.J., Green, D.P., Henry, M.A., Akopian, A.N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 03.12.2013; Elsevier
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Disease Models, Animal; Female; Functional Laterality; Fundamental and applied biological sciences. Psychology; Hyperalgesia - genetics; Hyperalgesia - metabolism; Hyperalgesia - pathology; Male; Medical sciences; Mice; Mice, Knockout; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; pain; Pain Measurement; Pain Threshold - physiology; Pain, Postoperative - complications; Pain, Postoperative - genetics; Pain, Postoperative - pathology; Physical Stimulation - adverse effects; post operative model; prolactin; Prolactin - blood; Prolactin - metabolism; prolactin receptor; Rats; Receptors, Prolactin - deficiency; Receptors, Prolactin - metabolism; Sex Factors; sex-dependence; Spinal Cord - metabolism; Time Factors; Vertebrates: nervous system and sense organs; PRL KO; prolactin receptor; PRL-R; pain; prolactin; post operative model; KO; sex-dependence; ANOVA; PRL-R KO; PRL; WT; PRL null-mutant; knock-out; analysis of variance; PRL-receptor; wild-type; PRL-R null-mutant; Nervous system diseases; Rodentia; Sex; Hyperalgesia; Vertebrata; Mammalia; Pain; Adenohypophyseal hormone; Mouse; Prolactin; Animal; Dependence; Models; Biological receptor
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2013.08.035

•Systemic and local up-regulations of incision-induced prolactin are sex-dependent.•Prolactin plays a role in postoperative thermal hyperalgesia in female mice.•Prolactin is involved in postoperative mechanical allodynia in females and males. Although surgical trauma activates the anterior pituitary gland and elicits an increase in prolactin (PRL) serum levels that can modulate nociceptive responses, the role of PRL and the PRL-receptor (PRL-R) in thermal and mechanical hyperalgesia in postoperative pain is unknown. Acute postoperative pain condition was generated with the use of the hindpaw plantar incision model. Results showed endogenous PRL levels were significantly increased in serum, operated hindpaw and spinal cords of male and female rats 24h after incision. These alterations were especially pronounced in females. We then examined the role of the PRL system in thermal and mechanical hyperalgesia in male and female mice 3–168h after plantar incision with the use of knock-out (KO) mice with PRL or PRL-R gene ablations and in wild-type (WT) mice. WT mice showed postoperative cold hyperalgesia in a sex-dependent manner (only in females), but with no effect on heat hyperalgesia or mechanical allodynia in either sex. Studies in KO mice showed no effect of PRL and PRL-R gene ablation on heat and cold hyperalgesia in male mice, while heat hyperlgesia were reduced 3–72h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3–72h post-surgery in both male and female mice. Overall, we found elevated PRL levels in serum, hindpaws and spinal cords after incision, and identify a contributory role for the PRL system in postoperative pain responses to thermal stimuli in females and to mechanical stimuli in both males and females.