title: The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats.
abstract: Considerable evidence exists for sex differences in human pain sensitivity. Women typically report a higher incidence of various painful conditions and report that the conditions are more painful when compared to men. In the present study, we sought to determine whether sex differences in pain sensitivity are observed using a lumbar radiculopathy model of low back pain in the rat and whether removal or alteration of gonadal hormones at specific timepoints can modulate these sex differences. Pubertal and adult male and female Sprague-Dawley rats were castrated 2 or 6 weeks prior to L5 nerve root injury to determine the activational hormonal effects. In a separate study, neonatal male and female Sprague-Dawley rats were either castrated or injected with testosterone, respectively, on postnatal day one to determine the organizational effects of gonadal hormones on L5 nerve root injury-induced behavioral hypersensitivity. Our results demonstrate that there was a statistically significant sex difference in the magnitude of mechanical allodynia and thermal hyperalgesia following experimentally induced radiculopathy in the rat: females demonstrated decreased thresholds to tactile and thermal stimuli as compared to males. Furthermore, the enhanced female hypersensitivity was reversed in pubertal and adult animals ovariectomized 6 weeks, but not 2 weeks prior to L5 nerve root injury. Our results demonstrate that the activational effects of gonadal hormones mediate the enhanced female tactile and thermal hypersensitivity following L5 nerve root injury. These results suggest that manipulation of gonadal hormones may be a potential source for novel therapies for chronic pain in women.
authors.affiliation: Department of Pharmacology and Toxicology, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: LaCroix-Fralish
authors.forename: Vivianne L
authors.initials: VL
authors.lastname: Tawfik
authors.forename: Joyce A
authors.initials: JA
authors.lastname: DeLeo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006358:Hot Temperature; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010147:Pain Measurement / Q000379:methods; D011129:Polyradiculoneuropathy / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013126:Spinal Nerve Roots / Q000293:injuries / Q000378:metabolism*; D014110:Touch / Q000187:drug effects* / Q000502:physiology
chemical_list: D012739:Gonadal Steroid Hormones
references.citation: Horm Behav. 1985 Dec;19(4):469-98
references.pmid: 3910535
references.citation: Eur J Endocrinol. 2003 Mar;148(3):281-92
references.pmid: 12611608
references.citation: Science. 1985 Aug 16;229(4714):671-3
references.pmid: 4023706
references.citation: Lab Anim Sci. 1992 Oct;42(5):508-13
references.pmid: 1460853
references.citation: J Gend Specif Med. 2002 Mar-Apr;5(2):42-7
references.pmid: 11974674
references.citation: Ann N Y Acad Sci. 2003 Dec;1007:263-71
references.pmid: 14993059
references.citation: Fertil Steril. 1998 Apr;69(4):709-13
references.pmid: 9548162
references.citation: Biol Reprod. 2001 Jan;64(1):331-8
references.pmid: 11133691
references.citation: Physiol Behav. 1986;38(6):887-90
references.pmid: 3823208
references.citation: Endocrinology. 1959 Sep;65:369-82
references.pmid: 14432658
references.citation: J Neuroendocrinol. 2000 May;12(5):445-52
references.pmid: 10792584
references.citation: Pain. 1999 Feb;79(2-3):127-33
references.pmid: 10068158
references.citation: Trends Pharmacol Sci. 1991 Apr;12(4):141-7
references.pmid: 2063480
references.citation: Behav Brain Sci. 1997 Sep;20(3):371-80; discussion 435-513
references.pmid: 10097000
references.citation: J Pharmacol Exp Ther. 2002 Feb;300(2):695-701
references.pmid: 11805235
references.citation: Neurosci Lett. 1995 Feb 17;186(2-3):135-8
references.pmid: 7777182
references.citation: Neuroscience. 2000;95(2):559-66
references.pmid: 10658636
references.citation: Neurosci Lett. 1996 Jan 12;203(1):37-40
references.pmid: 8742041
references.citation: Biol Reprod. 2002 Sep;67(3):691-8
references.pmid: 12193373
references.citation: Pharmacol Biochem Behav. 2001 Jan;68(1):99-104
references.pmid: 11274714
references.citation: Neurosci Biobehav Rev. 2000 Jun;24(4):485-501
references.pmid: 10817845
references.citation: J Neurocytol. 2000 May-Jun;29(5-6):327-39
references.pmid: 11424949
references.citation: Front Neuroendocrinol. 1998 Oct;19(4):323-62
references.pmid: 9799588
references.citation: Eur J Neurosci. 2001 Nov;14(9):1436-44
references.pmid: 11722605
references.citation: Clin J Pain. 2003 May-Jun;19(3):168-74
references.pmid: 12792555
references.citation: J Neuroimmunol. 1997 Nov;79(2):163-75
references.pmid: 9394789
references.citation: Brain Res Bull. 2003 Jan 15;59(4):289-92
references.pmid: 12464400
references.citation: EMBO Rep. 2001 Sep;2(9):775-81
references.pmid: 11559590
references.citation: Gynecol Endocrinol. 1997 Dec;11(6):393-7
references.pmid: 9476088
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7093-100
references.pmid: 11416193
references.citation: Brain Res. 2002 Mar 1;929(1):1-9
references.pmid: 11852025
references.citation: Acta Obstet Gynecol Scand. 1988;67(4):307-9
references.pmid: 3051879
references.citation: Brain Behav Evol. 1999;54(1):8-14
references.pmid: 10516400
references.citation: J Neuroimmunol. 2000 Nov 1;111(1-2):77-85
references.pmid: 11063824
references.citation: J Neuroendocrinol. 1990 Feb 1;2(1):1-13
references.pmid: 19210390
references.citation: Brain Res. 1988 Dec 20;475(2):272-82
references.pmid: 2905623
references.citation: Spine (Phila Pa 1976). 2005 Aug 15;30(16):1821-7
references.pmid: 16103850
references.citation: Pain. 1993 Jun;53(3):255-64
references.pmid: 8351155
references.citation: Pain. 1988 Jan;32(1):77-88
references.pmid: 3340425
references.citation: Spine (Phila Pa 1976). 2000 May 15;25(10):1206-17
references.pmid: 10806496
references.citation: J Neurobiol. 2000 Apr;43(1):64-78
references.pmid: 10756067
references.citation: Endocr Rev. 1993 Aug;14(4):459-79
references.pmid: 8223341
references.citation: Physiol Behav. 1977 Jul;19(1):1-6
references.pmid: 11803669
references.citation: Brain Res. 1983 Jul;285(1):39-43
references.pmid: 6883126
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3602-7
references.pmid: 10725383
references.citation: Neurosci Lett. 2000 Mar 24;282(3):197-9
references.pmid: 10717425
references.citation: Brain Res. 2002 Dec 20;958(1):139-45
references.pmid: 12468038
references.citation: Trends Endocrinol Metab. 2003 Jan;14(1):20-7
references.pmid: 12475608
references.citation: J Comp Neurol. 2002 Jun 3;447(3):234-48
references.pmid: 11984818