The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

LaCroix-Fralish ML, Michael L LaCroix-Fralish, Tawfik VL, Vivianne L Tawfik, DeLeo JA, Joyce A DeLeo
Pain · 2005 · vol. 114(1-2) , pp. 71–80 · doi:10.1016/j.pain.2004.12.006 · PMID:15733633 · PMC1361499
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L5 nerve root injury in rats induces greater tactile and thermal hypersensitivity in females, an effect mediated by activational gonadal hormones that is reversed by pubertal or adult ovariectomy.

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This study investigated sex differences in pain sensitivity following lumbar nerve root injury using a rat model of low back pain. Researchers compared male and female Sprague-Dawdy rats, employing castration or testosterone injection at various developmental stages to isolate organizational and activational effects of gonadal hormones. The results showed that females exhibited significantly greater mechanical allodynia and thermal hyperalgesia than males, an enhanced hypersensitivity that was reversed by ovariectomy performed six weeks prior to injury but not two weeks prior. These findings indicate that adult-level gonadal hormones actively mediate increased pain sensitivity in females after nerve injury. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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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.
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The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats - Michael L. LaCroix-Fralish - Vivianne L. Tawfik - Joyce A. DeLeo 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.

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MeSH descriptors

Gonadal Steroid Hormones Hot Temperature Polyradiculoneuropathy Sex Characteristics Spinal Nerve Roots Touch Animals Animals, Newborn Female Gonadal Steroid Hormones Male Orchiectomy Ovariectomy Pain Measurement Pain Measurement Polyradiculoneuropathy Pregnancy Rats Rats, Sprague-Dawley Spinal Nerve Roots

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