Sex-dependent roles of prolactin and prolactin receptor in postoperative pain and hyperalgesia in mice
•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...
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| Published in | Neuroscience Vol. 253; pp. 132 - 141 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Amsterdam
Elsevier Inc
03.12.2013
Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0306-4522 1873-7544 1873-7544 |
| DOI | 10.1016/j.neuroscience.2013.08.035 |
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| Abstract | •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. |
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| AbstractList | Highlights • 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 3-168 h 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 3-72 h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3-72 h 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.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 3-168 h 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 3-72 h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3-72 h 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. •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. 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 24 hours 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 3-168 hours 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 3-72 hours post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3-72 hours 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. 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. 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 3-168 h 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 3-72 h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3-72 h 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. |
| Author | Patil, M.J. Green, D.P. Akopian, A.N. Henry, M.A. |
| AuthorAffiliation | 3 Department of Endodontics, University of Texas Health Science Center at San Antonio, TX, 78229, USA 1 Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX, 78229, USA 2 Department of Physiology, University of Texas Health Science Center at San Antonio, TX, 78229, USA |
| AuthorAffiliation_xml | – name: 3 Department of Endodontics, University of Texas Health Science Center at San Antonio, TX, 78229, USA – name: 1 Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX, 78229, USA – name: 2 Department of Physiology, University of Texas Health Science Center at San Antonio, TX, 78229, USA |
| Author_xml | – sequence: 1 givenname: M.J. surname: Patil fullname: Patil, M.J. organization: Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX 78229, USA – sequence: 2 givenname: D.P. surname: Green fullname: Green, D.P. organization: Department of Physiology, University of Texas Health Science Center at San Antonio, TX 78229, USA – sequence: 3 givenname: M.A. surname: Henry fullname: Henry, M.A. organization: Department of Endodontics, University of Texas Health Science Center at San Antonio, TX 78229, USA – sequence: 4 givenname: A.N. surname: Akopian fullname: Akopian, A.N. email: Akopian@UTHSCSA.edu organization: Department of Pharmacology, University of Texas Health Science Center at San Antonio, TX 78229, USA |
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| Keywords | 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 |
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| Snippet | •Systemic and local up-regulations of incision-induced prolactin are sex-dependent.•Prolactin plays a role in postoperative thermal hyperalgesia in female... Highlights • Systemic and local up-regulations of incision-induced prolactin are sex-dependent. • Prolactin plays a role in postoperative thermal hyperalgesia... Although surgical trauma activates the anterior pituitary gland and elicits an increase in prolactin (PRL) serum levels that can modulate nociceptive... |
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| SubjectTerms | 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 |
| Title | Sex-dependent roles of prolactin and prolactin receptor in postoperative pain and hyperalgesia in mice |
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