Pregnancy-Induced Analgesia - A Longitudinal Study of DNIC

Pregnancy-induced analgesia has been described in several studies (Gintzler 1980; Sander and
Gintzler 1987; Jarvis et al. 1997). Obvious mechanisms underlying pregnancy-induced
analgesia involve hormonal changes during gestation (Fillingim and Ness 2000). Existing
studies during pregnancy and peripartum have focused on standard characteristics of
nociception, using non-dynamic quantitative sensory testing such as pain threshold/tolerance
or suprathreshold stimuli (Goolkasian and Rimer 1984; Sengupta and Nielsen 1984; Cogan and
Spinnato 1986; Dunbar et al. 1988; Whipple et al. 1990; Shapira et al. 1995; Saisto et al.
2001; Bajaj et al. 2002; Carvalho et al. 2006; Ohel et al. 2007), with its relative
limitations of studying only the afferent nociceptive input produced in the peripheral
nervous system.

The two systems that are of prime importance in pain modulation within the CNS are the
inhibitory system (descending noxious inhibitory control (DNIC)) and the excitatory system,
with the balance of pain being more heavily influenced by the former (Godfrey and Mackey
2008).

The primary aim of this study is to use psychophysical tests to study both the inhibitory
and excitatory pain pathways using the DNIC paradigm and temporal summation longitudinally
during pregnancy, compared to an age-matched control group of non-pregnant women.

We added the In Vitro Fertilization (IVF) sub-population to the PIA study to study them as a
control group (in addition to studying non-pregnant controls and pregnant women). We are
studying this sub population prior to their egg retrieval procedure and a short phone survey
with participants post egg-retrieval. If the subject becomes pregnant, we would recruit them
to enroll in the PIA pregnant population cohort.

Inclusion Criteria:

- Pregnant Cohort: Inclusion criteria for participation are (1) women aged between 18
and 45 yr, (2) nulliparous or ASA physical status class I or II women, (3) singleton
pregnancy, (4) no more than 14 completed weeks gestational age at the time of
enrollment into the study, (5) uncomplicated pregnancy, and (6) delivery planned to
be conducted at UW/Stanford University.

- Non-pregnant Control Cohort: Inclusion criteria for participation are (1) women aged
between 18 and 45 yr, (2) nulliparous or ASA physical status class I or II women, (3)
and not planning on taking oral-contraceptives or carrying a hormonal-coated IUD.

Non-inclusion Criteria:

- Pregnant Cohort: Non-inclusion criteria are (1) multiparous women, (2) non-English
speaking women (subjects have to be able to understand the DNIC procedure and answer
questionnaires), (3) women unable to understand the concept of VNPS at the time of
informed consent (involving mental health issues), (4) a history of anxiety or
depression, or chronic consumption of opiates, antidepressants, or anticonvulsants;
and (5) intake of opioids, acetaminophen, or NSAIDs 48h prior to the psychophysical
test.

- Non-pregnant Control Cohort: Non-inclusion criteria are the same as the Pregnant
Cohort as well as (6) irregular menstrual cycles (defined as < 21 days or > 35 days).

Exclusion Criteria:

- Pregnant Cohort: Exclusion criteria is a pregnancy complicated by preeclampsia or
preterm delivery (< 37 weeks gestation).

- Non-pregnant Control Cohort: Exclusion criteria is development of irregular cycles.