Exposure to the estrogenic pollutant bisphenol A affects pain behavior induced by subcutaneous formalin injection in male and female rats

Brain Res. 2002 May 24;937(1-2):1-7. doi: 10.1016/s0006-8993(02)02446-0.


We investigated the effects of perinatally administered bisphenol A (BPA), an environmental contaminant with estrogenic activity, on formalin-induced nociceptive responses. Male and female offspring of mother rats treated with BPA or oil were cross-fostered after birth to obtain three homogeneous groups: BPA-prenatal, receiving BPA via the placenta; BPA-postnatal, receiving BPA through suckling; OIL, control, from mothers receiving only peanut oil (vehicle). All groups underwent a pain test with s.c. formalin injection (50 microl, 10%) or were sham injected (pricking with a syringe needle) in the dorsal hind paw. They were immediately placed in an open field apparatus where pain responses (licking, flexing and paw-jerk) were recorded for 60 min. Corticosterone, testosterone and estradiol serum levels were determined in blood obtained at the end of the experiment. BPA-prenatal treatment induced an increase in licking duration in females and in flexing duration in both sexes in the first half of the test (0-30 min after formalin injection). BPA-postnatal treatment induced a decrease in paw-jerk frequency in males and females during the second part of the test (30-60 min after formalin injection). Plasma concentrations of corticosterone, estradiol and testosterone did not differ significantly between groups. These results indicate that exposure to BPA modified the activity of neural pathways and/or centers involved in nociception and pain in a sex-related and exposure-related manner.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • Corticosterone / blood
  • Environmental Pollutants / administration & dosage
  • Environmental Pollutants / toxicity*
  • Estradiol / blood
  • Estrogens, Non-Steroidal / administration & dosage
  • Estrogens, Non-Steroidal / pharmacology
  • Estrogens, Non-Steroidal / toxicity*
  • Estrous Cycle
  • Female
  • Formaldehyde / administration & dosage
  • Formaldehyde / toxicity
  • Hyperalgesia / chemically induced*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiopathology
  • Injections, Subcutaneous
  • Lactation
  • Male
  • Maternal-Fetal Exchange
  • Pain / blood
  • Pain / chemically induced
  • Pain / physiopathology*
  • Pain / psychology
  • Phenols / administration & dosage
  • Phenols / pharmacology
  • Phenols / toxicity*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiopathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Punctures
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Somatosensory Disorders / chemically induced*
  • Testosterone / blood


  • Benzhydryl Compounds
  • Environmental Pollutants
  • Estrogens, Non-Steroidal
  • Phenols
  • Formaldehyde
  • Testosterone
  • Estradiol
  • bisphenol A
  • Corticosterone