This study looks at the differences in inflammatory mediators in gallbladder tissue between
males and females and the possibility that these differences contribute to a higher
perception of post-operative pain in females following laparoscopic cholecystectomy.
A patient's gender is a strong and significant predictor for substantial differences in
clinical outcomes such as postoperative pain, analgesic use, and surgical complications
(gangrenous gallbladder, empyema of the gallbladder, gallbladder perforation, and conversion
to open surgery) following laparoscopic cholecystectomy (Bingener et al., 2002; Bingener et
al., 2003; Uchiyama et al., 2006). Although females present for laparoscopic cholecystectomy
more frequently (76% of the cases); the prevalence of surgical complications during
cholecystectomy is higher in men, most frequently because of inflammation or deterioration
of the gallbladder (Bingener et al., 2002; Bingener et al., 2003; Stefanidis et al., 2006).
Post-operatively, however, females report significantly greater pain scores and require
larger amounts of analgesics (Uchiyama et al., 2006), suggesting that although surgeries are
completed with fewer problems, females still report more post-operative pain. Sex-related
differences in pain thresholds and tolerance to thermal, pressure, and electrical stimuli in
experimental pain models indicate that pain differences are not solely due to psychosocial
distinctions between the sexes (Riley et al., 1998).
There are multiple physiological differences between males and females; however,
considerable evidence implicates estrogenic sex hormones as critical factors in
sex-dependent differences in pain (see review by Fillingim and Ness, 2000). It is possible
that estrogens alter inflammatory mediator profiles in the gallbladder, which subsequently
increase sensitization of visceral neurons innervating the gallbladder, resulting in
increased pain in females. The first portion of this study will extend the association of
patient sex with clinical outcomes to determine whether circulating and/or local estrogen
levels correlate with differences in peri-operative morbidity, including intra-operative
complications, conversion to open cholecystectomy, postoperative pain, inadequate wound
healing, intra-abdominal infection, disability and mortality.
Previous studies have demonstrated that the cytokines TNFalpha and IL-1beta alter the
sensitivity of sensory neurons and increase nociception (Opree and Kress, 2000). To
determine whether estrogen levels alter the profile of inflammatory mediators within the
gallbladder and result in an increase in nociceptive thresholds in females, we will
correlate circulating and/or local levels of estrogens with the amount of inflammatory
mediators present within laparoscopically excised gallbladder biopsies. Patients who meet
the inclusion criteria will be recruited from University Hospital in San Antonio.
Inflammatory mediators, including the cytokines IL-1beta, TNFalpha, IL-8, IL-6, IL-10, and
IL-12p70 will be assayed from interstitial fluid of biopsies from the fundus and
infundibulum of the gallbladder. Biopsies will be classified according to clinical
assessment prior to surgery to control for expected differences in inflammatory mediators in
acute versus chronic cholecystitis.
The immediate effects of this research will be to clearly delineate whether estrogens are
predictive of improved clinical outcomes following surgery and to determine whether these
sex hormones correlate with altered production of inflammatory mediators in the gallbladder.
- Males or Non-pregnant females
- Between ages 18-90
- Pregnant Females within six months of surgery
- Individuals below age 18 or above age 90
- Previous topical or systemic corticosteroid use within three months of surgery date
- sign and symptoms of neuropathy or self-reported history of diseases or treatments
known to be associeated with neuropathy
- signs and symptoms of altered immune system or self-reported diseases or treatments
known to be associated with altered immune function