Study of Pain Perception Between Males and Females Following Laparoscopic Cholecystectomy
Study of Pain Perception Between Males and Females Following Laparoscopic Cholecystectomy
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.
Inclusion Criteria:

 -  Males or Non-pregnant females

 -  Between ages 18-90

 Exclusion Criteria:

 -  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